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

J Biomed Mater Res A. 2006 Dec 15;79(4):902-12. doi: 10.1002/jbm.a.30831.


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 ( approximately 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.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Biocompatible Materials* / chemistry
  • Biocompatible Materials* / pharmacology
  • Chondroitin Sulfates / chemistry
  • Chondroitin Sulfates / pharmacology
  • Evaluation Studies as Topic
  • Extracellular Matrix* / chemistry
  • Fibroblasts / cytology
  • Fibroblasts / transplantation
  • Gelatin / chemistry
  • Gelatin / pharmacology*
  • Hyaluronic Acid / chemistry
  • Hyaluronic Acid / pharmacology
  • Hydrogels / chemical synthesis*
  • Hydrogels / chemistry
  • Hydrogels / pharmacology
  • Materials Testing / methods
  • Mice
  • Mice, Nude
  • NIH 3T3 Cells
  • Tissue Engineering / methods


  • Adjuvants, Immunologic
  • Biocompatible Materials
  • Hydrogels
  • Gelatin
  • Hyaluronic Acid
  • Chondroitin Sulfates