Summary
Background
A common approach for tissue regeneration is cell delivery, for example by direct transplantation of stem or progenitor cells. An alternative, by recruitment of endogenous cells, needs experimental evidence. We tested the hypothesis that the articular surface of the synovial joint can regenerate with a biological cue spatially embedded in an anatomically correct bioscaffold.
Methods
In this proof of concept study, the surface morphology of a rabbit proximal humeral joint was captured with laser scanning and reconstructed by computer-aided design. We fabricated an anatomically correct bioscaffold using a composite of poly-ε-caprolactone and hydroxyapatite. The entire articular surface of unilateral proximal humeral condyles of skeletally mature rabbits was surgically excised and replaced with bioscaffolds spatially infused with transforming growth factor β3 (TGFβ3)-adsorbed or TGFβ3-free collagen hydrogel. Locomotion and weightbearing were assessed 1–2, 3–4, and 5–8 weeks after surgery. At 4 months, regenerated cartilage samples were retrieved from in vivo and assessed for surface fissure, thickness, density, chondrocyte numbers, collagen type II and aggrecan, and mechanical properties.
Findings
Ten rabbits received TGFβ3-infused bioscaffolds, ten received TGFβ3-free bioscaffolds, and three rabbits underwent humeral-head excision without bioscaffold replacement. All animals in the TGFβ3-delivery group fully resumed weightbearing and locomotion 3–4 weeks after surgery, more consistently than those in the TGFβ3-free group. Defect-only rabbits limped at all times. 4 months after surgery, TGFβ3-infused bioscaffolds were fully covered with hyaline cartilage in the articular surface. TGFβ3-free bioscaffolds had only isolated cartilage formation, and no cartilage formation occurred in defect-only rabbits. TGFβ3 delivery yielded uniformly distributed chondrocytes in a matrix with collagen type II and aggrecan and had significantly greater thickness (p=0·044) and density (p<0·0001) than did cartilage formed without TGFβ3. Compressive and shear properties of TGFβ3-mediated articular cartilage did not differ from those of native articular cartilage, and were significantly greater than those of cartilage formed without TGFβ3. Regenerated cartilage was avascular and integrated with regenerated subchondral bone that had well defined blood vessels. TGFβ3 delivery recruited roughly 130% more cells in the regenerated articular cartilage than did spontaneous cell migration without TGFβ3.
Interpretation
Our findings suggest that the entire articular surface of the synovial joint can regenerate without cell transplantation. Regeneration of complex tissues is probable by homing of endogenous cells, as exemplified by stratified a vascular cartilage and vascularised bone. Whether cell homing acts as an adjunctive or alternative approach of cell delivery for regeneration of tissues with different organisational complexity warrants further investigation.
Funding
New York State Stem Cell Science; US National In...
We propose standardized definitions and criteria for documenting subjective results for clinical orthopedic studies in veterinary medicine. To our knowledge, no common terminology or basis for describing results in this manner has been published. This lack of standardization limits our abilities to communicate study results in a consistent manner, interpret data appropriately, and compare results across studies, centers, and techniques. An initial step toward addressing these deficiencies is to provide clear definitions and criteria for time frames of data collection, subjective outcomes, and complications. These definitions and criteria are recommended for use based on consensus among the authors who have experience and expertise in small animal and equine orthopedic clinical research. Our hope is that this terminology will be implemented so that data collection and reporting are more consistent and effective in veterinary orthopedic reports.
BACKGROUND
OBJECTIVE-To evaluate prevalence of and risk factors for hip dysplasia (HD) and cranial cruciate ligament deficiency (CCLD) in dogs and determine change in prevalence over time. DESIGN-Cross-sectional study. ANIMALS-1,243,681 Dogs for which information was reported to the Veterinary Medical Database between 1964 and 2003. PROCEDURES-Information on breed, sex, and age was collected, and prevalences and odds ratios were calculated. RESULTS-Castrated male dogs were significantly more likely than other dogs to have HD (odds ratio [OR], 1.21), and castrated male (OR, 1.68) and spayed female (OR, 2.35) dogs were significantly more likely to have CCLD. Dogs up to 4 years old were significantly more likely to have HD (OR for dogs 2 months to 1 year old, 1.22; OR for dogs > 1 to 4 years old, 1.48), whereas dogs > 4 years old were significantly more likely to have CCLD (OR for dogs > 4 to 7 years old, 1.82; OR for dogs > 7 years old, 1.48). In general, large- and giant-breed dogs were more likely than other dogs to have HD, CCLD, or both. Prevalences of HD and CCLD increased significantly over the 4 decades for which data were examined. CONCLUSIONS AND CLINICAL RELEVANCE-Results suggested that sex, age, and breed were risk factors for HD, CCLD, or both in dogs and that prevalences of HD and CCLD have increased over time.
The dog is a common model for study of osteoarthritis (OA). Subjective histologic scoring systems have often served as the reference standard for presence and severity of OA. However, these scoring systems have perceived shortcomings. The system developed for this report attempts to address these shortcomings by providing a standardized methodology for global assessment of the joint, versatility and the potential for relative weighting of pathology, allowing for comparison among time points, studies, and centers, and critical analysis of the system's reliability. The proposed system for assessment of canine tissues appears to provide an effective method for global assessment of articular pathology in OA. The system is versatile, comprehensive, and reliable and appears to have advantages over conventional scoring systems.
Dome osteotomies can be used to correct radial deformities in the frontal and sagittal planes, with certain advantages, but are heavily reliant on appropriate preoperative planning.
The established method of measurement and references ranges can be used to aid in diagnosis, determining indications, and surgical planning for angular limb deformities of the tibia, especially when affected bilaterally. The methodology and reference values may also be used for postoperative critique.
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