Disulfide-crosslinked hyaluronan-gelatin sponge: Growth of fibrous tissue in vivo
Disulfide-crosslinked hyaluronan-gelatin sponge: Growth of fibrous tissue in vivo
Nov 2003
Received: 23 January 2003; Revised: 18 April 2003; Accepted: 21 July 2003
Yanchun Liu 1, Xiao Zheng Shu 1, Steven D. Gray 2, Glenn D. Prestwich 1 *
Journal of Biomedical Materials Research Part A
Volume 68A, Issue 1 , Pages 142 - 149
Wiley InterScience
1Department of Medicinal Chemistry, The University of Utah, 419 Wakara Way, Suite 205, Salt Lake City, Utah 84108-1257
2Department of Otolaryngology, The University of Utah, 30 North Medical Drive, 3C120, Salt Lake City, Utah 84132-230

email: Glenn D. Prestwich (gprestwich@pharm.utah.edu)
*Correspondence to Glenn D. Prestwich, Department of Medicinal Chemistry, The University of Utah, 419 Wakara Way, Suite 205, Salt Lake City, Utah 84108-1257
Deceased.
Funded by:
The University of Utah (to G.D.P.)
National Institutes of Health; Grant Number: DC 04336 (to S.D.G. and G.D.P.)
Keywords
cell growth ? macroporous sponge ? human tracheal scar fibroblasts ? thiol modification ? lyophilized scaffold
Abstract
The modification of hyaluronan (HA) and gelatin using dithiobis(propanoic dihydrazide) (DTP) has provided two thiolated macromolecular components of the extracellular matrix (ECM), specifically HA-DTPH and gelatin-DTPH. Blends of these thiolated ECM components were crosslinked in air to form hydrogels that were interpenetrating disulfide-crosslinked networks. Lyophilization of the hydrogels afforded sponge-like macroporous scaffolds suitable for cell attachment and proliferation. Increasing percentages of gelatin-DTPH (0, 25, 50, and 75%) were blended with HA-DTPH, and the resulting sponges were evaluated in vitro and in vivo as scaffolds for tissue engineering by seeding with human tracheal scar (HTS) fibroblasts. While cells failed to attach and grow in HA-only sponges, the gelatin-modified HA sponges promoted cell adhesion, proliferation, and spreading in vitro. Optimal attachment and growth was observed with 50% gelatin-HA sponges. Cell attachment to the gelatin-HA sponge could be blocked by preincubation of cells with a soluble fibronectin peptide Gly-Arg-Gly-Asp (GRGD). Finally, HTS fibroblast-seeded gelatin-HA sponges were implanted into the flanks of nude mice and evaluated at 2 and 8 weeks postimplantation. The sponges were fully biocompatible and new fibrous tissue formed, gradually replacing the sponge-like scaffold. The gelatin-HA sponges act as synthetic, macroporous, covalent mimics of the ECM and constitute novel scaffolds for cell growth and tissue augmentation. ? 2003 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 142-149, 2004
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