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You are here: Home / Publications / Bibliographies and Resource Guides / Canine Models in Biomedical Research, 1990-2009  / Musculoskeletal System  Printer Friendly Page
Canine Models in Biomedical Research,  1990-2009
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Musculoskeletal System

Allen, M.R. and D.B. Burr (2008). Changes in vertebral strength-density and energy absorption-density relationships following bisphosphonate treatment in beagle dogs. Osteoporosis International 19(1): 95-9. ISSN: 0937-941X.
NAL Call Number: RC931.O8
Abstract: We aimed to determine the effects of bisphosphonates on mechanical properties independent of changes in bone density. Our results show that at equivalent bone densities, vertebrae from beagles treated with bisphosphonate have equivalent bone strength and reduced bone energy absorption compared to those from untreated animals. INTRODUCTION: Assessing the relationship between mechanical properties and bone density allows a biomechanical evaluation of bone quality, with differences at a given density indicative of altered quality. The purpose of this study was to evaluate the strength-density and energy absorption-density relationships in vertebral bone following a one-year treatment with clinical doses of two different bisphosphonates in beagle dogs. METHODS: Areal bone mineral density (aBMD) and compressive mechanical properties (ultimate load and energy absorption) were assessed on lumbar vertebrae from skeletally mature beagle dogs treated with vehicle (VEH), alendronate (ALN), or risedronate (RIS). Relationships among properties were assessed using analyses of covariance. RESULTS: Neither treatment altered the strength-density relationship compared to VEH, suggesting increases in vertebral strength with bisphosphonate-treatment are explained by increased density. The energy absorption-density relationship was altered by ALN, resulting in significantly lower energy absorption capacity at a given aBMD compared to both VEH (-22%) and RIS (-14%). CONCLUSIONS: These data document that after adjusting for increased aBMD, vertebrae from animals treated with bisphosphonates have similar strength as those from untreated animals. Conversely, when adjusted for increased aBMD, alendronate treatment, but not risedronate treatment, significantly reduces the energy required for vertebral fracture, indicative of an alteration in bone quality.
Descriptors: bone density drug effects, bone density conservation agents pharmacology, diphosphonates pharmacology, lumbar vertebrae drug effects, alendronate pharmacology, compressive strength, dogs, etidronic acid analogs and derivatives, etidronic acid pharmacology, models, animal.

Arican, M., M. Ortatatli, K. Yigitarslan, and C. Ceylan (2003). Osteogenic ability of free perichondreal autografts in canine tibial defects: an experimental study. Journal of Experimental Animal Science 42(4): 203-217. ISSN: 0939-8600.
NAL Call Number: QL1.J687
Abstract: This study set out to establish the effect of transplanting perichondreum on bone healing at sites of tibial bone defects in an experimental dog model. Transplantation of free, autologous, non-vascularised, perichondreal grafts to the distal of right anteromedial plane side of the tibia was compared with non-transplantation on the proximal side of the same bone. In experimental dogs (n=7), a 5 cm piece segment of perichondreum, that has been excised from the thirteenth rib of the same animal, was transplanted to the midddle defect fracture site of bone, but not to the control proximal defect fracture site. The dogs were allowed to recover from the operation and were kept 21 days in cages, with free-range. On days 30 (Group I) and 45 (Group II) after operations, the dogs were euthanatized. Histopathologically, defects in 30 days treated perichondreum group were filled by new ossified tissue while control defects in the same period were not fully resurfaced. The new ossified tissue consisted of a thin and inadequate trabeculae. In 45 days treated groups, defects with transplanting perichondreum were filled by thick trabeculae converting into a compact bone tissue. The control defects of this group, however, were filled by an extreme callus overflowing to medulla and bone surface. This study has provided evidence to show that autologous, non-vascularized perichondreum retains an osteogenic ability when transplanted to tibial bone defect sites. It appears that callus formation occurred within the perichondreum grafting which resembles that of enchondral and intramembranous ossification.
Descriptors: methods and techniques, skeletal system, movement and support, tibial bone defects, bone disease, perichondrial autograft, experimental surgical techniques, laboratory techniques, ossification .

Beebe, K.S., J. Benevenia, B.E. Tuy, C.A. DePaula, R.D. Harten, and W.F. Enneking (2009). Effects of a new allograft processing procedure on graft healing in a canine model: a preliminary study. Clinical Orthopaedics and Related Research 467(1): 273-80.
Abstract: Graft healing in vivo can be affected by allograft processing. We asked whether a new processing technique influenced graft-host healing compared with autograft and a standard processing technique in a canine ulna model. We used bilateral intercalary allografts or autografts in the ulna of 13 skeletally mature male coonhounds. Each animal received two allografts, either one autograft and one allograft, or two autografts. At term (90 days), the graft sites were harvested. We assessed union with high-resolution xray imaging. Each specimen was processed for nondecalcified histologic analysis to assess the graft-host interface. Quantitative histomorphometric analysis was performed to determine spatial location and area of bone. Radiographic analysis, histologic analysis, and histomorphometric measures revealed no differences in union, mean total bone area, or total endosteal/intramedullary bone for the new process, standard process, and autografts. Our preliminary data suggest the new processing techniques may increase the safety of allograft transplantation without adversely affecting union when compared with standard processing techniques and autograft in a canine model.
Descriptors: bone transplantation, fracture healing, tissue and organ harvesting methods, ulna fractures surgery, dogs, models, animal, pilot projects, transplantation, autologous, transplantation, homologous, ulna fractures pathology, ulna fractures radiography.

Brandt, K.D., G.N.J. Smith, and S.L. Myers (2004). Hyaluronan injection affects neither osteoarthritis progression nor loading of the oa knee in dogs. Biorheology 41(3-4): 493-502. ISSN: 0006-355X.
NAL Call Number: QH505.A1B5
Abstract: We previously reported that intraarticular injections of hyaluronan (HA), administered prophylactically to dogs in whom knee osteoarthritis had been induced by transection of the anterior cruicate ligament, did not significantly modify the intraarticular pathology but decreased the proteogylcan concentration of the articular cartilage by as much as 30%. Because the cartilage proteoglycan concentration is directly related to the stiffness of the tissue, these results raised the possibility that intraarticular HA therapy could exacerbate OA. In the present study, using a different HA formulation, with a longer interval between intraarticular HA injection and examination of joint tissues, we found that neither prophylactic nor therapeutic administration of HA had an effect on the severity of OA pathology, the magnitude of vertical ground reaction forces generated by the unstable hind limb (a surrogate for joint pain), or the cartilage proteoglycan concentration. The data suggest that the suppression of proteoglycan synthesis induced by HA is temporary and fully reversible and that HA injections do not result in overloading of the OA extremity. A significant correlation was noted between the severity of chondropathy and the magnitude of the vertical ground reaction forces generated by the unstable limb.
Descriptors: animal care, pharmacology, skeletal system, movement and support, osteoarthritis, joint disease.

Candido, P.L. and B.J. Konig (2004). Histological analysis of bone/heteroplastic implant interfaces in dog tibia. Annals of Anatomy 186(1): 69-73. ISSN: 0940-9602.
Abstract: This work presents histological analysis of interfaces between bone and heteroplastic implants in dog tibias. The study was performed in four tibias (of four mongrel dogs) into which cylindrical implants were inserted. One ceramic (titania) implant and three grit-blasted titanium implants (with sandblasted and acid-corroded surfaces) were chosen for histological analysis of the implant surface/bone tissue interface. The implants remained in the tibias for eight months and none were loaded during this period. The animals were subsequently sacrificed and the samples were processed for analysis. Light microscope analysis revealed a large amount of osteoid tissue and proximity of osteoblasts and osteocytes to the implant surfaces. In addition, little or no fibrous tissue was observed between the bone and implant surfaces. The titanium implants presented better osseointegration than did the ceramic implant.
Descriptors: biomedical engineering, allied medical sciences, methods and techniques, orthopedics, human medicine, medical sciences, biotitatnium implant, prosthetic, bone, heteroplastic implant, prosthetic, ceramic titania implant, prosthetic, grit blasted titanium implant, prosthetic, histological analysis, histology and cytology techniques, laboratory techniques, light microscope analysis, imaging and microscopy techniques, subperiosteal implant, prosthetic .

Cerri, D.G., L.C. Rodrigues, S.R. Stowell, D.D. Araujo, M.C. Coelho, S.R. Oliveira, J.C. Bizario, R.D. Cummings, M. Dias Baruffi, and M.C. Costa (2008). Degeneration of dystrophic or injured skeletal muscles induces high expression of Galectin-1. Glycobiology 18(11): 842-50.
NAL Call Number: QP901.J6
Abstract: Muscle degenerative diseases such as Duchenne Muscular Dystrophy are incurable and treatment options are still restrained. Understanding the mechanisms and factors responsible for muscle degeneration and regeneration will facilitate the development of novel therapeutics. Several recent studies have demonstrated that Galectin-1 (Gal-1), a carbohydrate-binding protein, induces myoblast differentiation and fusion in vitro, suggesting a potential role for this mammalian lectin in muscle regenerative processes in vivo. However, the expression and localization of Gal-1 in vivo during muscle injury and repair are unclear. We report the expression and localization of Gal-1 during degenerative-regenerative processes in vivo using two models of muscular dystrophy and muscle injury. Gal-1 expression increased significantly during muscle degeneration in the murine mdx and in the canine Golden Retriever Muscular Dystrophy animal models. Compulsory exercise of mdx mouse, which intensifies degeneration, also resulted in sustained Gal-1 levels. Furthermore, muscle injury of wild-type C57BL/6 mice, induced by BaCl(2) treatment, also resulted in a marked increase in Gal-1 levels. Increased Gal-1 levels appeared to localize both inside and outside the muscle fibers with significant extracellular Gal-1 colocalized with infiltrating CD45(+) leukocytes. By contrast, regenerating muscle tissue showed a marked decrease in Gal-1 to baseline levels. These results demonstrate significant regulation of Gal-1 expression in vivo and suggest a potential role for Gal-1 in muscle homeostasis and repair.
Descriptors: galectin 1 metabolism, muscle, skeletal injuries, muscle, skeletal metabolism, muscular dystrophy, animal metabolism, antigens, cd45 immunology, antigens, cd45 metabolism, dogs, fluorescent antibody technique, galectin 1 analysis, leukocytes metabolism, mice, mice, inbred c57bl, mice, inbred mdx, models, animal, muscular dystrophy, animal chemically induced, regeneration physiology.

Coleman, J.C., R.T. Hart, and D.B. Burr (2003). Reconstructed bone end loads on the canine forelimb during gait. Journal of Biomechanics 36(12): 1837-1844. ISSN: 0021-9290.
NAL Call Number: TA166.J6
Abstract: The objective of this work was to determine bone loading conditions that, when applied to a finite element model, would best reproduce the in vivo strain field as measured by surface-mounted strain rosettes. The present study adopts the basic mathematical approach to load reconstruction introduced by Weinans and Blankevoort (J. Biomech. 28 (1995) 739) who determined the relationship between applied loads and bone strain distribution using ex vivo calibration testing. Our method eliminates the need for subsequent ex vivo calibration tests by instead substituting a computational calibration procedure. This first application of the method is with in vivo strains on the canine forelimb during gait (Coleman et al., J. Biomech. 35 (2002) 1677), but with further refinements the method could be used to reconstruct the in vivo loading conditions in living subjects.
Descriptors: methods and techniques, models and simulations, computational biology, skeletal system, movement and support, finite element model, gait .

Cui, L., B. Liu, G. Liu, W. Zhang, L. Cen, J. Sun, S. Yin, W. Liu, and Y. Cao (2007). Repair of cranial bone defects with adipose derived stem cells and coral scaffold in a canine model. Biomaterials 28(36): 5477-86. ISSN: 0142-9612.
NAL Call Number: R857.M3B48
Abstract: Adipose derived stem cells (ASCs) with osteogenic differentiation potential have been documented as an alternative cell source for bone regeneration. However, most of previous in vivo studies were carried out on small animals along with relatively short-term follow-up. In this study, we investigated the feasibility of using ASCs and coral scaffolds to repair a cranial bone defect in a canine model, and followed up the outcome for up to 6 month. Autologous ASCs isolated from canine subcutaneous fat were expanded, osteogenically induced, and seeded on coral scaffolds. Bilateral full-thickness defects (20 mm x 20 mm) of parietal bone were created. The defects were either repaired with ASC-coral constructs (experimental group) or with coral alone (control group). Three-dimensional CT scan showed that new bones were formed in the experimental group at 12 weeks post-implantation, while coral scaffolds were partially degraded in the control group. By radiographic analysis at 24 weeks post-transplantation, it was shown that an average of 84.19+/-6.45% of each defect volume had been repaired in experimental side, while the control side had only 25.04+/-18.82% of its volume filled. Histological examination revealed that the defect was repaired by typical bone tissue in experimental side, while only minimal bone formation with fibrous connection was observed in the control group. The successful repair of critical-sized bone defects via the current approach substantiates the potentiality of using ASCs with coral scaffolds for bone regeneration.
Descriptors: adipocytes cytology, craniofacial abnormalities pathology, craniofacial abnormalities surgery, skull abnormalities, skull cytology, stem cell transplantation methods, stem cells cytology, cell differentiation, cell separation, craniofacial abnormalities ultrastructure, dogs, microscopy, electron, scanning, models, animal, tomography, x ray computed.

d'Anjou, M.A., E. Troncy, M. Moreau, F. Abram, J.P. Raynauld, J. Martel Pelletier, and J.P. Pelletier (2008). Temporal assessment of bone marrow lesions on magnetic resonance imaging in a canine model of knee osteoarthritis: impact of sequence selection. Osteoarthritis and Cartilage OARS, Osteoarthritis Research Society 16(11): 1307-11.
NAL Call Number: RC931.O67
Abstract: OBJECTIVE: To assess the evolution of bone marrow lesions (BMLs) in a canine model of knee osteoarthritis (OA) using three different magnetic resonance imaging (MRI) sequences. DESIGN: Three MRI sequences [coronal, T1-weighted three-dimensional fast gradient recalled echo (T1-GRE), sagittal fat-suppressed 3D spoiled gradient echo at a steady state (SPGR), and sagittal T2-weighted fast spin echo with fat saturation (T2-FS)] were performed at baseline, and at week 4, 8 and 26 in five dogs following transection of the anterior cruciate ligament. The same reader scored (0-3) subchondral BMLs twice, in blinded conditions, according to their extent in nine joint subregions, for all imaging sessions, and independently on the three MRI sequences. Correlation coefficients and Bland-Altman plots evaluated intra-reader repeatability. Readings scores were averaged and the nine subregions were summed to generate global BML scores. RESULTS: BMLs were most prevalent in the central and medial portions of the tibial plateau. Intra-reader repeatability was good to excellent for each sequence (r(s)=0.87-0.97; P<0.001). Maximal intra-reader variability (24%) was reached on T2-FS and was associated to higher scores (P<0.05). Global BML scores increased similarly on all three sequences until week 8 (P<0.05). At week 26, score on T2-FS was decreased, being lower when compared to T1-GRE and SPGR (P<0.05). CONCLUSION: In this canine OA model, the extent of BMLs varies in time on different MRI sequences. Until the complex nature of these lesions is fully resolved, it is suggested that to accurately assess the size and extent of BMLs, a combination of different sequences should be used.
Descriptors: bone marrow pathology, bone marrow diseases pathology, knee joint pathology, magnetic resonance imaging methods, osteoarthritis, knee pathology, dogs, models, animal.

