Fibroblasts From Common Anterior Cruciate Ligament Tendon Grafts Exhibit Different Biologic Responses to Mechanical Strain

Abstract

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.