Semi-interpenetrating network of polyethylene glycol and photocrosslinkable chitosan as an in-situ-forming nerve adhesive

An ideal adhesive for anastomosis of severed peripheral nerves should tolerate strains imposed on rejoined nerves. We use blends of photocrosslinkable 4-azidobenzoic acid-modified chitosan (Az-C) and polyethylene glycol (PEG) as a new in-situ-forming bioadhesive for anastomosing and stabilizing the injured nerves. Cryo-scanning electron microscopy suggests that the polymer blends form a semi-interpenetrating network (semi-IPN), where PEG interpenetrates the Az-C network and reinforces it. Az-C/PEG semi-IPN gels have higher storage moduli than Az-C gel alone and fibrin glue. Nerves anastomosed with an Az-C/PEG gel tolerate a higher force than those with fibrin glue prior to failure. A series of ex vivo and in vitro cell experiments indicate the Az-C/PEG gels are compatible with nerve tissues and cells. In addition, Az-C/PEG gels release PEG over a prolonged period, providing sustained delivery of PEG, a potential aid for nerve cell preservation through membrane fusion. Az-C/PEG semi-IPN gels are promising bioadhesives for repairing severed peripheral nerves not only because of their improved mechanical properties but also because of their therapeutic potential and tissue compatibility.