Decramer M , Reid M B , and De Troyer A (1985). Relationship between parasternal intercostal length and rib cage displacement in dogs. Journal of Applied Physiology 58(5): 1517-1520. ISSN: 8750-7587.
NAL Call Number: 447.8 J825
Abstract: The relationship between parasternal intercostal length and rib cage cross-sectional area was examined in 9 supine dogs during passive inflation and during quiet breathing before and after phrenicotomy. Parasternal intercostal length (PSL) was measured with a sonomicrometry technique and rib cage cross-sectional area (Arc) was measured with a Respitrace coil placed around the middle rib cage. During active inspiration as well as during passive inflation, PSL decreased as Arc increased. However, the relationship between PSL and Arc during active inspiration, whether in the intact or phrenicotomized animal, was almost invariably different from that during passive inflation, so that the same increase in Arc was associated with a greater decrease in PSL in the former than in the latter instance. This difference between passive inflation and active inspiration was probably due to the active contraction of the parasternals during inspiration and the consequent caudal displacement of the sternum. In upright humans, the sternum moved cephalad and not caudad during inspiration, so the relationship between PSL and Arc during active breathing might be similar to that during passive inflation.
Descriptors: muscular system, movement and support, nervous system, neural coordination, respiratory system, respiration, surgery, medical sciences, respiratory muscle passive inflation active inspiration.

Derwin, K.A., M.J. Codsi, R.A. Milks, A.R. Baker, J.A. McCarron, and J.P. Iannotti (2009). Rotator Cuff Repair Augmentation in a Canine Model with Use of a Woven Poly-L-Lactide Device. The Journal of Bone and Joint Surgery 91: 1159-1171. ISSN: 1535-1386.
Abstract: Despite advances in surgical treatment options, failure rates of rotator cuff repair have continued to range from 20% to 90%. Hence, there is a need for new repair strategies that provide effective mechanical reinforcement of rotator cuff repair as well as stimulate and enhance the intrinsic healing potential of the patient. The purpose of this study was to evaluate the extent to which augmentation of acute repair of rotator cuff tendons with a newly designed poly-L-lactide repair device would improve functional and biomechanical outcomes in a canine model. METHODS: Eight adult, male mongrel dogs (25 to 30 kg) underwent bilateral shoulder surgery. One shoulder underwent tendon release and repair only, and the other was subjected to release and repair followed by augmentation with the repair device. At twelve weeks, tendon retraction, cross-sectional area, stiffness, and ultimate load of the repair site were measured. Augmented repairs underwent histologic assessment of biocompatibility. In addition, eight pairs of canine cadaver shoulders underwent infraspinatus injury and repair with and without device augmentation with use of identical surgical procedures and served as time-zero biomechanical controls. Eight unpaired, canine cadaver shoulders were included as normal biomechanical controls. RESULTS: At time zero, repair augmentation significantly increased the ultimate load (23%) (p = 0.034) but not the stiffness of the canine infraspinatus tendon repair. At twelve weeks, the poly-L-lactide scaffold was observed to be histologically biocompatible, and augmented repairs demonstrated significantly less tendon retraction (p = 0.008) and significantly greater cross-sectional area (137%), stiffness (26%), and ultimate load (35%) than did repairs that had not been augmented (p < 0.001, p = 0.002, and p = 0.009, respectively). CONCLUSIONS: While limiting but not eliminating tendon repair retraction, the augmentation device provided a tendon-bone bridge and scaffold for host tissue deposition and ingrowth, resulting in improved biomechanical function of the repair at twelve weeks.
Descriptors: male mongrel dogs, bilateral shoulder surgery, canine cadaver shoulders, tendon release, tendon retraction, stiffness, poly-L-lactide scaffold, repair

Di Pasquale, D.J., M. Bhandari, A. Tov, and E.H. Schemitsch (2007). The effect of high and low pressure pulsatile lavage on soft tissue and cortical blood flow: a canine segmental humerus fracture model. Archives of Orthopaedic and Trauma Surgery 127(10): 879-84. ISSN: 0936-8051.
NAL Call Number: RD731
Abstract: OBJECTIVE: To determine the effect of high pressure pulsatile lavage (HPPL) and low pressure pulsatile lavage (LPPL) on cortical and soft tissue blood flow in a canine humerus segmental fracture model. DESIGN: Midshaft humeral osteotomies to create a 2-cm segment of diaphyseal bone were performed on bilateral canine humeri. Each osteotomy site was irrigated using either high pressure (n = 6) or low pressure (n = 5) pulsatile lavage prior to stabilization with a 5-mm steinman pin. Perfusion of cortical bone, periosteum, and biceps muscle was measured using Laser Doppler Flowmetry during four intraoperative intervals: pre-osteotomy, post-osteotomy, post-lavage, and post-nailing. RESULTS: Following osteotomy, a significant drop occurred in cortical perfusion (HPPL P = 0.049, LPPL P = 0.021) and in periosteal flow (HPPL P = 0.019, LPPL P = 0.012). Following irrigation there was no significant decrease in blood flow in either group for muscle (HPPL P = 0.249, LPPL P = 0.41), periosteum (HPPL P = 0.381, LPPL P = 0.402), or cortex (HPPL P = 0.398, LPPL P = 0.352) measurements. There was no significant difference between irrigation groups in post-lavage perfusion values for muscle (P = 0.326), periosteum (P = 0.452), and cortex (P = 0.464). Cortical perfusion decreased significantly post-nailing (HPPL P = 0.027, LPPL P = 0.047). Measurements did not differ significantly between groups at any other time interval. CONCLUSION: Although previous work has demonstrated an association between HPPL and detrimental structural changes in bone, this study demonstrates that HPPL does not adversely affect cortical or soft tissue blood flow acutely. Further, LPPL offers no acute benefit to cortical or soft tissue perfusion.
Descriptors: humeral fractures surgery, humerus blood supply, irrigation methods, muscle, skeletal blood supply, periosteum blood supply, dogs, fracture fixation, intramedullary, humerus surgery, laser doppler flowmetry, models, animal, osteotomy, pressure, regional blood flow.

Dubowitz, V. (2004). Current and future therapy in muscular dystrophy; need for a common language between basic scientists and clinicians. Acta Myologica 23(2): V-IX. ISSN: 1128-2460.
Abstract: This paper reviews the current therapy of Duchenne dystrophy, with the only two effective means of prolonging ambulation being the provision of knee-ankle-foot orthoses, and administration of corticosteroids, and the prospects, for the future application in Duchenne dystrophy, of ongoing research in cell therapy, gene therapy, protein upregulation and pharmacological possibilities. A critical review is also provided on the inappropriate nomenclature currently used and the need for a common language between basic and clinical scientists. Amongst the major problems are equating the mdx mouse, with its mild clinical phenotype, and Duchenne dystrophy, with its clearly defined severe clinical phenotype; the use of inappropriate and often emotive terminology to describe the pathological changes, such as "rescue", "reversal", "prevention", in place of describing the actual changes in acceptable descriptive language; and the use of the term therapy, in place of experiments, both in the basic laboratory studies and also the clinical experiments of injection of cells or gene constructs into single small muscles. A missing link in the multidisciplinary efforts, in this field, is the almost total absence of mouse doctors, who can define, at a clinical level, the motor, respiratory and cardiac deficits in the dystrophic animal, and bridge the gap between the mouse scientists doing experimental studies in the laboratory and the clinicians and veterinarians involved in the care of humans and dogs with these disorders and speaking the same language in relation to the clinical aspects and the pathology.
Descriptors: Duchenne dystrophy, corticosteroid administration, cell therapy, gene therapy, experimental studies, clinical practice, human.

Eisenschenk, A., C. Witzel, M. Lautenbach, A. Ekkernkamp, U. Weber, and M.V. Kuntscher (2007). Does chemotherapy impair the bone healing and biomechanical stability of vascularized rib and fibula grafts? Journal of Reconstructive Microsurgery 23(1): 35-40. ISSN: 0743-684X.
Abstract: The purpose of this study was to observe the impact of chemotherapy on the healing and biomechanical properties of vascularized bone grafts. Ten male beagle dogs were divided into two experimental groups: a chemotherapy group (CH) and control group (C). Group CH received adjuvant and neo-adjuvant chemotherapy. Each animal of both groups underwent the following operative procedures. The 5th and 7th rib were removed and replaced by vascularized pedicle transfers of the adjacent 4th and 8th rib. Additionally, a free fibular flap was elevated and retransferred to the same anatomic position. The rate of bony union on plain x-ray was 100 percent in group C, 30 percent in the vascularized rib, and 80 percent in the fibula grafts of group CH. Microangiography demonstrated no avascular bone segments in group C and in the fibula flaps of group CH. The vascularized ribs of group CH presented with 20 percent avascular bone segments. Biomechanical tests focusing on the durability of the vascularized grafts against bending and torsion forces demonstrated a reduction of the average maximum bending times by 17 percent and 23.9 percent compared to the controls ( P < 0.05). The twisting times were reduced by 13.8 percent (n.s.) and 32.5 percent ( P < 0.05). The data demonstrated a clear worsening in bone healing and stability after simulated adjuvant and neo-adjuvant chemotherapy. Thus, a large animal model was established for the further determination of the effects of chemotherapy on different vascularized bone transfers.
Descriptors: antineoplastic agents pharmacology, bone transplantation pathology, bone and bones drug effects, angiography, antibiotics, antineoplastic pharmacology, antimetabolites, antineoplastic pharmacology, biomechanics, chemotherapy, adjuvant, dogs, doxorubicin pharmacology, fibula, methotrexate pharmacology, microradiography, models, animal, neoadjuvant therapy, pliability, ribs, torque, wound healing drug effects.

Eswaran, S.K., M.R. Allen, D.B. Burr, and T.M. Keaveny (2007). A computational assessment of the independent contribution of changes in canine trabecular bone volume fraction and microarchitecture to increased bone strength with suppression of bone turnover. Journal of Biomechanics 40(15): 3424-31. ISSN: 0021-9290.
NAL Call Number: TA166.J6
Abstract: This study addressed the effects of changes in trabecular microarchitecture induced by suppressed bone turnover-including changes to the remodeling space-on the trabecular bone strength-volume fraction characteristics independent of changes in tissue material properties. Twenty female beagle dogs, aged 1-2 years, were treated daily with either oral saline (n=10 control) or high doses of oral risedronate (0.5mg/kg/day, n=10 suppressed) for a period of 1 year, the latter designed (and confirmed) to substantially suppress bone turnover. High-resolution micro-CT-based finite element models (18-mum voxel size) of canine trabecular bone cores (n=2 per vertebral body) extracted from the T-10 vertebrae were analyzed in both compressive and torsional loading cases. The same tissue-level material properties were used in all models, thus providing measures of tissue-normalized strength due only to changes in the microarchitecture. Suppressed bone turnover resulted in more plate-like architecture with a thicker and more dense trabecular structure, but the relationship between the microarchitectural parameters and volume fraction was unaltered (p>0.05). Though the suppressed group had a greater tissue-normalized strength as compared to the control group (p<0.001) for both compressive and torsional loading, the relationship between tissue-normalized strength and volume fraction was not significantly altered for compression (p>0.13) or torsion (p>0.09). In this high-density, non-osteoporotic animal model, the increases in tissue-normalized strength seen with suppression of bone turnover were entirely commensurate with increases in bone volume fraction and thus, no evidence of microarchitecture-related or "stress-riser" effects which may disproportionately affect strength were found.
Descriptors: bone density physiology, bone and bones cytology, bone and bones metabolism, computer simulation, dogs, finite element analysis, models, animal, stress, mechanical, tomography, x ray computed.

