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Biocompatibility and stability of disulfide-crosslinked hyaluronan films

Biomaterials. 2005 Aug;26(23):4737-46. doi: 10.1016/j.biomaterials.2005.01.003.

Abstract

Hyaluronan (HA) can be chemically modified to engineer robust materials with pre-selected mechanical properties and resorption rates that can be dictated by the intended clinical use. Disulfide-crosslinked HA films were prepared by air oxidation of thiol-modified HA, followed by treatment with 0.3% hydrogen peroxide. The degradation of the disulfide-crosslinked films in vitro was very slow (<10% in 7 days) in buffer alone and shorter (t1/2=3-5 days) in the presence of hyaluronidase (HAse). The cytocompatibility of the disulfide-crosslinked HA films was determined using two separate conditions: (i) in vitro culture of mouse fibroblasts in indirect contract with the films, and (ii) in vitro culture of fibroblasts directly on films coated with poly d-lysine. Excellent cytocompatibility was observed in murine fibroblasts that were cultured in indirect contact with thiolated HA films. Although cells were unable to attach and spread on thiolated HA films, pre-coating the thiolated HA films with poly D-lysine resulted in attachment and spreading equivalent to that observed on polystyrene. Rates of resorption in vivo were obtained by subcutaneous implantation of disulfide-crosslinked HA films into the backs of Wistar rats. Biocompatibility in vivo was determined in both subcutaneous flank and peritoneal cavity implantation of the films in Wistar rats. The disulfide-crosslinked HA films were less than 30% resorbed after 42 days in vivo, and histochemical and cytochemical analysis indicated that the films were well-tolerated with mild inflammatory response at both sites of implantation.

Publication types

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

MeSH terms

  • Absorbable Implants / adverse effects
  • Adsorption
  • Animals
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Coated Materials, Biocompatible / chemistry*
  • Cross-Linking Reagents / chemistry
  • Disulfides / chemistry*
  • Fibroblasts / cytology*
  • Fibroblasts / physiology*
  • Foreign-Body Reaction / etiology
  • Foreign-Body Reaction / pathology*
  • Foreign-Body Reaction / prevention & control
  • Hyaluronic Acid / chemistry*
  • Implants, Experimental / adverse effects*
  • Materials Testing
  • Membranes, Artificial
  • Mice
  • Polylysine / chemistry
  • Polylysine / pharmacology
  • Rats
  • Rats, Wistar

Substances

  • Coated Materials, Biocompatible
  • Cross-Linking Reagents
  • Disulfides
  • Membranes, Artificial
  • Polylysine
  • Hyaluronic Acid