A Tacrolimus-Releasing Nanofiber Nerve Wrap to Enhance Motor and Sensory Recovery in Injured Peripheral Nerves
Abstract
Background and Objectives: Nerve injuries from penetrating or blunt trauma often result in lifelong disability with loss of sensation and paralysis. Recovery is usually poor. A key barrier to recovery is the naturally slow axonal regeneration rate which consequently deprives the target muscle and skin of nerve supply and results in permanent loss of function. Drug-based therapies that accelerate axonal regeneration may decrease the denervation time and thereby improve functional recovery. However, no such treatments to augment the results of surgery are currently available. Local delivery of the transplant antirejection drug, also known as tacrolimus, via biodegradable gels to the nerve repair site results in enhanced nerve regeneration. A more convenient, surgeon-friendly delivery system is needed for clinical use in the operating room. We aim to validate a reliable, effective, and easy-to-use, off-the-shelf product for local drug delivery following nerve surgery and demonstrate its effectiveness. We have therefore designed a biodegradable wrap for the delivery of tacrolimus that surgeons can place around the site of injured nerves during surgery. Methods: We will fabricate nerve wraps made out of polymers sheets loaded with tacrolimus. Based on our preliminary studies on gel-based application of tacrolimus, these devices will provide sustained tacrolimus release to the nerve repair site for 4 weeks or longer. We will assess effectiveness in a rat model by wrapping the devices around nerve repair sites. Adult rats will undergo hindlimb nerve transection and immediate repair. Intraoperatively, rats will receive either the nerve wrap loaded with tacrolimus (local treatment), an empty nerve wrap without tacrolimus, daily subcutaneous tacrolimus injections, or undergo nerve repair only as a control group. After 21 days, we will assess the number of sensory and nerve cells that regenerate to the skin and muscle using tracer dyes. To determine the effect of local tacrolimus delivery on recovery of movement rats will undergo unilateral median (forearm) nerve cut and repair and will be randomly allocated to tacrolimus nerve wrap treatment or vehicle alone. Time to return of active finger flexion is monitored by daily grasping tests. Anticipated Results: We anticipate that the devices will increase the number of nerve regeneration to the muscle and skin, resulting in improved and accelerated functional recovery. The results will form the basis for human device trials to enhance outcomes following nerve trauma.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310081
Entities
People
- Gregory Borschel
Organizations
- Indiana University
- United States Army