Flores Gasca, E., L. Rodriguez Fragoso, G.G. Farina, and J.R. Esparza (2003). Evaluation of the healing and integration of demineralized bone using an allograft in plate in osteotomies in dogs. FASEB Journal 17(4-5): A565. ISSN: 0892-6638.
NAL Call Number: QH301.F3
Descriptors: skeletal system, animal model, segmental bone defect, tibia, osteotomy, angiogenesis, osteoblast activity, laboratory techniques, therapeutic and prophylactic techniques

Frost Christensen, L.N., S.C. Mastbergen, M.E. Vianen, A. Hartog, J. DeGroot, G. Voorhout, A.M. van Wees, F.P. Lafeber, and H.A. Hazewinkel (2008). Degeneration, inflammation, regeneration, and pain/disability in dogs following destabilization or articular cartilage grooving of the stifle joint. Osteoarthritis and Cartilage OARS, Osteoarthritis Research Society 16(11): 1327-35.
Abstract: OBJECTIVE: The most used model for joint instability is the canine anterior cruciate ligament transection (ACLT)-model. The ACLT-model can be extended with a medial meniscectomy (MX) (i.e., ACLT-MX-model) to avoid unintentional, and with that variable, meniscal damage. The present study compares the ACLT-MX-model with the more recently introduced Groove-model on longitudinal measurements of osteophyte formation and gait as a surrogate marker of pain and disability, in addition to structural endpoint parameters. METHODS: Degenerative joint damage was induced Labrador dogs according to the ACLT-MX-model (n=7) or Groove-model (n=7). Every 4 weeks radiographs were taken to analyze osteophyte formation. Every 2 weeks gait was recorded using force-plate analysis. Joints were analyzed for features of degeneration 12 weeks after surgery. RESULTS: Both models showed similar osteophyte formation and gait changes for both experimental and contra-lateral control joints, although more pronounced for the ACLT-MX-model. This was supported by the structural endpoint measurements. Cartilage integrity, chondrocyte activity and synovial inflammation revealed similar characteristics of degenerative joint disease in both groups, again more pronounced in the ACLT-MX-model. CONCLUSIONS: The ACLT-MX-model demonstrates characteristics of joint degeneration that are related to moderate to severe osteoarthritis with clear synovial inflammatory activity. The Groove-model is a less painful and a significantly milder model of joint degeneration. The latter model might be more suitable to study subtle changes as a result of intervention than the more robust ACLT-MX-model.
Descriptors: anterior cruciate ligament injuries, cartilage, articular physiology, joint instability physiopathology, osteoarthritis physiopathology, regeneration physiology, stifle physiology, anterior cruciate ligament pathology, arthralgia etiology, arthralgia physiopathology, cartilage, articular injuries, cartilage, articular pathology, chondrocytes pathology, dogs, gait physiology, inflammation, joint instability pathology, models, animal, osteophyte pathology.

Fujii, Y. (2003). Treatment of diaphragmatic fatigue with inhaled aminophylline therapy in an experimental canine model: an open-label, dose-ranging, pharmacologic study. Current Therapeutic Research 64(9): 725-732. ISSN: 0011-393X.
Abstract: Background: Diaphragmatic fatigue may contribute to the development of respiratory failure. Although aminophylline administered IV has been widely used to treat diaphragmatic fatigue, to date it has not been used in aerosol formulation for this purpose. Objective: The aim of this study was to assess the efficacy of inhaled aminophylline on contractility of fatigued diaphragm in an experimental canine model. Methods: This open-label, dose-ranging, pharmacologic study was conducted at the Department of Anesthesiology, University of Tsukuba Institute of Clinical Medicine, Tsukuba (Ibaraki, Japan). Diaphragmatic fatigue was induced in healthy, male, mongrel dogs by intermittent supramaximal bilateral electrophrenic stimulation at a low frequency (20 Hz) applied for 30 minutes. Immediately after the end of the fatigue-producing period, group 1 received inhaled vehicle only, group 2 received inhaled aminophylline 12.5 mg/mL, group 3 received inhaled aminophylline 25 mg/mL, and group 4 was infused with verapamil 0.1 mg/kgcntdotmin during inhalation of aminophylline 25 mg/mL. Diaphragmatic contractility was assessed using transdiaphragmatic pressure (Pdi). Results: Twenty-eight dogs were used in the study (7 dogs were assigned to each treatment group). When fatigue was established, Pdi at low-frequency stimulation decreased significantly from baseline in all groups (all P < 0.05), and no significant change in Pdi was found at high-frequency stimulation. In groups 2 and 3, during aminophylline inhalation, Pdi at 20-Hz stimulation increased significantly from fatigued values (both P < 0.05). Pdi increased significantly more in group 3 than in group 2 (P < 0.05). In group 4, infusion of verapamil offset the increase in Pdi seen with aerosolized aminophylline in fatigued diaphragm. The integrated electrical activity of the diaphragm did not change significantly in any group. Conclusions: Inhaled aminophylline significantly improved contractility of fatigued diaphragm in a dose-related manner in this experimental canine model (P < 0.05). Its potent effect ay be caused by transmembrane calcium movement.
Descriptors: nervous system, neural coordination, pharmacology, diaphragmatic fatigue, muscle disease, drug therapy, dose ranging pharmacologic study, open label.

Fukuroku, J., N. Inoue, B. Rafiee, F.H. Sim, F.J. Frassica, and E.Y. Chao (2007). Extracortical bone-bridging fixation with use of cortical allograft and recombinant human osteogenic protein-1. Journal of Bone and Joint Surgery. American Volume 89(7): 1486-96. ISSN: 0021-9355.
Abstract: BACKGROUND: Prosthetic reconstruction with extracortical bone-bridging fixation is an effective method for the treatment of massive bone loss. We evaluated the effect of the use of recombinant human osteogenic protein-1 (rhOP-1) combined with allogenic cortical bone strips as a substitute for an autogenous bone graft for extracortical bone-bridging. METHODS: Eight skeletally mature adult male dogs underwent a bilateral resection of a 6-cm segment of the femoral diaphysis and reconstruction with a porous segmental prosthesis. On the experimental side, an allogenic cortical onlay graft in the form of bone strips combined with rhOP-1 mixed with bovine type-I-collagen putty (OP-1 putty) was applied. On the control side, allogenic cortical bone strips augmented with autogenous cancellous bone chips and bone marrow were used. The reconstructions were followed for twelve weeks with biweekly evaluations of load-bearing gait and radiographs. The animals were killed twelve weeks after the surgery, and the reconstructed femora were studied biomechanically, histologically, and with microradiographs. RESULTS: One animal was excluded from the analysis because a fracture of the proximal part of the femur on the control side was observed radiographically twelve weeks after the surgery. There were no significant differences in load-bearing gait between the experimental and control sides throughout the experimental period. Serial radiographs revealed a 1.9-fold (p<0.04), 2.7-fold (p<0.01), and 2.4-fold (p<0.03) increase in mineralized area on the experimental side at two, four, and six weeks, respectively. The torsional stiffness and strength of the fixation attributed to the extracortical bridging bone alone were 2.3-fold (p<0.03) and 2.2-fold (p=0.058) greater on the experimental side, respectively. The allograft porosity on the experimental side was 3.8-fold (p<0.02) greater than that on the control side. With the number of samples available, there was no significant difference in mineral apposition rate between the experimental and control sides. CONCLUSIONS: In an animal model of segmental bone-replacement prosthetic fixation with use of the extracortical bone-bridging principle, an allogenic onlay cortical graft combined with rhOP-1 was an effective substitute for autogenous bone graft.
Descriptors: bone morphogenetic proteins pharmacology, bone transplantation, femur surgery, prostheses and implants, transforming growth factor beta pharmacology, biomechanics, bone morphogenetic protein 7, dogs, femur radiography, models, animal, osseointegration, prosthesis design, transplantation, homologous, weight bearing.

Gilbert, T.W., A. Nieponice, A.R. Spievack, J. Holcomb, S. Gilbert, and S.F. Badylak (2008). Repair of the thoracic wall with an extracellular matrix scaffold in a canine model. Journal of Surgical Research 147(1): 61-7. ISSN: 0022-4804.
Abstract: Naturally derived extracellular matrix (ECM) scaffolds have been successfully used to promote constructive remodeling of injured or missing tissue in a variety of anatomical locations, including abdominal wall repair. Furthermore, ECM scaffolds have shown the ability to resist infection and adhesion formation. The present study investigated the utility of an ECM scaffold, specifically, porcine urinary bladder matrix (UBM), for repair of a 5 x 5 cm full-thickness lateral thoracic wall defect in a canine model (n = 6) including 5-cm segments of the 6th and 7th rib. The resected portion of the 7th rib was replaced as an interpositional graft along with the UBM scaffold. As a control, a Gore-Tex patch was used to repair the same defect (n = 2). The control animals healed by encapsulation of the Gore-Tex patch by dense collagenous tissue. The remodeled UBM grafts showed the presence of site-specific tissue, including organized fibrous connective tissue, muscle tissue, adipose tissue, and bone. Upon fluoroscopic examination, it was shown that both bony defects were replaced with new calcified bone. In the 6th rib space, new bone bridged the entire span. In the 7th rib space, there was evidence of bone formation between the interpositional graft and the existing bone, as well as de novo formation of organized bone in the shape of the missing rib segment parallel to the interpositional graft. This study shows that a naturally occurring ECM scaffold promotes site-specific constructive remodeling in a large thoracic wall defect.
Descriptors: extracellular matrix transplantation, surgical mesh, thoracic wall surgery, bone regeneration, dogs, fluoroscopy, models, animal, swine, urinary bladder.

Gilbert, T.W., A.M. Stewart Akers, A. Simmons Byrd, and S.F. Badylak (2007). Degradation and remodeling of small intestinal submucosa in canine Achilles tendon repair. Journal of Bone and Joint Surgery. American Volume 89(3): 621-30. ISSN: 0021-9355.
Abstract: BACKGROUND: Extracellular matrix derived from porcine small intestinal submucosa is used for the repair of musculotendinous tissues. Preclinical evaluation and clinical use have suggested that small intestinal submucosa extracellular matrix degrades rapidly after implantation and can be replaced by host tissue that is functionally and histologically similar to the normal tissue. METHODS: The present study analyzed the temporal degradation of a ten-layer multilaminate device of small intestinal submucosa extracellular matrix used for the repair of canine Achilles tendon and examined the corresponding histological appearance of the remodeled tissue during the course of scaffold degradation. Devices were fabricated from small intestinal submucosa extracellular matrix labeled with 14C. The amount of 14C remaining in the remodeled graft was measured by liquid scintillation counting at three, seven, fourteen, twenty-eight, sixty, and ninety days after surgery. Blood, urine, feces, and other parenchymal tissues were also harvested to determine the fate of scaffold degradation products. Tissue specimens were prepared for routine histological analysis to examine the morphology of the remodeled graft at each time-point. RESULTS: The small intestinal submucosa extracellular matrix graft degraded rapidly, with approximately 60% of the mass lost by one month after surgery, and the graft was completely resorbed by three months after surgery. The graft supported rapid cellular infiltration and host tissue ingrowth. By ninety days after surgery, the remodeled small intestinal submucosa extracellular matrix consisted of a dense collagenous tissue with organization, cellularity, and vascularity similar to that of normal tendon. CONCLUSIONS: Small intestinal submucosa extracellular matrix is rapidly degraded after implantation for the repair of a musculotendinous tissue in this canine Achilles tendon repair model and is replaced by the deposition and organization of host tissue that is histologically similar to that of normal tissue.
Descriptors: achilles tendon physiology, extracellular matrix transplantation, intestinal mucosa transplantation, achilles tendon cytology, achilles tendon injuries, carbon radioisotopes, dogs, extracellular matrix physiology, intestinal mucosa cytology, intestine, small cytology, models, animal, swine, transplantation, heterologous.

Gill, A.B. (2008). Transplantation of entire bones with their joint surface: A. Bruce Gill MD (1876-1965). The 6th president of the AAOS 1937. Clinical Orthopaedics and Related Research 466(1): 47-9. ISSN: 0009-921X.
Descriptors: bone transplantation history, joints surgery, bone transplantation methods, dogs, history, 19th century, history, 20th century, models, animal, orthopedics history.

Green, S.L., J.M. Westendorf, H. Jaffe, H.C. Pant, L.C. Cork, E.A. Ostrander, F. Vignaux, and J.E.J. Ferrell (2005). Allelic variants of the canine heavy neurofilament (NFH) subunit and extensive phosphorylation in dogs with motor neuron disease. Journal of Comparative Pathology 132(1): 33-50. ISSN: 0021-9975.
NAL Call Number: 41.8 J82
Abstract: Aberrant accumulation of extensively phosphorylated heavy (high molecular weight) neurofilament (NFH) and neurodegeneration are features of hereditary canine spinal muscular atrophy (HCSMA), an animal model of human motor neuron disease. In this study, the canine NFH gene was mapped, cloned, and sequenced, and electrospray/mass spectrometry was used to evaluate the phosphorylation state of NFH protein from normal dogs and dogs with HCSMA. The canine NFH gene was localized to a region on canine chromosome 26 that corresponds to human NFH on chromosome 22q. The predicted length of the canine NFH protein is 1135 amino acids, and it shares an 80.3% identity with human NFH and >74.6% with murine NFH proteins. Direct sequencing of NFH cDNA from HCSMA dogs revealed no mutations, although cDNA sequence and restriction fragment length polymorphism (RFLP) analysis indicates that there are at least three canine NFH alleles, differing in the position and number (61 or 62) of Lys-Ser-Proline (KSP) motifs. The two longest alleles (L1 and L2), each with 62 KSP repeats, contain an additional 24-base insert and were observed in both normal and HCSMA dogs. However, the shorter allele (the C allele), with 61 KSP sites and lacking the 24-base insertion, was absent in dogs with HCSMA. Mass spectrometry data indicated that almost all of the NFH KSP phosphorylation sites were occupied. No new or extra sites were identified in native NFH purified from the HCSMA dogs. The predominance of the two longest NFH alleles and the additional KSP phosphorylation sites they confer probably account for the presence of extensively phosphorylated NFs detected immunohistochemically in dogs with HCSMA.
Descriptors: animal model, human motor neuron disease, genetics, hereditary canine spinal muscular atrophy (HCSMA), neurodegeneration .
Notes: Library: National-Library-of-Medicine.

