A Dual-network Nerve Adhesive with Enhanced Adhesion Strength Promotes Transected Peripheral Nerve Repair.

Abstract

Peripheral nerve transection has a high prevalence and results in functional loss of affected limbs. The current clinical treatment using suture anastomosis significantly limits nerve recovery due to severe inflammation, secondary damage, and fibrosis. Fibrin glue, a commercial nerve adhesive as an alternative, avoids secondary damage but suffers from poor adhesion strength. To address their limitations, a highly efficacious nerve adhesive based on dual-crosslinking of dopamine-isothiocyanate modified hyaluronic acid and decellularized nerve matrix is reported in this paper. This dual-network nerve adhesive (DNNA) shows controllable gelation behaviors feasible for surgical applications, robust adhesion strength, and promoted axonal outgrowth in vitro. The in vivo therapeutic efficacy is tested using a rat-based sciatic nerve transection model. The DNNA decreases fibrosis and accelerates axon/myelin debris clearance at 10 days post-surgery, compared to suture and commercial fibrin glue treatments. At 10 weeks post-surgery, the strong adhesion and bioactivity allow DNNA to significantly decrease intraneural inflammation and fibrosis, enhance axon connection and remyelination, aid motor and sensory function recovery, as well as improve muscle contraction, compared to suture and fibrin treatments. Overall, this dual-network hydrogel with robust adhesion provides a rapid and highly efficacious nerve transection treatment to facilitate nerve repair and neuromuscular function recovery.