VEGF receptor mRNA expression by ACL fibroblasts is associated with functional healing of the ACL

Abstract

Recent advances in the treatment of ACL ruptures employ platelet-rich plasma combined with collagen to modulate growth factor release from platelets to stimulate healing. Among the most notable of these growth factors is VEGF, which is a potent mitogen and stimulator of vascular growth and healing. However, the effect of such a growth factor on healing depends on the cellular ability to bind with its receptor. The purpose of this study was to test (1) whether the strength of a tissue-engineered ACL repair is associated with VEGF receptors' mRNA expression of ACL cells and (2) whether age influences this association. Nineteen female Yucatan pigs underwent enhanced ACL repair. Biomechanical testing was performed after 15weeks of healing. Messenger RNA of VEGF receptors 1 and 2 in ACL fibroblasts was assessed by RT-PCR. The ACL structural properties were regressed on receptor expression levels in a multivariate model including serum levels of VEGF, age, and weight as potential confounders. While maximum load and linear stiffness were independent of VEGF receptor expression, VEGF receptor 1 was associated with displacement (positively) and yield load (negatively). In a multivariate model of VEGF receptor expression and biomechanics, age was associated with maximum load and yield load. These findings suggest that high VEGF receptor expression, even more so at higher age, results in a more compliant scar, which in turn may lead to greater knee laxity and a compromised clinical result.