Green, S.L., D.M. Bouley, M.J. Pinter, L.C. Cork, and G.T. Vatassery (2001). Canine motor neuron disease: clinicopathologic features and selected indicators of oxidative stress. Journal of Veterinary Internal Medicine 15(2): 112-119. ISSN: 0891-6640.
NAL Call Number: SF601.J65
Abstract: Hereditary canine spinal muscular atrophy (HCSMA) is an inherited motor neuron disease affecting a kindred of Brittanies. We have examined the clinicopathologic abnormalities in 57 animals with HCSMA, including 43 affected adult dogs and 14 homozygote pups. We also measured selected biochemical indices of oxidative stress: serum vitamin E (alpha-tocopherol) and Se concentrations; serum concentrations of Cu, Zn, Mg, and Fe; and total superoxide dismutase and glutathione peroxidase activities in red blood cells. Dogs with HCSMA had the following abnormalities: regenerative anemia, hypoglobulinemia, hypochloremia, and abnormally high creatine kinase and liver alkaline phosphatase activities. Serum Cu concentration was significantly (P = .01) increased in adult dogs with HCSMA compared to control dogs. Serum vitamin E concentrations tended to be lower in adult dogs with HCSMA compared to controls, and were significantly (P = .01) lower in homozygote pups compared to control pups.
Descriptors: veterinary medicine, medical sciences, neural coordination, hereditary canine spinal muscular atrophy, nervous system disease, motor neuron disease, muscle disease, clinicopathologic features, oxidative stress.

Hannafin, J.A., S.P. Arnoczky, A. Hoonjan, and P.A. Torzilli (1995). Effect of stress deprivation and cyclic tensile loading on the material and morphologic properties of canine flexor digitorum profundus tendon: an in vitro study. Journal of Orthopaedic Research 13(6): 907-914. ISSN: 0736-0266.
Abstract: The effect of stress deprivation and cyclic tensile loading on the mechanical and histologic properties of the canine flexor digitorum profundus tendon was examined using an in vitro system. Stress deprivation resulted in a progressive and statistically significant decrease in the tensile modulus over an 8-week period. Histologically, stress-deprived tendons demonstrated quantitative changes in the morphology and number of cells and in the alignment of collagen. The change in tensile properties was not associated with an alteration in the water content of the tissue, but the change appeared to be dependent on the presence of a viable cell population. Dead (acellular) tendons did not undergo any alteration in tensile modulus in this in vitro system. In vitro cyclic tensile loading of tendons over a 4-week time period resulted in a significant increase in the tensile modulus (93% of the control) compared with that of the stress-deprived tendons (68% of the control). This loading regimen also maintained the normal histologic pattern of the tendons. The results of this study are similar to those previously reported for in vivo studies and suggest that this in vitro model may represent a valid system with which to test the effects of various stress conditions on the tensile properties of tissues.
Descriptors: biochemistry and molecular biophysics, cell biology, muscular system, movement and support, skeletal system, movement and support, collagen, immobilization, orthopedics, photomicrograph, viable cell population.

Hoshino, M., T. Egi, H. Terai, T. Namikawa, and K. Takaoka (2007). Regenerative repair of long intercalated rib defects using porous cylinders of beta-tricalcium phosphate: an experimental study in a canine model. Plastic and Reconstructive Surgery 119(5): 1431-9.
Abstract: BACKGROUND: In maxillofacial, spinal, and orthopedic surgery, bony ribs have been used as a source of donor bone. The resultant defects are not usually repaired, despite the pain or cosmetic morbidity experienced by the patient. The authors evaluated the efficacy of an osteoconductive beta-tricalcium phosphate and the contribution of the periosteum in rib bone regeneration. METHODS: Two 8-cm-long intercalated rib defects were generated in each of 30 beagle dogs. In the first group (n = 15), one defect was implanted with 16 small, short, porous beta-tricalcium phosphate cylinders that were connected with a titanium wire, and the other defect was left untreated. In the remaining 15 dogs, the periosteum was devitalized by ethanol, and then the same surgical procedures were performed. Each group was subdivided into three groups (n = 5), and the animals were euthanized at 3, 6, and 12 weeks. Bone regeneration was assessed radiologically, histologically, and mechanically. RESULTS: In the defect implanted with beta-tricalcium phosphate on intact periosteum, newly formed bone was present on and in the beta-tricalcium phosphate cylinders and bridged both ends of the resected ribs at 12 weeks, with replacement of beta-tricalcium phosphate by new bone. Mechanical testing of these ribs revealed that they had 70 percent of the strength of normal ribs when compared in a bending stress test at 12 weeks after surgery. No regenerative bone bridging the rib defects was seen in the ethanol-devitalized or untreated groups. CONCLUSIONS: Porous beta-tricalcium phosphate cylinders placed in tandem on the intact periosteum might be useful for the repair of rib bone donated at surgery, presenting a new and unique method for regenerating rib defects.
Descriptors: biocompatible materials, bone regeneration, calcium phosphates, prostheses and implants, ribs surgery, dogs, materials testing, models, animal, porosity, prosthesis design.

Jakobsen, T., J. Baas, J.E. Bechtold, B. Elmengaard, and K. Soballe (2007). Soaking morselized allograft in bisphosphonate can impair implant fixation. Clinical Orthopaedics and Related Research 463: 195-201. ISSN: 0009-921X.
Abstract: The use of impacted, morselized allograft is a well-established way to provide initial stability of revision joint replacements. We investigated whether rinsing morselized allograft in bisphosphonate and subsequently impacting it around experimental titanium-coated implants would further facilitate biomechanical implant fixation and graft incorporation. In 10 dogs, a pair of titanium implants surrounded by a 2.5-mm gap was inserted into the proximal part of each humerus during two separate surgeries to allow two observation periods. The gap was filled with impacted, morselized allograft soaked in either bisphosphonate (alendronate, 2 mg/mL) or saline (control). Unbound alendronate was not rinsed away. During the first surgery, one pair of implants (alendronate and control) was inserted into one humerus. Eight weeks later, a second pair of implants was inserted into the contralateral humerus. The first pair of implants was observed for 12 weeks and the second pair for 4 weeks. Implants were evaluated by histomorphometry and biomechanical pushout test. We found substantially decreased biomechanical implant fixation for all implants surrounded by impacted, morselized allograft that had been soaked in alendronate. Furthermore, the alendronate treatment blocked formation of new bone and inhibited resorption of the graft material. Although limited by the specific dose of alendronate used and the omission of rinsing away excess bisphosphonate, this study warrants caution and calls for further experimental research before impacting alendronate-soaked morselized allograft around clinical joint replacements.
Descriptors: alendronate adverse effects, arthroplasty, replacement methods, bone density conservation agents adverse effects, bone transplantation, osseointegration drug effects, prostheses and implants, prosthesis failure, arthroplasty, replacement instrumentation, biomechanics, dogs, humerus drug effects, humerus pathology, humerus surgery, models, animal, prosthesis design, titanium, transplantation, homologous.

Jakobsen, T., J. Baas, S. Kold, J.E. Bechtold, B. Elmengaard, and K. Soballe (2009). Local bisphosphonate treatment increases fixation of hydroxyapatite-coated implants inserted with bone compaction. Journal of Orthopaedic Research Official Publication of the Orthopaedic Research Society 27(2): 189-94.
Abstract: It has been shown that fixation of primary cementless joint replacement can independently be enhanced by either: (1) use of hydroxyapatite (HA) coated implants, (2) compaction of the peri-implant bone, or (3) local application of bisphosphonate. We investigated whether the combined effect of HA coating and bone compaction can be further enhanced with the use of local bisphosphonate treatment. HA-coated implants were bilaterally inserted into the proximal tibiae of 10 dogs. On one side local bisphosphonate was applied prior to bone compaction. Saline was used as control on the contralateral side. Implants were evaluated with histomorphometry and biomechanical push-out test. We found that bisphosphonate increased the peri-implant bone volume fraction (1.3-fold), maximum shear strength (2.1-fold), and maximum shear stiffness (2.7-fold). No significant difference was found in bone-to-implant contact or total energy absorption. This study indicates that local alendronate treatment can further improve the fixation of porous-coated implants that have also undergone HA-surface coating and peri-implant bone compaction.
Descriptors: alendronate pharmacology, bone density conservation agents pharmacology, coated materials, biocompatible, durapatite, osseointegration drug effects, prostheses and implants, dogs, materials testing, models, animal, shear strength drug effects, tibia drug effects, tibia surgery, titanium.

Jensen, T.B., O. Rahbek, S. Overgaard, and K. Soballe (2004). Platelet rich plasma and fresh frozen bone allograft as enhancement of implant fixation - an experimental study in dogs. Journal of Orthopaedic Research 22(3): 653-658. ISSN: 0736-0266.
Descriptors: blood and lymphatics, transport and circulation, skeletal system, movement and support, surgery, medical sciences, bone grafting, clinical techniques, therapeutic and prophylactic techniques, implant fixation, clinical techniques, titanium alloy implant, prosthetic, bone formation, enhancement, gap healing, enhancement .

Kwack, K.S., J.H. Cho, M.S. Kim M, C.S. Yoon, Y.S. Yoon, J.W. Choi, J.W. Kwon, B.H. Min, J.S. Sun, and S.Y. Kim (2008). Comparison study of intraarticular and intravenous gadolinium-enhanced magnetic resonance imaging of cartilage in a canine model. Acta Radiologica Stockholm, Sweden 1987 49(1): 65-74.
Abstract: BACKGROUND: Magnetic resonance (MR) imaging and measurement of glycosaminoglycan (GAG) have potential for characterization of hyaline articular cartilage. Recently, some reports have demonstrated the potential of direct administration of contrast media for MR imaging of cartilage. PURPOSE: To prove the feasibility of intraarticular gadolinium-enhanced MR imaging of cartilage (iGEMRIC) and T1 relaxation mapping of the articular cartilage in vivo with intraarticular injection of Gd-DTPA2-. MATERIAL AND METHODS: Five healthy beagle dogs underwent MR imaging and T1 relaxation mapping of the knee joints of both hind legs. The delayed gadolinium-enhanced MR imaging of cartilage (dGEMRIC) and iGEMRIC techniques were interchanged with MR imaging. For dGEMRIC, a double routine dose of Gd-DTPA2- (0.2 mM/kg) was administered intravenously. For iGEMRIC, 2.5 and 1.25 mmol/l saline-diluted Gd-DTPA2- solutions were separately injected into the right and left knee joints, respectively, prior to MR imaging. Color-coded T1 maps of 20 femoral condyles were obtained from the dGEMRIC and iGEMRIC images. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and glycosaminoglycan (GAG) delineation of articular cartilage were compared between the dGEMRIC and iGEMRIC techniques. RESULTS: The mean SNR was higher with dGEMRIC than with iGEMRIC, but the difference was not statistically significant (P=0.174). The mean (+/-SD) CNR was higher with iGEMRIC (-11.6+/-3.4) than with dGEMRIC (-16.7+/-4.0; P=0.000), although the absolute value of the CNR was higher with dGEMRIC. The layering and gradient distribution of GAG were more clearly visualized on the iGEMRIC images. The mean scores of GAG delineation with dGEMRIC and iGEMRIC were 0.7+/-0.6 and 2.2+/-1.7, respectively. The iGEMRIC method better visualized GAG distribution (P=0.001). CONCLUSION: Although the SNR did not differ significantly between the iGEMRIC and dGEMRIC techniques, the color-coded T1 map produced with iGEMRIC allowed better cartilage evaluation. Thus, iGEMRIC exhibits the useful features of both MR arthrography and dGEMRIC, and provides a color-coded T1 map that is useful for diagnosing early articular cartilage damage.
Descriptors: cartilage, articular anatomy and histology, contrast media administration and dosage, gadolinium dtpa administration and dosage, hindlimb anatomy and histology, image enhancement methods, magnetic resonance imaging methods, dogs, dose response relationship, drug, feasibility studies, glycosaminoglycans analysis, image processing, computer assisted, injections, intra articular, injections, intravenous, models, animal, sensitivity and specificity.

Lahm, A., P.C. Kreuz, A. El Tayeh, E. Mrosek, M. Oberst, J. Haberstroh, and H. Merk (2007). Loss of zonal organization of articular cartilage after experimental subchondral trauma of the knee joint. Saudi Medical Journal 28(4): 649-52. ISSN: 0379-5284.
Descriptors: bone and bones injuries, cartilage, articular injuries, cartilage, articular pathology, knee joint pathology, dogs, imaging, three dimensional, magnetic resonance imaging, models, animal, osteoarthritis, knee pathology.

Lahm, A., M. Uhl, M. Edlich, C. Erggelet, J. Haberstroh, and P.C. Kreuz (2005). An experimental canine model for subchondral lesions of the knee joint. The Knee 12(1): 51-5. ISSN: 0968-0160.
Abstract: Aim of the study was to create an animal model for the investigation of the role of subchondral bone damage without initial cartilage lesion in the pathogenesis of osteoarthritis, the mechanical properties of the joints as well as its role in cartilage metabolism. Therefore, after cadaver studies an animal model was created to apply a transarticular load to the femoro-patellar joint under reproducible conditions and produce a pure subchondral damage without affecting the articular cartilage. Following the cadaver studies a first group of four dogs was impacted to identify forces to produce isolated subchondral fractures in the femoral condyle. Then a second group of 12 dogs knee joints was impacted under identical conditions with forces of approximately 2100 N to produce similar subchondral fractures without cartilage damage in one joint under MRI control: T1-weighted SE-sequences. T2-weighted TSE, fat suppressed TIRM-sequences and 3D-FLASH fat saturated sequences. FLASH 3D-sequences revealed intact cartilage after impact in all cases and TIRM-sequences showed subchondral fractures representing bleeding, microfractures and fragmented bone trabecules. Turbo spin echo sequences and T1-weighted images revealed other intact intraarticular structures such as ligaments and menisci. The proposed experimental animal model is suitable to investigate the effect of pure subchondral damage on the articular cartilage and on means of treatment of cartilage defects without surgical intervention and without initial cartilage damage.
Descriptors: animal model. subchondral lesions, subchondral bone damage, cartilage lesion, pathogenesis, osteoarthritis.
Notes: Library: National-Library-of-Medicine.

