Synthesis and evaluation of injectable, in situ crosslinkable synthetic extracellular matrices for tissue engineering

  1. Xiao Zheng Shu1,
  2. Shama Ahmad2,
  3. Yanchun Liu1,
  4. Glenn D. Prestwich1,2,*

Article first published online: 29 AUG 2006

DOI: 10.1002/jbm.a.30831

Issue

Journal of Biomedical Materials Research Part A

Journal of Biomedical Materials Research Part A

Volume 79A, Issue 4, pages 902–912, 15 December 2006

Additional Information

How to Cite

Shu, X. Z., Ahmad, S., Liu, Y. and Prestwich, G. D. (2006), Synthesis and evaluation of injectable, in situ crosslinkable synthetic extracellular matrices for tissue engineering. Journal of Biomedical Materials Research Part A, 79A: 902–912. doi: 10.1002/jbm.a.30831

Author Information

  1. 1

    Center for Therapeutic Biomaterials and Department of Medicinal Chemistry, The University of Utah, 419 Wakara Way, Suite 205, Salt Lake City, Utah 84108-1257

  2. 2

    Department of Bioengineering, The University of Utah, 20 South 2030 East, Room 144, Salt Lake City, Utah 84112

*Center for Therapeutic Biomaterials and Department of Medicinal Chemistry, The University of Utah, 419 Wakara Way, Suite 205, Salt Lake City, Utah 84108-1257

Publication History

  1. Issue published online: 7 NOV 2006
  2. Article first published online: 29 AUG 2006
  3. Manuscript Accepted: 14 MAR 2006
  4. Manuscript Revised: 27 FEB 2006
  5. Manuscript Received: 15 NOV 2005

Funded by

  • NIH. Grant Numbers: 1R01 DC04663, 2R01 DC04663
  • NSF FIBR. Grant Number: EF 0526854
  • The University of Utah
  • The Center for Therapeutic Biomaterials

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Keywords:

  • glycosaminoglycan;
  • covalent crosslinker;
  • regenerative medicine;
  • 3D cell culture;
  • hydrogel;
  • hyaluronan;
  • chondroitin sulfate

Abstract

Simple and effective biocompatible materials that mimic the natural extracellular matrix (ECM) were developed for a variety of uses in regenerative medicine. These synthetic ECMs (sECMs) were designed to recapitulate the minimal composition required to obtain functional ECMs. The sECM components are crosslinkable in situ, and may be seeded with cells prior to injection in vivo, without compromising either the cells or the recipient tissues. Several sECM compositions were evaluated to establish which formulation would be most beneficial for cell growth and tissue remodeling. Three natural ECM macromonomeric building blocks were employed: hyaluronan (HA), chondroitin sulfate (CS), and gelatin (Gtn). The carboxyl-rich glycosaminoglycans and Gtn were each chemically modified to give the corresponding thiolated dithiopropionylhydrazide (DTPH) derivatives (CS-DTPH, HA-DTPH, and Gtn-DTPH). Different compositions of CS-Gtn and HA-Gtn hydrogels were fabricated by crosslinking the thiolated biomacromonomers with polyethylene glycol diacrylate. Each sECM had high water content (>96%), biologically suitable mechanical properties, and a useful gelation time (∼2–6 min). The bioerosion rates for the sECMs were determined, and a given composition could be selected to meet the requirements of a given clinical application. Both the HA-Gtn and CS-Gtn sECM hydrogels supported cell growth and proliferation with cultured murine fibroblasts in vitro. Moreover, subcutaneous injection of a suspension of murine fibroblasts in each of the two sECM hydrogels into nude mice in vivo resulted in the formation of viable and uniform soft tissue in vivo. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006

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