Desenvolvimento e aplicação de copolímero absorvível como câmara de regeneração de nervo periférico em ratos

Abstract

Introduction: Peripheral nerve injury results in functional loss in the innervated organ, and recovery without surgical intervention is rare. Many surgical techniques can be used for nerve repair. Among these, the tubulization technique can be highlighted: this allows regenerative factors to be introduced into the chamber. Biomaterials and neurotrophic factors are indicated as a therapeutic alternative for reconstruction of peripheral nerves. Objective: To develop a nanotextured absorbable tube of poly(lactic-co-glycolic acid), and to evaluate its effect with and without tacrolimus on peripheral nerve regeneration in rats. Materials and Methods: Nanotextured absorbable PLGA tubes and films with and without incorporation of tacrolimus are developed, which were characterized in vitro and in vivo biocompatibility, biodegradability and effectiveness as technical tubing were fabricated. The in vivo experiment in which 88 rats were used, occurred in two stages: the copolymers with and without tacrolimus were implanted in 63 animals to evaluate the biocompatibility; a defect of 10mm sciatic nerve was created in the remaining 25 animals were divided into three groups according to treatment: autograft (5), tubulization with PLGA (10), tubulization with PLGA and tacrolimus (10). Walking Track and histomorphometric analyses were performed. Results: Nanotextured PLGA films, containing tacrolimus or not, differ from the negative control cell viability in vitro assays (p=0.000). The film containing tacrolimus was significantly improved, regardless of the time, when compared to the film without the drug (p=0.026). In vivo biocompatibility evaluation demonstrated a surrounding tissue to PLGA implants with acute inflammation, which was decreasing the long 90 days evaluation. It was evident less collagen deposition in both biomaterials, p ≤ 0.020 seven days after the implants were inserted. The PLGA tube without tacrolimus had smaller average response to the thickness of the myelin sheath compared to autograft and the tube containing tacrolimus in proximal, medial and distal segments (p<0.05). In functional assessment of the recovery of the sciatic nerve in rats, the group of PLGA without tacrolimus significantly differed from the 90 days autograft group (p= 0.0020). Conclusion: The present study suggests that the combination of tacrolimus and PLGA promoted the regeneration of rat sciatic nerves, and this can be a powerful alternative to clinical use in peripheral nerve injuries.