Lahm, A., M. Uhl, C. Erggelet, J. Haberstroh, and E. Mrosek (2004). Articular cartilage degeneration after acute subchondral bone damage: an experimental study in dogs with histopathological grading. Acta Orthopaedica Scandinavica 75(6): 762-7. ISSN: 0001-6470.
Abstract: BACKGROUND: Subchondral fracture patterns and bone bruises have been described and some clinical studies have shown alterations in the initially healthy cartilage after such lesions. METHODS AND RESULTS: After having performed cadaver studies, we created an animal model to produce pure subchondral damage without affecting the articular cartilage, under MRI control. We used 12 beagle dogs. For quantification of different degrees of staining, we used a grading of the sections by means of the HHGS (Histological-Histochemical Grading System) or Mankin score. RESULTS: In all cases, FLASH 3D sequences revealed intact cartilage in MRI after impact. The best detection of subchondral fractures was achieved in fat-suppressed TIRM sequences. Image analysis based on the HHGS showed changes in 10 of 12 samples, with a high degree of significance 6 months after the initial trauma. Correlation analysis showed loss of the physiological distribution of proteoglycans and glycoproteins in the different zones of articular cartilage. Subcategories "Structure", "Cells" and "Safranin-O Staining" also showed high significance, and the category "Tidemark Integrity" showed a tendency. INTERPRETATION: Our findings indicate that acute subchondral fractures are a predictor of degenerative changes within 6 months. Modifications and supplements to rehabilitation might be needed in cases with accompanying subchondral lesions, e.g. in ACL tears.
Descriptors: animal model, beagle dogs, subchondral damage, articular cartilage, rehabilitation.

Lahm, A., M. Uhl, H.A. Lehr, C. Ihling, P.C. Kreuz, and J. Haberstroh (2004). Photoshop-based image analysis of canine articular cartilage after subchondral damage. Archives of Orthopaedic and Trauma Surgery 124(7): 431-6. ISSN: 0936-8051.
Abstract: INTRODUCTION: The validity of histopathological grading is a major problem in the assessment of articular cartilage. Calculating the cumulative strength of signal intensity of different stains gives information regarding the amount of proteoglycan, glycoproteins, etc. Using this system, we examined the medium-term effect of subchondral lesions on initially healthy articular cartilage. MATERIALS AND METHODS: After cadaver studies, an animal model was created to produce pure subchondral damage without affecting the articular cartilage in 12 beagle dogs under MRI control. Quantification of the different stains was provided using a Photoshop-based image analysis (pixel analysis) with the histogram command 6 months after subchondral trauma. RESULTS: FLASH 3D sequences revealed intact cartilage after impact in all cases. The best detection of subchondral fractures was achieved with fat-suppressed TIRM sequences. Semiquantitative image analysis showed changes in proteoglycan and glycoprotein quantities in 9 of 12 samples that had not shown any evidence of damage during the initial examination. Correlation analysis showed a loss of the physiological distribution of proteoglycans and glycoproteins in the different zones of articular cartilage. CONCLUSION: Currently available software programs can be applied for comparative analysis of histologic stains of hyaline cartilage. After subchondral fractures, significant changes in the cartilage itself occur after 6 months.
Descriptors: beagle dogs, animal model, subchondral damage, proteoglycan, glycoproteins, histologic stains, hyaline cartilage.

Lee, C.R., A.J. Grodzinsky, H.P. Hsu, and M. Spector (2003). Effects of a cultured autologous chondrocyte-seeded type ii collagen scaffold on the healing of a chondral defect in a canine model. Journal of Orthopaedic Research 21(2): 272-281. ISSN: 0736-0266.
Abstract: Using a previously established canine model for repair of articular cartilage defects, this study evaluated the 15-week healing of chondral defects (i.e., to the tidemark) implanted with an autologous articular chondrocyte-seeded type II collagen scaffold that had been cultured in vitro for four weeks prior to implantation. The amount and composition of the reparative tissue were compared to results from our prior studies using the same animal model in which the following groups were analyzed: defects implanted with autologous chondrocyte-seeded collagen scaffolds that had been cultured in vitro for approximately 12 h prior to implantation, defects implanted with autologous chondrocytes alone, and untreated defects. Chondrocytes, isolated from articular cartilage harvested from the left knee joint of six adult canines, were expanded in number in monolayer for three weeks, seeded into porous type II collagen scaffolds, cultured for an additional four weeks in vitro and then implanted into chondral defects in the trochlear groove of the right knee joints. The percentages of specific tissue types filling the defects were evaluated histomorphometrically and certain mechanical properties of the repair tissue were determined. The reparative tissue filled 88+-6% (mean+-SEM; range 70-100%) of the cross-sectional area of the original defect, with hyaline cartilage accounting for 42+-10% (range 7-67%) of defect area. These values were greater than those reported previously for untreated defects and defects implanted with a type II collagen scaffold seeded with autologous chondrocytes within 12 h prior to implantation. Most striking, was the decreased amount of fibrous tissue filling the defects in the current study, 5+-5% (range 0-26%) as compared to previous treatments. Despite this improvement, indentation testing of the repair tissue formed in this study revealed that the compressive stiffness of the repair tissue was well below (20-fold lower stiffness) that of native articular cartilage.
Descriptors: animal model, bone disease, repair, articular cartilage defects, chondral defects, autologous chondrocyte seeded type ii collagen scaffold, prosthetic, implantat, clinical techniques, therapeutic and prophylactic techniques.

Libicher, M., M. Ivancic, V. Hoffmann, and W. Wenz (2005). Early changes in experimental osteoarthritis using the Pond-Nuki dog model: technical procedure and initial results of in vivo MR imaging. European Radiology 15(2): 390-4. ISSN: 0938-7994.
NAL Call Number: R895.A1
Abstract: The purpose of this study was to prove the feasibility of combining in vivo MR imaging with the Pond-Nuki animal model for the evaluation of osteoarthritis. In an experimental study, 24 beagle dogs underwent transection of the anterior cruciate ligament of the left leg (modified Pond-Nuki model). The dogs were randomly assigned into four groups and examined by MRI after 6, 12, 24 and 48 weeks. MR imaging of both knees was performed under general anesthesia with the contralateral joint serving as control. In group 1 (6 weeks postoperatively), the first sign detected on MRI was subchondral bone marrow edema in the posteromedial tibia. After 12 weeks, erosion of the posteromedial tibial cartilage could be observed, followed by meniscus degeneration and osteophytosis after 24 and 48 weeks. The contralateral knee joint showed transient joint effusion, but no significant signs of internal derangement (P<0.001). By combining in vivo MR imaging with the Pond-Nuki model, it is possible to detect early signs of osteoarthritis. The first sign was posteromedial subchondral bone marrow edema in the tibia followed by progressive cartilage degeneration and joint derangement. The in vivo model therefore seems to be suitable for longitudinal studies or monitoring the therapeutic effects of osteoarthritis.
Descriptors: animal model, beagle dogs, osteoarthritis, transection of the anterior cruciate ligament, in vivo model, progressive cartilage degeneration, joint derangement, therapeutic effects.
Notes: Library: National-Library-of-Medicine.

Lopez, M.J., D. Kunz, R.J. Vanderby, D. Heisey, J. Bogdanske, and M.D. Markel (2003). A comparison of joint stability between anterior cruciate intact and deficient knees: a new canine model of anterior cruciate ligament disruption. Journal of Orthopaedic Research 21(2): 224-230. ISSN: 0736-0266.
Abstract: Transection of the canine anterior cruciate ligament (ACL) is a well-established osteoarthritis (OA) model. This study evaluated a new method of canine ACL disruption as well as canine knee joint laxity and joint capsule (JC) contribution to joint stability at two time points (16 and 26 weeks) after ACL disruption (n=5/time interval). Ten crossbreed hounds were evaluated with force plate gait analysis and radiographs at intervals up to 34 weeks after monopolar radiofrequency energy (MRFE) treatment of one randomly selected ACL. Each contralateral ACL was sham treated. The MRFE treated ACLs ruptured approximately eight weeks (mean 52.5 days, SEM+-1.0, range 48-56 days) after treatment. Gait analysis and radiographic changes were consistent with established canine ACL transection models of OA. Anterior-posterior (AP) translation and medial-lateral (ML) rotation were measured in each knee at 30degree, 60degree, and 90degree of flexion with and then without JC with loads of 40 N in AP translation and 4 Nm in ML rotation. A statistically significant interaction in AP translation included JC by cruciate (P=0.02), and there was a trend for a cruciate by time (P=0.07) interaction. Significant interactions in ML rotational testing included the presence of joint capsule (P=0.0001) and angle by cruciate (P=0.0012). This study describes a model in which canine ACLs predictably rupture approximately eight weeks after arthroscopic surgery and details the contribution of JC to canine knee stability in both ACL intact and deficient knees. The model presented here avoids the introduction of potential surgical variables at the time of ACL rupture and may contribute to studies of OA pathogenesis and inhibition. This model may also be useful for insight into the pathologic changes that occur in the knee as the ACL undergoes degeneration prior to rupture.
Descriptors: methods and techniques, skeletal system, movement and support, anterior cruciate ligament degeneration, bone disease, anterior cruciate ligament rupture, knee joint laxity, joint disease, osteoarthritis, joint disease, etiology, arthroscopic surgery, clinical techniques, therapeutic and prophylactic techniques, force plate gait analysis, clinical techniques, monopolar radiofrequency energy treatment, radiography, diagnostic techniques, anterior posterior translation, medial lateral rotation.

Lopez, M.J. and M.D. Markel (2003). Anterior cruciate ligament rupture after thermal treatment in a canine model. American Journal of Sports Medicine 31(2): 164-167. ISSN: 0363-5465.
Abstract: Background: The use of radiofrequency energy to treat damaged anterior cruciate ligaments is gaining popularity. However, complete rupture of the ligament after treatment has been reported. Purpose: To evaluate the effect of thermal energy applied arthroscopically to normal, intact anterior cruciate ligaments in mature dogs. Study Design: Controlled laboratory study. Methods: Monopolar radiofrequency energy was applied to the normal anterior cruciate ligament of 1 knee in 18 dogs. The contralateral anterior cruciate ligament (also normal) was sham treated. Force-plate gait analysis was performed preoperatively and at 4, 8, 12, 16, 26, and 36 weeks after surgery. Anterior cruciate ligament rupture was detected by a sudden onset of nonweightbearing and a positive drawer sign. Results: All treated ligaments ruptured approximately 55 days after surgery (mean, 55 days; standard error, 1.6). Conclusions: Although monopolar radiofrequency energy may have some potential in the treatment of lax anterior cruciate ligaments, in the application described here the result was a highly predictable deterioration and rupture of all treated anterior cruciate ligaments. Clinical Relevance: On the basis of these findings, we strongly recommend that strict selection and application criteria be used when considering use of this modality on anterior cruciate ligaments that are stretched or partially disrupted, or both. Use of this modality should be followed by adherence to a highly conservative rehabilitation protocol.
Descriptors: methods and techniques, skeletal system, movement and support, anterior cruciate ligament rupture, connective tissue disease, radiofrequency energy treatment, clinical techniques, therapeutic and prophylactic techniques.

Marin, C., R. Granato, M. Suzuki, J.N. Gil, A. Piattelli, and P.G. Coelho (2008). Removal torque and histomorphometric evaluation of bioceramic grit-blasted/acid-etched and dual acid-etched implant surfaces: an experimental study in dogs. Journal of Periodontology 79(10): 1942-9. ISSN: 0022-3492.
Abstract: BACKGROUND: Surface modifications to dental implants have been used in an attempt to accelerate the osseointegration process. The objective of this study was to biomechanically/histomorphometrically evaluate a bioceramic grit-blasted and acid-etched surface (BGB/AA; test) versus a dual acid-etched implant surface (control) in a beagle dog model. METHODS: Control and BGB/AA implants were subjected to a series of physicochemical characterization tools, including scanning electron microscopy (SEM), atomic force microscopy (AFM), and auger photoelectron spectroscopy (APS). The animal model included the placement of 72 implants along the proximal tibiae of six beagle dogs, which remained in place for 2 or 4 weeks. After euthanization, half of the specimens were biomechanically tested (removal torque), and the other half was non-decalcified processed to slides of approximately 30 microm thickness for histomorphologic and histomorphometric (percentage of bone-to-implant contact [%BIC]) evaluation. Analysis of variance at the 95% confidence level and the Tukey post hoc test were used for multiple comparisons. RESULTS: SEM and AFM showed that surface microtextures were qualitatively and quantitatively different and that the BGB/AA surface presented higher submicrometer average roughness values (R(a)) and root mean square (RMS) values compared to control surfaces. Ca and P were detected at the BGB/AA surface by APS. Higher degrees of bone organization were observed along the perimeter of the BGB/AA surface compared to control, despite the non-significant differences in %BIC between the surfaces (P >0.25). Significantly higher removal torque was observed for the BGB/AA implants at both time periods (P <0.0001). CONCLUSION: According to the biomechanical and histomorphologic results, early biomechanical fixation was positively affected by the BGB/AA surface compared to the dual-acid etched surface.
Descriptors: acid etching, dental methods, biocompatible materials chemistry, ceramics chemistry, dental etching methods, dental implants, torque, biomechanics, bone remodeling physiology, calcium analysis, carbon analysis, dental prosthesis design, dogs, electron probe microanalysis, materials testing, microscopy, atomic force, microscopy, electron, scanning, models, animal, osseointegration physiology, oxygen analysis, phosphorus analysis, surface properties, tibia pathology, tibia surgery, titanium analysis.

