Mineral Coated Microparticle Sutures Impregnated With GDNF (Glial Derived Neurotrophic Factor) and NGF (Nerve Growth Factor) Improve Axonal Growth and Functional Recovery in Rat Sciatic Nerve Injuries

INTRODUCTION Autologous nerve grafts and end-to-end neurorrhaphy are considered the gold standard for large nerve gaps (ie, > 5 mm gaps) for peripheral nerve injury repair. During nerve regeneration, the local presence of growth factors plays an important role. In order to aid in delivery of growth factors, we have modified standard surgical micro-sutures with calcium phosphate (CaP) coatings, which we have designed to deliver cytokines in a temporally modulated manner, specifically glial derived neurotrophic factor (GDNF) and nerve growth factor (NGF). In this study, rat sciatic nerve injury is repaired with autograft with sutures coated with GDNF and NGF with the goal of promoting more axonal growth and improved functional outcomes compared to control rats repaired with non-coated suture. METHODS To create the injury, all rats had 6 mm of the right sciatic nerve removed, and then a 10 mm isograft from a donor rat micro-sutured end-to-end with 2 standard 9-0 Nylon sutures on the proximal end and two sutures of the correct treatment on the distal end. There were 5 groups (control, CaP only, GDNF, NGF and GDNF + NGF), each group consisted of 6 to 8 rats. Functional testing was done weekly for each rat from week 5 to 12 post repair. The experiment was terminated at 12 wk and axonal growth was assessed with electron microscopy RESULTS Rats treated with mineral coated microparticle (MCM) sutures coated with GDNF + NGF had significantly increased (P = .0014) axonal counts (mean: 8511) in the sciatic nerve distal to neurorrhaphy compared to controls (mean: 5123). Functional testing as measured by ankle contracture, showed statistically significant improvement (P = .0014) starting at week 7 and continuing to week 12 compared to control groups. CONCLUSION MCM sutures releasing GDNF increase the amount of axons in the graft and distal to the graft. MCMs releasing NGF and GDNF increase functional recovery after week 7.