title: Biocompatibility and stability of disulfide-crosslinked hyaluronan films.
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.
authors.affiliation: Department of Medicinal Chemistry, The University of Utah, 419 Wakara Way, Suite 205, Salt Lake City, UT 84108-1257, USA.
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiao
authors.initials: X
authors.lastname: Zheng Shu
authors.forename: Glenn D
authors.initials: GD
authors.lastname: Prestwich
mesh_terms: D020341:Absorbable Implants / Q000009:adverse effects; D000327:Adsorption; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry*; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology*; D005549:Foreign-Body Reaction / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control; D006820:Hyaluronic Acid / Q000737:chemistry*; D020007:Implants, Experimental / Q000009:adverse effects*; D008422:Materials Testing; D008567:Membranes, Artificial; D051379:Mice; D011107:Polylysine / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020099:Coated Materials, Biocompatible; D003432:Cross-Linking Reagents; D004220:Disulfides; D008567:Membranes, Artificial; D011107:Polylysine; D006820:Hyaluronic Acid