33 ABSTRACT The present disclosure provides delivery systems for delivering FK506 locally to damaged nerve sites. Particulate FK506 incorporated into a fibrin gel, with the amount of FK506 sufficient to give an FK506 release rate over at least 14 days of at least 5 micrograms per milliliter of the treated tissue per day has been shown to remarkably improve axon regeneration. The delivery systems include particulate FK506 having sizes between about 500 microns to about 1 millimeter encapsulated in a fibrin matrix, powdered FK506 encapsulated within electrospun films, powdered FK506 encapsulated within a cellulose matrix, and a flexible film of small intestinal submucosa having a plurality of solid islands located on one side thereof, with each island containing a preselected amount of FK506 and a polyester. The local application of FK506 via the local delivery system disclosed herein results in excellent nerve regeneration while preventing the toxicity of systemic FK506 that has prevented clinicians from using FK506 routinely for treating severe cases of peripheral nerve injuries. In addition to being used for treatment of damaged nerve sites, the present systems may be applied to other types of injuries, including but not limited to spinal cord Injuries, stroke, vascularized composite allotransplantation (VCA) and local applications during solid organ transplants.
