Rapidly photo-cross-linkable chitosan hydrogel for peripheral neurosurgeries

Biomacromolecules. 2011 Jan 10;12(1):57-65. doi: 10.1021/bm101004r. Epub 2010 Dec 3.

Abstract

Restoring continuity to severed peripheral nerves is crucial to regeneration and enables functional recovery. However, the two most common agents for coaptation, sutures and fibrin glues, have drawbacks such as inflammation, pathogenesis, and dehiscence. Chitosan-based adhesives are a promising alternative, reported to have good cytocompatibility and favorable immunogenicity. A photo-cross-linkable hydrogel based on chitosan is proposed as a new adhesive for peripheral nerve anastomosis. Two Az-chitosans were synthesized by conjugating 4-azidobenzoic acid with low (LMW, 15 kDa) and high (HMW, 50-190 kDa) molecular weight chitosans. These solutions formed a hydrogel in less than 1 min under UV light. The LMW Az-chitosan was more tightly cross-linked than the HMW variant, undergoing significantly less swelling and possessing a higher rheological storage modulus, and both Az-chitosan gels were stiffer than commercial fibrin glue. Severed nerves repaired by Az-chitosan adhesives tolerated longitudinal forces comparable or superior to fibrin glue. Adhesive exposure to intact nerves and neural cell culture showed both Az-chitosans to be nontoxic in the acute (minutes) and chronic (days) time frames. These results demonstrate that Az-chitosan hydrogels are cytocompatible and mechanically suitable for use as bioadhesives in peripheral neurosurgeries.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azides / chemistry*
  • Chitosan* / chemistry
  • Chitosan* / pharmacology
  • Cross-Linking Reagents / chemistry*
  • Humans
  • Hydrogels* / chemical synthesis
  • Hydrogels* / chemistry
  • Hydrogels* / pharmacology
  • Male
  • Materials Testing
  • Neurosurgical Procedures / methods
  • PC12 Cells
  • Peripheral Nerve Injuries
  • Peripheral Nerves / surgery*
  • Photochemistry / methods
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Adhesives* / chemistry
  • Tissue Adhesives* / pharmacology
  • Ultraviolet Rays

Substances

  • Azides
  • Cross-Linking Reagents
  • Hydrogels
  • Tissue Adhesives
  • 4-azidobenzoic acid
  • Chitosan