Martel, J., A. Bueno, M.P. Dominguez, P. Llorens, J. Quiros, and C. Delgado (2008). Percutaneous radiofrequency ablation: relationship between different probe types and procedure time on length and extent of osteonecrosis in dog long bones. Skeletal Radiology 37(2): 147-52. ISSN: 0364-2348.
NAL Call Number: RC78.A1
Abstract: PURPOSE: We have been using radiofrequency ablation for the percutaneous treatment of osteoid osteoma since 2001. Frequently, lesions are located near the joint surface, involve the vertebral body or are close to major nerves. We seek to determine whether radiofrequency ablation (RFA) can be used safely in these cases. MATERIALS AND METHODS: A total of 65 lesions were induced in 4 dogs. Each dog underwent RFA on the diaphysis of long bones, as well as femoral and humeral heads. Four different sessions were carried out by using 1- and 2-cm probes with or without a cool-tip system and by varying the timing of the procedure. Plain film, CT, and MRI were obtained. All bone samples were examined histologically. RESULTS: The dogs' activity after the procedure was normal. No pathologic fractures occurred despite unrestricted activity of the animals. Cortical bone was always respected; therefore, articular cartilage has not been damaged. Radiological findings were characteristic. There were no significant differences in lesion size, probe type, and the duration of the procedure. The mean lesion diameter perpendicular to the electrode was 18.5 mm. CONCLUSIONS: Our study confirms the insulative effect of cortical bone. RFA can be safely performed close to the joint surface without damaging the cartilage.
Descriptors: catheter ablation adverse effects, catheter ablation instrumentation, joint diseases prevention and control, leg bones pathology, leg bones radiography, osteonecrosis etiology, catheter ablation methods, dogs, femur head pathology, femur head radiography, humerus pathology, humerus radiography, leg bones injuries, magnetic resonance imaging, models, animal, osteonecrosis prevention and control, severity of illness index, time factors, tomography, x ray computed.

Meisel, H.J., T. Ganey, and W. Hutton (2003). Disc chondrocyte transplantation in a canine model: a treatment for degenerated or damaged intervertebral disc. International Journal of Artificial Organs 26(9): 870. ISSN: 0391-3988.
Descriptors: cell biology, skeletal system, movement and support, intervertebral disc damage, bone disease, therapy, intervertebral disc degeneration, bone disease, therapy, disc chondrocyte transplantation, laboratory techniques, therapeutic and prophylactic techniques.

Murray, C., F. Markos, H.M. Snow, T. Corcoran, N. Parfrey, and G.D. Shorten (2003). Effects of fenoldopam on renal blood flow and its function in a canine model of rhabdomyolysis. European Journal of Anaesthesiology 20(9): 711-718. ISSN: 0265-0215.
Abstract: Background and objective: Our hypothesis was that fenoldopam, a selective DA1 agonist, would protect against rhabdomyolysis-induced renal injury. Methods: We studied the effects of intravenous fenoldopam (0. 1-1.0 mug kg-1 min-1) or saline on renal blood flow and function in 10 anaesthetized Labrador dogs in whom rhabdomyolysis and myoglobinuric acute renal failure had been induced by administration of glycerol 50% (10 mL kg-1) intramuscularly. Haemodynamic measurements including renal blood flow and derived parameters of renal function including creatinine clearance were recorded before and for the 30 min following glycerol injection, and during the 3 h following commencement of each infusion. Serum malondialdehyde concentrations were measured before and 15 min after glycerol intramuscularly, and 30 and 150 min after commencement of the infusion. Results: In the fenoldopam group, creatinine clearance was less than placebo at 1 and 2 h after commencing the infusion (12.7+-11.5 versus 31.3+-9.9 mL min-1, P=0.04; 8.5+-5.3 versus 20.1+-7.4 mL min-1, P=0.03). A 140-fold increase in serum malondialdehyde concentration occurred in one dog (fenoldopam group). Conclusion: Fenoldopam increased the severity of the renal injury in this canine model of myoglobinuric acute renal failure.
Descriptors: muscular system, movement and support, pharmacology, urinary system, chemical coordination and homeostasis, myoglobinuric acute renal failure, urologic disease, renal injury, injury, urologic disease, rhabdomyolysis, muscle disease, hemodynamics, renal blood flow, renal function.

Narmoneva, D.A., H.S. Cheung, J.Y. Wang, D.S. Howell, and L.A. Setton (2002). Altered swelling behavior of femoral cartilage following joint immobilization in a canine model. Journal of Orthopaedic Research 20(1): 83-91. ISSN: 0736-0266.
Abstract: Periods of reduced joint loading have been shown to induce changes in the biochemical composition, metabolism and mechanics of articular cartilage. In this study, changes in cartilage swelling behavior were studied following a 4-week period of joint immobilization, using a recently developed osmotic loading technique (J. Biomech. 32 (1999) 401-408). The magnitude and distribution of swelling strains were measured in cartilage-bone samples equilibrated in physiological and hypotonic saline, relative to a hypertonic reference NaCl solution. Physicochemical parameters (glycosaminoglycan fixed charge density and water volume fraction) were determined in site-matched cartilage samples. The experimental data for swelling strains, fixed charge density and water volume fraction were used with a triphasic mechano-chemical theory (J. Biomech. Eng. 113 (1991) 245-258) to determine the effect of joint immobilization on the tensile modulus of the cartilage solid matrix. Four weeks of immobilization resulted in a significant increase in the magnitude of swelling-induced strains, and a significant decrease in fixed charge density in cartilage, as compared with the contralateral controls. Joint immobilization also resulted in decreases in values for the modulus of cartilage, as compared with the contralateral controls. Our results suggest that 4 weeks of joint immobilization had a significant effect on cartilage mechanical function that may be linked to collagen changes in the cartilage extracellular matrix.
Descriptors: methods and techniques, skeletal system, movement and support, osteoarthritis, joint disease, therapy, joint immobilization, therapeutic method, osmotic loading technique, therapeutic method, cartilage swelling behavior, swelling strain, distribution, magnitude, tensile modulus, water volume fraction.

Nehrer, S., H.A. Breinan, A. Ramappa, G. Young, S. Shortkroff, L.K. Louie, C.B. Sledge, I.V. Yannas, and M. Spector (1997). Matrix collagen type and pore size influence behaviour of the seeded canine chondrocytes. Biomaterials 18(11): 769-776. ISSN: 0142-9612.
NAL Call Number: R857.M3B48
Abstract: This study directly compared the behaviour of chondrocytes in porous matrices comprising different collagen types and different pore diameters. There was a dramatic difference in the morphology of the cells in the type I and type II collagen matrices. The cells in the type II collagen matrix retained their chondrocytic morphology and synthesized glycosaminoglycans, while in the type I matrix the chondrocytes displayed a fibroblastic morphology with less biosynthetic activity than those in the type II. Small pore diameter affected morphology initially in the type I matrices and showed a higher increase of DNA content, but with time the cells lost the chondrocytic morphology. Our results demonstrate the marked influence of collagen type and pore characteristics on the phenotypic expression of seeded chondrocytes.
Descriptors: biochemistry and molecular biophysics, cell biology, genetics, metabolism, methods and techniques, skeletal system, movement and support, adult, behavior, biobusiness, biomaterials, cartilage defect treatment, cartilage repair, chondrocyte, chondrocytic morphology, collagen, collagen pore size, dna, glycosaminoglycans, matrix collagen type, medical research, mongrel, phenotypic expression, porous matrices, seeded canine chondrocytes, skeletal system, tissue engineering.

Ohyama, T., Y. Kubo, H. Iwata, and W. Taki (2002). Beta-tricalcium phosphate as a substitute for autograft in interbody fusion cages in the canine lumbar spine. Journal of Neurosurgery 97(3 Supplement): 350-354. ISSN: 0022-3085.
Abstract: Object: An interbody fusion cage has been introduced for cervical anterior interbody fusion. Autogenetic bone is packed into the cage to increase the rate of union between adjacent vertebral bodies. Thus, donor site-related complications can still occur. In this study a synthetic ceramic, beta-tricalcium phosphate (TCP), was examined as a substitute for autograft bone in a canine lumbar spine model. Methods: In 12 dogs L-1 to L-4 vertebrae were exposed via a posterolateral approach, and discectomy and placement of interbody fusion cages were performed at two intervertebral disc spaces. One cage was filled with autograft (Group A) and the other with TCP (Group B). The lumbar spine was excised at 16 weeks postsurgery, and biomechanical, microradiographic, and histological examinations were performed. Both the microradiographic and histological examinations revealed that fusion occurred in five (41.7%) of 12 operations performed in Group A and in six (50%) of 12 operations performed in Group B. The mean percentage of trabecular bone area in the cages was 54.6% in Group A and 53.8% in Group B. There were no significant intergroup differences in functional unit stiffness. Conclusions: Good histological and biomechanical results were obtained for TCP-filled interbody fusion cages. The results were comparable with those obtained using autograft-filled cages, suggesting that there is no need to harvest iliac bone or to use allo- or xenografts to increase the interlocking strength between the cage and vertebral bone to achieve anterior cervical interbody fusion.
Descriptors: biomaterials, equipment, apparatus, devices and instrumentation, skeletal system, movement and support, cervical anterior interbody fusion, therapeutic method, interbody fusion cages, medical equipment, autograft .

Pearce, A.I., R.G. Richards, S. Milz, E. Schneider, and S.G. Pearce (2007). Animal models for implant biomaterial research in bone: a review. European Cells and Materials 13: 1-10.
NAL Call Number: R857.M3 E97
Abstract: Development of an optimal interface between bone and orthopaedic and dental implants has taken place for many years. In order to determine whether a newly developed implant material conforms to the requirements of biocompatibility, mechanical stability and safety, it must undergo rigorous testing both in vitro and in vivo. Results from in vitro studies can be difficult to extrapolate to the in vivo situation. For this reason the use of animal models is often an essential step in the testing of orthopaedic and dental implants prior to clinical use in humans. This review discusses some of the more commonly available and frequently used animal models such as the dog, sheep, goat, pig and rabbit models for the evaluation of bone-implant interactions. Factors for consideration when choosing an animal model and implant design are discussed. Various bone specific features are discussed including the usage of the species, bone macrostructure and microstructure and bone composition and remodelling, with emphasis being placed on the similarity between the animal model and the human clinical situation. While the rabbit was the most commonly used of the species discussed in this review, it is clear that this species showed the least similarities to human bone. There were only minor differences in bone composition between the various species and humans. The pig demonstrated a good likeness with human bone however difficulties may be encountered in relation to their size and ease of handling. In this respect the dog and sheep/goat show more promise as animal models for the testing of bone implant materials. While no species fulfils all of the requirements of an ideal model, an understanding of the differences in bone architecture and remodelling between the species is likely to assist in the selection of a suitable species for a defined research question.
Descriptors: bone substitutes, implants, experimental, materials testing, models, animal, bone remodeling, bone and bones anatomy and histology, dogs, goats anatomy and histology, rabbits, sheep anatomy and histology, swine anatomy and histology.

Pinter, M.J., R.F. Waldeck, N. Wallace, and L.C. Cork (1995). Motor unit behavior in canine motor neuron disease. Journal of Neuroscience 15(5 PART 1): 3447-3457. ISSN: 0270-6474.
NAL Call Number: RC346
Abstract: Hereditary canine spinal muscular atrophy (HCSMA) is an autosomally dominant disease of motor neurons that shares many pathological features with human motor neuron disease. A particularly striking feature of the affected, accelerated phenotype (homozygous HCSMA) is that profound weakness develops before appreciable motor neuron cell death occurs (Cork et al., 1989a), implying that motor unit functional defects occur initially. The purpose of this study was to identify the site of these defects and characterize their nature. In most young homozygotes (2-3 months postnatal), motor neurons were encountered that could support orthodromic action potential propagation to the muscle but did not activate muscle fibers. The tetanic forces of innervated motor units in young homozygotes tended to be smaller than those in closely age-matched clinically normal animals. In older homozygotes ( apprxeq 4.5 months, postnatal), all motor neurons sampled were capable of activating muscle fibers, but many motor units displayed abnormal behavior including an inability to sustain force output during high frequency activation. Motor units exhibiting tetanic failure also showed proportionately greater twitch potentiation than nonfailing units of similar unpotentiated twitch amplitude. Tetanic failure and large potentiation tended to occur in motor units that possessed the slowest contraction speeds. These results indicate that motor neuron functional defects in HCSMA appear initially in the most distal parts of the motor axon and involve defective neurotransmission. The possible roles of distal nerve degeneration, motor terminal sprouting, and synaptic transmission in causing these deficits are considered.
Descriptors: genetics, muscular system, movement and support, nervous system, neural coordination, hereditary spinal muscle atrophy, motor terminal sprouting, nerve degeneration, synaptic transmission.

