X-Message-Number: 11619
Date: Mon, 26 Apr 1999 02:22:09 -0700 (PDT)
From: Doug Skrecky <>
Subject: natural cross-linker

  Sung HW.  Huang RN.  Huang LL.  Tsai CC.  Chiu CT.
  Department of Chemical Engineering, National Central University, Chung-Li,
  Taiwan, Republic of China. 
  Feasibility study of a
  natural crosslinking reagent for biological
  tissue fixation.
  Journal of Biomedical Materials Research.  42(4):560-7, 1998 Dec 15.
  Bioprostheses derived from biological tissues must be chemically modified and
  subsequently sterilized before they can be implanted in humans. Various
  crosslinking reagents, including formaldehyde,
  glutaraldehyde, dialdehyde starch, and epoxy compound, have been used to
  chemically modify biological tissues. However, these synthetic
  crosslinking reagents are all highly (or relatively highly)
  cytotoxic. It is therefore desirable to provide a
  crosslinking reagent suitable for use in biomedical
  applications that is of low cytotoxicity and that forms stable and
  biocompatible crosslinked products. This study evaluates the
  feasibility of using a naturally occurring
  crosslinking reagent--genipin--to chemically modify
  biological tissues. Genipin and its related iridoid compounds, extracted from
  gardenia fruits, have been used in traditional Chinese medicine for the
  treatments of jaundice and various inflammatory and hepatic diseases. In this
  feasibility study, the cytotoxicity of
  genipin and the crosslinking characteristics of
  genipin-fixed biological tissues were investigated. Fresh porcine pericardia
  procured from a slaughterhouse were used as raw materials. Glutaraldehyde and
  an epoxy compound (ethylene glycol diglycidyl ether), which has been used
  extensively in developing bioprostheses, were used as controls. It was found
  that the cytotoxicity of genipin was significantly lower than that of
  glutaraldehyde and the epoxy compound. The amino acid residues in the porcine
  pericardium that may react with genipin were lysine, hydroxylysine, and
  arginine. Additionally, the genipin-fixed tissue had a mechanical strength
  and resistance against enzymatic degradation comparable to the
  glutaraldehyde-fixed tissue. This suggests that genipin can form stable
  crosslinked products. The results of this in vitro study
  demonstrate that genipin is an effective crosslinking
  reagent for biological tissue fixation.

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