Background: Different tendons are chosen for anterior cruciate ligament (ACL) reconstruction based on perceived advantages and disadvantages, yet there is a relative paucity of information regarding biologic responsiveness of commonly used tendon grafts to mechanical strain. Purpose: To evaluate the in vitro responses of graft fibroblasts derived from tendons used for ACL reconstruction to clinically relevant strain levels. Study Design: Controlled laboratory study. Methods: Twelve quadriceps tendons (QTs), 12 patellar tendons (PTs), and 9 hamstring tendons (HTs) were harvested from skeletally mature dogs (n = 16). Tendon fibroblasts were isolated and seeded onto BioFlex plates (1 × 105 cells/well). Cells were subjected to 3 strain conditions (stress deprivation, 0%; physiologic, 4%; high, 10%) for 5 days. Media were collected for proinflammatory and metabolic assays. RNA was extracted for gene expression analysis using real-time reverse transcription polymerase chain reaction. Results: Stress deprivation elicited significantly higher metabolic activity from HT and PT cells than from QT cells ( P < .001 and P = .001, respectively). There were no differences in metabolic activity among all 3 graft fibroblasts at physiologic and high strain. COL-1 expression was significantly higher in PT versus HT during physiologic strain ( P = .007). No significant differences with COL-3 expression were seen. TIMP-1 ( P = .01) expression was higher in PT versus HT under physiologic strain. Scleraxis expression was higher in PT versus HT ( P = .007) under physiologic strain. A strain-dependent increase in PGE2 levels occurred for all grafts. At physiologic strain conditions, HT produced significantly higher levels of PGE2 versus QT ( P < .001) and PT ( P = .005). Conclusion: Fibroblasts from common ACL graft tissues exhibited different metabolic responses to mechanical strain. On the basis of these data, we conclude that early production of extracellular matrix and proinflammatory responses from ACL grafts are dependent on mechanical loading and graft source. Clinical Relevance: Graft-specific differences in ACL reconstruction outcomes are known to exist. Our results suggest that there are differences in the biologic responsiveness of cells from the tendon grafts used in ACL reconstruction, which are dependent on strain levels and graft source. The biologic properties of the tissue used for ACL reconstruction should be considered when selecting graft source.
Anterior cruciate ligament (ACL) injuries are common knee ligament injuries. While generally successful, ACL reconstruction that uses a tendon graft to stabilize the knee is still associated with a notable percentage of failures and long‐term morbidities. Preclinical research that uses small laboratory species (i.e., mice, rats, and rabbits) to model ACL reconstruction are important to evaluate factors that can impact graft incorporation or posttraumatic osteoarthritis after ACL reconstruction. Small animal ACL reconstruction models are also used for proof‐of‐concept studies for the development of emerging biological strategies aimed at improving ACL reconstruction healing. The objective of this review is to provide an overview on the use of common small animal laboratory species to model ACL reconstruction. The review includes a discussion on comparative knee anatomy, technical considerations including types of tendon grafts employed amongst the small laboratory species (i.e., mice, rats, and rabbits), and common laboratory evaluative methods used to study healing and outcomes after ACL reconstruction in small laboratory animals. The review will also highlight common research questions addressed with small animal models of ACL reconstruction.
Background The accumulation of cartilage breakdown products in body fluids has been extensively investigated to assess the accuracy of molecular biomarkers from a diagnostic, prognostic, and therapeutic perspective. Nevertheless, to the authors' knowledge, there is a lack of information about spontaneous models of hip osteoarthritis and the differentiating ability of collagen, noncollagen, and inflammatory biomarkers. Objectives We aimed to assess the accuracy of four plasma biomarkers that could differentiate between healthy dogs and dogs with hip dysplasia. Methods Twenty‐four dogs were used in this institutionally approved study (12 in the mild to severe hip dysplasia group; 12 in the control group). Plasma concentrations of biomarkers were compared. The ability of each marker to differentiate control from diseased dogs was assessed using an independent t‐test, logistic regression, and receiving operating characteristics (ROC) analysis. Results Three biomarkers were significantly different between the two groups. The collagen marker procollagen type II propeptide (PIICP) was useful in differentiating between control and diseased dogs with the best combination of sensitivity and specificity. The four biomarkers showed high area under the curve (AUC) values. Conclusions The results indicate that plasma biomarkers can be used as a screening tool for canine hip dysplasia. Although the cutoff values and diagnostic ability of the biomarkers used in this study show promising results, the sources of individual variability should be addressed. Future studies with larger groups of dogs are needed to correlate plasma levels in serum and synovial fluid during clinical disease.
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