Por, Y.C., C.R. Barcelo, K.E. Salyer, D.G. Genecov, K. Troxel, E. Gendler, M.E. Elsalanty, and L.A. Opperman (2007). Bone generation in the reconstruction of a critical size calvarial defect in an experimental model. Annals of the Academy of Medicine, Singapore 36(11): 911-9. ISSN: 0304-4602.
Abstract: OBJECTIVE: This study was designed to investigate the optimal combination of known osteogenic biomaterials with shape conforming struts to achieve calvarial vault reconstruction, using a canine model. METHODS: Eighteen adolescent beagles were divided equally into 6 groups. A critical size defect of 6 x 2 cm traversed the sagittal suture. The biomaterials used for calvarial reconstruction were demineralised perforated bone matrix (DBM), recombinant human bone morphogenetic protein-2 (rhBMP2) and autogenous platelet-rich plasma (PRP). The struts used were cobalt chrome (metal) or resorbable plate. The groupings were as follows: 1) DBM + metal, 2) DBM + PRP + metal, 3) DBM + PRP + resorbable plate, 4) DBM + rhBMP2 + metal, 5) DBM + rhBMP2 + PRP + metal, and 6) DBM + rhBMP2 + resorbable plate. Animals were euthanised at 3 months post-surgery. There was no mortality or major complications. Analysis was performed macroscopically, histologically, and with computed tomography (CT). RESULTS: There was complete bony regeneration in the rhBMP2 groups only. Non-rhBMP2 groups had minimal bony ingrowth from the defect edges and on the dural surface, a finding confirmed by CT scan and histology. PRP did not enhance bone regeneration. Shape conformation was good with both metal and resorbable plate. CONCLUSION: rhBMP2 but not PRP accelerated calvarial regeneration in 3 months. The DBM in the rhBMP2 groups were substituted by new trabecular bone. Shape molding was good with both metal and resorbable plate.
Descriptors: bone regeneration physiology, models, animal, skull pathology, biocompatible materials, bone morphogenetic proteins pharmacology, dogs, postoperative care, recombinant proteins pharmacology, reconstructive surgical procedures, skull growth and development, skull surgery, transforming growth factor beta pharmacology.

Qi, C. and H. Changlin (2007). Levels of biomarkers correlate with magnetic resonance imaging progression of knee cartilage degeneration: a study on canine. Knee Surgery, Sports Traumatology, Arthroscopy Official Journal of the ESSKA 15(7): 869-78. ISSN: 0942-2056.
Abstract: To examine the association between levers of cartilage oligomeric matrix protein (COMP), matrix metalloproteinases-1 (MMP-1), matrix metalloproteinases-3 (MMP-3), tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in serum and synovial fluid, and MR imaging of cartilage degeneration in knee joint, and to understand the effects of movement training with different intensity on cartilage of knee joint. 20 adult canines were randomly divided into three groups (8 in the light training group; 8 in the intensive training group; 4 in the control group), and canines of the two training groups were trained daily at different intensity. The training lasted for 10 weeks in all. Magnetic resonance imaging (MRI) examinations were performed regularly (2, 4, 6, 8, 10 week) to investigate the changes of articular cartilage in the canine knee, while concentrations of COMP, MMP-1, MMP-3, TIMP-1 in serum and synovial fluid were measured by ELISA assays. We could find imaging changes of cartilage degeneration in both the training groups by MRI examination during training period, compared with the control group. However, there was no significant difference between these two training groups. Elevations of levels of COMP, MMP-1, MMP-3, TIMP-1, MMP-3/TIMP-1 were seen in serum and synovial fluid after training, and their levels had obvious association with knee MRI grades of cartilage lesion. Furthermore, there were statistically significant associations between biomarkers levels in serum and in synovial fluid. Long-time and high-intensity movement training induces cartilage degeneration in knee joint. Within the intensity extent applied in this study, knee cartilage degeneration caused by light training or intensive training has no difference in MR imaging, but has a comparatively obvious difference in biomarkers level. To detect articular cartilage degeneration in early stage and monitor pathological process, the associated application of several biomarkers has a very good practical value, and can be used as a helpful supplement to MRI.
Descriptors: cartilage, articular pathology, knee joint pathology, magnetic resonance imaging, physical conditioning, animal methods, biological markers metabolism, dogs, enzyme linked immunosorbent assay, extracellular matrix proteins metabolism, glycoproteins metabolism, knee joint metabolism, matrix metalloproteinase 1 metabolism, matrix metalloproteinase 3 metabolism, models, animal, random allocation, synovial fluid metabolism, tissue inhibitor of metalloproteinase 1 metabolism.

Rogachefsky, R.A., R.D. Altman, M.S. Markov, and H.S. Cheung (2004). Use of a permanent magnetic field to inhibit the development of canine osteoarthritis. Bioelectromagnetics 25(4): 260-270. ISSN: 0197-8462.
Abstract: This study was designed to determine the potential of a permanent magnetic field to inhibit the progression of osteoarthritis (OA) in a canine model. The magnetic field was created by 72 domino-sized ceramic magnets with surface field strength of 1100 G (0.11 T). The magnetic field strength at the surface of the mattress was 450-500 G (45-50 mT) and was equally distributed over the mattress surface. Eighteen animals had closed resection of their right stifle anterior cruciate ligament. Their kennel floors were covered in one of three ways: no floor mattress (OA) (N = 6); a floor mattress with domino-sized ceramic pieces placed between two layers of foam (sham control OA-MAT) (N = 6); or a floor mattress with domino-sized ceramic permanent magnets placed between two layers of foam (OA-MAT-MAG) (N = 6). Animals were kept in their cages except for 4 h of exercise each day. The left stifle of six animals served as the normal control. The stifle joints were examined at 12 weeks for synovial effusion, gross anatomic appearance, microscopic anatomic appearance (Mankin score), and metalloproteinase (MMP)-1 and -3. Macroscopically, the OA-MAT-MAG group appeared to have less synovitis, less synovial effusion, less disruption of the cartilage surface, and less cartilage ulceration than did the OA group or the control mattress group. The mean Mankin score for the OA-MAT-MAG group was less than that for the OA group (4.2 +/- 0.8 vs. 6.7 +/- 0.3; P < .05) and the control mattress group (4.2 +/- 0.8 vs. 5.2 +/- 0.8; P > .05), but greater than that for the normal left group (4.2 +/- 0.8 vs. 1.0 +/- 0.4; P < .05). These scores show a trend of improvement for OA-MAT-MAG group but the difference with the sham control OA-MAT group was not statistically significant. In immunohistochemical studies, the OA-MAT-MAG group cartilage was stained less heavily for MMP-1 and MMP-3 than were the OA group cartilage and the control mattress group cartilage, but did not differ significantly in MMP-1 and MMP-3 from the normal left group cartilage. The OA-MAT-MAG group did not differ from the normal left group in MMP-3 as determined by Western blot analysis. The study suggests that OA of the medial femoral condyle developed in a canine model exposed to a magnetic field may be inhibited beyond the benefit provided by mattress. Further studies are needed to delineate more precisely the effect of the magnetic field in reducing the severity of OA.
Descriptors: enzymology, biochemistry and molecular biophysics, methods and techniques, skeletal system, movement and support, osteoarthritis, joint disease, diagnosis, radiotherapy, therapy, western blot analysis, genetic techniques, laboratory techniques, permanent magnetic field exposure, applied and field techniques.

Schulmerich, M.V., J.H. Cole, K.A. Dooley, M.D. Morris, J.M. Kreider, S.A. Goldstein, S. Srinivasan, and B.W. Pogue (2008). Noninvasive Raman tomographic imaging of canine bone tissue. Journal of Biomedical Optics 13(2): 020506. ISSN: 1083-3668.
Abstract: Raman spectroscopic diffuse tomographic imaging has been demonstrated for the first time. It provides a noninvasive, label-free modality to image the chemical composition of human and animal tissue and other turbid media. This technique has been applied to image the composition of bone tissue within an intact section of a canine limb. Spatially distributed 785-nm laser excitation was employed to prevent thermal damage to the tissue. Diffuse emission tomography reconstruction was used, and the location that was recovered has been confirmed by micro-computed tomography (micro-CT) images.
Descriptors: image enhancement methods, image interpretation, computer assisted methods, spectrum analysis, raman methods, tibia anatomy and histology, tomography, optical methods, dogs, models, animal.

Shimatsu, Y., K. Katagiri, T. Furuta, M. Nakura, and et al. (2003). Canine x-linked muscular dystrophy in japan (cxmdj). Experimental Animals (Tokyo) 52(2): 93-97. ISSN: 1341-1357.
NAL Call Number: QL55. J55
Abstract: The purpose of this study was to develop a strain of canine X-linked muscular dystrophy (CXMD), a model of Duchenne muscular dystrophy, in Japan. A female beagle was artificially inseminated with frozen-thawed spermatozoa derived from an affected golden retriever. Subsequently, two carrier female dogs (G1 carriers) and four normal male littermates were produced. Thereafter, the two G1 carriers were mated with beagle sires. As a result, each bitch whelped three times, and out of 54 pups, 17 affected male descendants, and 11 carrier female descendants (G2 carriers) were detected. One G2 carrier was then mated with a beagle sire and 15 pups in two whelpings were produced, including five affected males and four carrier females (G3 carriers). A total of 10 female beagles were artificially inseminated to evaluate the fertility of the frozen-thawed spermatozoa from the two affected dogs. The whelping rates of the two affected dogs were 4/5 and the litter sizes were 5.0+-1.41 and 6.0+-0.82, respectively. These results indicate that a canine X-linked muscular dystrophy colony has been established in Japan. We called them CXMDJ.
Descriptors: genetics, muscular system, movement and support, veterinary medicine, medical sciences, Duchenne muscular dystrophy, muscle disease, nervous system disease, canine X linked muscular dystrophy, genetic disease, artificial insemination, laboratory techniques.

Skurla, C.P., G.E. Pluhar, D.J. Frankel, E.L. Egger, and S.P. James (2005). Assessing the dog as a model for human total hip replacement. Analysis of 38 canine cemented femoral components retrieved at post-mortem. The Journal of Bone and Joint Surgery. British Volume 87(1): 120-7. ISSN: 0301-620X.
Abstract: Post-mortem retrieval of canine, cemented femoral components was analysed to assess the performance of these implants in the dog as a model for human total hip replacement (THR). Mechanical testing and radiological analysis were performed to determine the stability of the implant and the quality of the cement. Thirty-eight implants from 29 dogs were retrieved after time intervals ranging from 0.67 to 11.67 years. The incidence of aseptic loosening was 63.2%, much higher than in human patients (6% in post-mortem studies). Failure of the femoral implants began with debonding at the cement-metal interface, similar to that in implants in man. The incidence of aseptic loosening was much lower in bilateral than in unilateral implants. Significant differences were observed for three different designs of implant. While the dog remains the animal model of choice for THR, results from this study provide insight into interspecies differences in the performance of implants. For example, the performance of THR in dogs should be compared with that in young rather than in elderly human patients.
Descriptors: animal model, post-mortem, age differences, total hip replacement, hip implants, cemented femoral components, aseptic loosening, performance analysis.

Sumner, D.R., T.M. Turner, R.M. Urban, T. Turek, H. Seeherman, and J.M. Wozney (2004). Locally delivered rhbmp-2 enhances bone ingrowth and gap healing in a canine model. Journal of Orthopaedic Research 22(1): 58-65. ISSN: 0736-0266.
Abstract: The purpose of the present study was to determine if recombinant human bone morphogenetic protein-2 (rhBMP-2) enhances bone ingrowth into porous-coated implants and gap healing around the implants. In the presence of a 3-mm gap between the implant and host bone, porous-coated implants were placed bilaterally for four weeks in the proximal humeri of skeletally mature, adult male dogs. In three treatment groups, the test implant was treated with HA/TCP and rhBMP-2 in buffer at a dose of 100 mug/implant (n=5), 400 mug/implant (n=6), or 800 mug/implant (n=5) and placed in the left humerus. In these same animals, an internal control implant was treated only with HA/TCP and buffer and placed in the right humerus. These groups were compared with a previously reported external control group of seven animals in which no growth factor was delivered (J. Orthop. Res. 19 (2001) 85). The BMP treated implants in the two lower dose groups had significantly more bone ingrowth than the external controls with the greatest effect in the 100 g/implant group (a 3.5-fold increase over the external control, p=0.008). All three dose groups had significantly more bone formation in the 3-mm gap surrounding the BMP treated implants than the external controls with the greatest effect in the 800 mug group (2.9-fold increase, p<0.001). Thus, application of rhBMP-2 to a porous-coated implant stimulated local bone ingrowth and gap healing. The enhancement of bone formation within the implant (bone ingrowth) was inversely related to dose.
Descriptors: pharmacology, skeletal system, movement and support, bone ingrowth, gap healing.

Tanaka, T., C. Zhao, Y.L. Sun, M.E. Zobitz, K.N. An, and P.C. Amadio (2007). The effect of carbodiimide-derivatized hyaluronic acid and gelatin surface modification on peroneus longus tendon graft in a short-term canine model in vivo. Journal of Hand Surgery 32(6): 876-81. ISSN: 0363-5023.
Abstract: PURPOSE: We have recently reported that application of carbodiimide-derivatized hyaluronic acid and gelatin (cd-HA gelatin) to a peroneus longus tendon graft increased tendon graft gliding ability and decreased work of flexion compared with untreated grafts in a canine model in vivo. In this study, we investigated the effect of this modification on adhesions, stiffness, strength of the distal attachment, and fibroblast count. METHODS: A total of 24 dogs were used for this study. The peroneus longus tendons of each hind leg were grafted into the 2nd and 5th digits of one forepaw in each dog. One peroneus longus tendon was treated with cd-HA gelatin prior to grafting, and the other one was immersed in 0.9% saline solution as a control. Animals were killed 1, 3, or 6 weeks postoperatively. RESULTS: The adhesion score of cd-HA gelatin-treated tendons was significantly less than that in the saline-treated tendons at all time points. There was no significant difference in the indentation stiffness between HA- and saline-treated grafts at any time point. For the ultimate force at the distal attachment, there was a significant difference among the time points, with a steady increase over time, but no significant difference between treated and control tendons at any time point. There was no significant difference in fibroblast count between treated and control tendons at any time point. CONCLUSIONS: Although gross adhesion formation was less, there was no significant difference in strength at the distal tendon-bone interface, cellularity, or tendon graft stiffness when comparing saline-treated and cd-HA gelatin-treated tendon grafts in vivo.
Descriptors: adjuvants, immunologic pharmacology, ethyldimethylaminopropyl carbodiimide pharmacology, gelatin pharmacology, hyaluronic acid pharmacology, tendons transplantation, cell count, dogs, fibroblasts metabolism, models, animal, tendon injuries surgery, tensile strength, tissue adhesions pathology, tissue adhesions prevention and control, tissue transplantation methods.

