ACL Mechanoreceptor Structure and Function Following ACL Surgery

About This Grant

ABSTRACT The project goal is to compare the neural mechanoreceptors of the native anterior cruciate ligament (ACL) to those of the ACL graft after ACL reconstruction surgery (ACLR) and to those of the healing ACL following ACL restoration surgery after 3 months of healing in an established pre-clinical ACL surgery model. ACL tears are common in young and active individuals, and these patients remain at risk for reinjury and posttraumatic osteoarthritis despite ACLR. The reasons for this are unclear and are likely due, in part, to post-surgical neuromuscular deficits. ACLR requires drilling out the ACL insertions and removing the torn ligament before inserting the graft, which disrupts and removes the neural elements of the ACL. Evidence suggests that the neural mechanoreceptors are not restored with healing, which in turn could be responsible for neuromuscular deficits. There has been renewed interest in advancing surgical repair procedures in which the torn ACL is sutured back together to preserve the native insertions and mechanoreceptors of the ACL. We recently translated a novel “ACL restoration” procedure, which combines suture repair with an extracellular matrix-based scaffold saturated with the patient's blood to stimulate healing. We posit that mechanoreceptors in the graft following ACLR are not restored, while those in the ACL following ACL restoration are preserved (Aim 1), and that the neuromuscular function related to those mechanoreceptors (i.e., the ACL-hamstring reflex) is preserved only following ACL restoration (Aim 2). The primary aim (Aim 1) is to compare the number of mechanoreceptors in the healing ACL (i.e., after ACL restoration surgery) and healing graft (i.e., after ACLR surgery) with those of the contralateral ACL-intact control knee at 12 weeks post-op. Twelve individuals will be randomized to undergo either unilateral ACLR or ACL restoration surgery. All ACLs, grafts, and contralateral ACLs will be harvested after 12 weeks and histologically assessed using the neurofilament protein (NFP) and S100 antibodies to identify the mechanoreceptors, which will then be counted and categorized. The primary hypothesis is that there will be fewer mechanoreceptors in the healing graft than in the healing ACL, while the number in the healing ACL will be equivalent to the contralateral intact ACL at 12 weeks. The exploratory aim (Aim 2) is to contrast differences in neuromuscular function at 12 weeks relative to baseline (pre-injury) by evaluating the latency times of the ACL-hamstring reflex arc between knees that undergo ACL restoration versus those that undergo ACLR. The exploratory hypothesis is that the reflex response times for hamstring activation following ACL restoration will be equivalent to baseline and shorter than ACLR at 12 weeks post-op. The results of this study will highlight the mechanoreceptor differences between the healing ACL and healing graft and will provide critical preliminary data to design a preclinical study to establish if the presence or absence of functional mechanoreceptors in the restored ACL or ACLR graft affect neuromuscular control of the knee and modulate PTOA development.