Taylor, B.A., G.O. Okubadejo, A.A. Patel, M.R. Talcott, T. Imamura, N. Hu, and B.W. Cunningham (2008). Evaluation of total disc arthroplasty: a canine model. American Journal of Orthopedics Belle Mead, N.J. 37(4): E64-70.
Abstract: The study reported here was designed to examine the biomechanical and histopathologic properties of total disc arthroplasty (TDA) using a canine model. Thirty-seven dogs were divided into 3 groups (intact spine, fusion, TDA) and sacrificed either at study commencement or at 3 months. Results showed progressive fusion from 0 to 3 months in the fusion group. The TDA group maintained motion throughout this period. No neurologic complications were noted in either group. These results establish the canine as a model for future studies of TDA.
Descriptors: arthroplasty, replacement methods, intervertebral disk surgery, models, animal, prostheses and implants, arthroplasty, biomechanics, dogs, intervertebral disk physiopathology, prosthesis design, range of motion, articular, spinal fusion.

Thomopoulos, S., H. Matsuzaki, M. Zaegel, R.H. Gelberman, and M.J. Silva (2007). Alendronate prevents bone loss and improves tendon-to-bone repair strength in a canine model. Journal of Orthopaedic Research Official Publication of the Orthopaedic Research Society 25(4): 473-9. ISSN: 0736-0266.
Abstract: Previously we showed a loss of bone and a concomitant decrease in mechanical properties in the first 21 days after flexor tendon insertion site injury and repair in a canine model. The goal of this short-term study was to suppress bone loss after insertion site repair using alendronate in an attempt to prevent the reduction in biomechanical properties. Flexor tendons of the second and fifth digits of the right forelimbs of canines were injured and repaired. Dogs received a daily oral dose of alendronate (2 mg/kg). One digit in each dog also received a local dose of alendronate in the bone tunnel at the time of surgery. The repair was evaluated for bone mineral density (BMD) and biomechanical properties and compared to data from a previous study in which no alendronate was used. Alendronate was effective in protecting the distal phalanx from resorption during tendon-to-bone healing (BMD was 94 and 104% of control for systemic alendronate and for systemic plus local alendronate, respectively). Alendronate treatment prevented much of the decrease in ultimate load that occurs in the first 21 days. Without treatment, ultimate load was 42% of control. With systemic alendronate treatment and systemic plus local alendronate treatment, ultimate load was 78 and 69% of control, respectively. Failure mode was significantly different when comparing alendronate treatment to repair alone. A lower incidence of suture pull through was found in alendronate treated dogs, suggesting less tendon degeneration. Ultimate load can be improved in association with preventing the bone loss that normally occurs during the early period following tendon-to-bone repair. These initial short-term data demonstrate the potential for a clinical treatment that could enhance tendon-to-bone healing.
Descriptors: alendronate pharmacology, bone density conservation agents pharmacology, bone resorption prevention and control, bone and bones physiology, tendons physiology, wound healing drug effects, biomechanics, bone density drug effects, bone density physiology, bone resorption physiopathology, bone and bones drug effects, dogs, dose response relationship, drug, metalloproteases metabolism, models, animal, tendon injuries physiopathology, tendons drug effects, wound healing physiology.

Thomopoulos, S., E. Zampiakis, R. Das, M.J. Silva, and R.H. Gelberman (2008). The effect of muscle loading on flexor tendon-to-bone healing in a canine model. Journal of Orthopaedic Research Official Publication of the Orthopaedic Research Society 26(12): 1611-7.
Abstract: Previous tendon and ligament studies have demonstrated a role for mechanical loading in tissue homeostasis and healing. In uninjured musculoskeletal tissues, increased loading leads to an increase in mechanical properties, whereas decreased loading leads to a decrease in mechanical properties. The role of loading on healing tissues is less clear. We studied tendon-to-bone healing in a canine flexor tendon-to-bone injury and repair model. To examine the effect of muscle loading on tendon-to-bone healing, repaired tendons were either cut proximally (unloaded group) to remove all load from the distal phalanx repair site or left intact proximally (loaded group). All paws were casted postoperatively and subjected to daily passive motion rehabilitation. Specimens were tested to determine functional properties, biomechanical properties, repair-site gapping, and bone mineral density. Loading across the repair site led to improved functional and biomechanical properties (e.g., stiffness for the loaded group was 8.2 +/- 3.9 versus 5.1 +/- 2.5 N/mm for the unloaded group). Loading did not affect bone mineral density or gapping. The formation of a gap between the healing tendon and bone correlated with failure properties. Using a clinically relevant model of flexor tendon injury and repair, we found that muscle loading was beneficial to healing. Complete removal of load by proximal transection resulted in tendon-to-bone repairs with less range of motion and lower biomechanical properties compared to repairs in which the muscle-tendon-bone unit was left intact.
Descriptors: bone and bones physiology, muscle, skeletal physiology, tendons physiology, wound healing physiology, biomechanics, bone density physiology, dogs, homeostasis physiology, models, animal, range of motion, articular physiology.

Turner, R.T., A. Maran, S. Lotinun, T. Hefferan, G.L. Evans, M. Zhang, and J.D. Sibonga (2001). Animal models for osteoporosis. Reviews in Endocrine and Metabolic Disorders 2(1): 117-27. ISSN: 1389-9155.
Abstract: Animal models will continue to be important tools in the quest to understand the contribution of specific genes to establishment of peak bone mass and optimal bone architecture, as well as the genetic basis for a predisposition toward accelerated bone loss in the presence of co-morbidity factors such as estrogen deficiency. Existing animal models will continue to be useful for modeling changes in bone metabolism and architecture induced by well-defined local and systemic factors. However, there is a critical unfulfilled need to develop and validate better animal models to allow fruitful investigation of the interaction of the multitude of factors which precipitate senile osteoporosis. Well characterized and validated animal models that can be recommended for investigation of the etiology, prevention and treatment of several forms of osteoporosis have been listed in Table 1. Also listed are models which are provisionally recommended. These latter models have potential but are inadequately characterized, deviate significantly from the human response, require careful choice of strain or age, or are not practical for most investigators to adopt. It cannot be stressed strongly enough that the enormous potential of laboratory animals as models for osteoporosis can only be realized if great care is taken in the choice of an appropriate species, age, experimental design, and measurements. Poor choices will results in misinterpretation of results which ultimately can bring harm to patients who suffer from osteoporosis by delaying advancement of knowledge.
Descriptors: animal models, species differences, age differences, genetics, bone mass, osteoporosis, prevention, treatment.

Turner, T.M., R.M. Urban, D.J. Hall, and G.B. Andersson (2007). Bone ingrowth through porous titanium granulate around a femoral stem: histological assessment in a six-month canine hemiarthroplasty model. Upsala Journal of Medical Sciences 112(2): 191-7. ISSN: 0300-9734.
Abstract: The procedure of using of porous titanium granules for cementless fixation of a hip replacement femoral stem was studied in a hemiarthroplasty model in 10 canines for 6 months. A vibrating instrument was used to facilitate both the delivery and distribution of the irregularly shaped porous titanium granules into the femoral canal as well as the subsequent insertion of a titanium alloy stem into the intramedullary bed of granules. Histological examination revealed lamellar bone formation through the mantle of porous titanium granules in continuity with the surrounding cortex resulting in the formation of an integrated mantle of bone and titanium granulate around the prosthesis.
Descriptors: femur growth and development, models, animal, titanium, arthroplasty, replacement, hip, dogs, femur anatomy and histology, femur radiography, microscopy, electron, scanning, prosthesis design.

Wilson, J.R., N.A. Duncan, W.R. Giles, and R.B. Clark (2004). A voltage-dependent k+ current contributes to membrane potential of acutely isolated canine articular chondrocytes. Journal of Physiology 557(1): 93-104. ISSN: 0022-3751.
NAL Call Number: 447.8 J82
Abstract: The electrophysiological properties of acutely isolated canine articular chondrocytes have been characterized using patch-clamp methods. The'steady-state' current-voltage relationship (I-V) of single chondrocytes over the range of potentials from -100 to + 40 mV was highly nonlinear, showing strong outward rectification positive to the zero-current potential. Currents activated at membrane potentials negative to -50 mV were time independent, and the I-V from -100 to -60 mV was linear, corresponding to an apparent input resistance of 9.3 +/- 1.4 GOMEGA (n = 23). The outwardly rectifying current was sensitive to the K+ channel blocking ion tetraethylammonium (TEA), which had a 50% blocking concentration of 0.66 mM (at +50 mV). The 'TEA-sensitive' component of the outwardly rectifying current had time- and membrane potential-dependent properties, activated near -45 mV and was half-activated at -25 mV. The reversal potential of the 'TEA-sensitive' current with external K+ concentration of 5 mm and internal concentration of 145 mm, was - 84 mV, indicating that the current was primarily carried by K+ ions. The resting membrane potential of isolated chondrocytes (-38.1 +/- 1.4 mv, n = 19) was depolarized by 14.8 +/- 0.9 mV by 25 mM TEA, which completely blocked the K+ current of these cells. These data suggest that this voltage-sensitive K+ channel has an important role in regulating the membrane potential of canine articular chondrocytes.
Descriptors: biochemistry and molecular biophysics, skeletal system, movement and support, membrane potential.

Yuasa, K., M. Yoshimura, N. Urasawa, S. Ohshima, J.M. Howell, A. Nakamura, T. Hijikata, Y. Miyagoe Suzuki, and S. Takeda (2007). Injection of a recombinant AAV serotype 2 into canine skeletal muscles evokes strong immune responses against transgene products. Gene Therapy 14(17): 1249-60. ISSN: 0969-7128.
Abstract: Using murine models, we have previously demonstrated that recombinant adeno-associated virus (rAAV)-mediated microdystrophin gene transfer is a promising approach to treatment of Duchenne muscular dystrophy (DMD). To examine further therapeutic effects and the safety issue of rAAV-mediated microdystrophin gene transfer using larger animal models, such as dystrophic dog models, we first investigated transduction efficiency of rAAV in wild-type canine muscle cells, and found that rAAV2 encoding beta-galactosidase effectively transduces canine primary myotubes in vitro. Subsequent rAAV2 transfer into skeletal muscles of normal dogs, however, resulted in low and transient expression of beta-galactosidase together with intense cellular infiltrations in vivo, where cellular and humoral immune responses were remarkably activated. In contrast, rAAV2 expressing no transgene elicited no cellular infiltrations. Co-administration of immunosuppressants, cyclosporine and mycophenolate mofetil could partially improve rAAV2 transduction. Collectively, these results suggest that immune responses against the transgene product caused cellular infiltration and eliminated transduced myofibers in dogs. Furthermore, in vitro interferon-gamma release assay showed that canine splenocytes respond to immunogens or mitogens more susceptibly than murine ones. Our results emphasize the importance to scrutinize the immune responses to AAV vectors in larger animal models before applying rAAV-mediated gene therapy to DMD patients.
Descriptors: dependovirus genetics, gene therapy adverse effects, genetic vectors adverse effects, muscle, skeletal immunology, muscular dystrophy, animal therapy, muscular dystrophy, duchenne therapy, base sequence, calmodulin genetics, cyclosporine administration and dosage, dogs, dystrophin genetics, dystrophin metabolism, gene therapy methods, genetic engineering, genetic vectors genetics, immunosuppressive agents administration and dosage, injections, intramuscular, interferon gamma immunology, lymphocyte activation, mice, mice, inbred c57bl, models, animal, molecular sequence data, muscle fibers, skeletal immunology, muscle fibers, skeletal virology, muscular dystrophy, animal immunology, muscular dystrophy, duchenne immunology, parvoviridae infections immunology, rna, messenger analysis, reverse transcriptase polymerase chain reaction, species specificity, t lymphocytes, cytotoxic immunology, transduction, genetic methods, transgenes, beta galactosidase genetics.

Zhao, C., Y.L. Sun, M.E. Zobitz, K.N. An, and P.C. Amadio (2007). Enhancing the strength of the tendon-suture interface using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride and cyanoacrylate. Journal of Hand Surgery 32(5): 606-11. ISSN: 0363-5023.
Abstract: PURPOSE: Preventing gap or rupture is important to achieving a successful outcome after tendon repair. Weak sutures break; strong sutures fail by pull-out at the tendon-suture interface. In this study, we investigated the use of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and cyanoacrylate to enhance the strength of the tendon-suture interface. METHODS: Twenty-four canine flexor digitorum profundus tendons were used to test EDC and cyanoacrylate reinforcement methods, with 12 tendons in each group. A single-loop suture technique was used to test the tendon-suture interface strength. RESULTS: The mean ultimate strengths of the EDC group and the cyanoacrylate group were significantly higher than those of their respective control groups. The stiffness of the group with cyanoacrylate-augmented loops was significantly higher than that of its respective control group. There was no significant difference in stiffness between the 2 reinforcement methods. CONCLUSIONS: Our results suggest that tendon-suture interface reinforcement may improve the pull-out failure strength of a suture construct and thereby increase the effectiveness of stronger suture materials. Future studies might address the effects of different kinds and methods of reinforcement with various suture materials and constructs and in different tissues.
Descriptors: cyanoacrylates, ethyldimethylaminopropyl carbodiimide, suture techniques, sutures, tendon injuries surgery, dogs, injections, materials testing, models, animal, tensile strength.

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