Crosslinking characteristics of an epoxy-fixed porcine tendon: Effects of pH, temperature, and fixative concentration

Sung, Hsing‐Wen; Hsu, Chin-Sheng; Lee, Yuag-Shein; Lin, Der-Shyu

doi:10.1002/(sici)1097-4636(199608)31:4<511::aid-jbm11>3.0.co;2-j

Cited by 62 publications

(30 citation statements)

References 26 publications

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“…The reaction mechanisms of biological tissues with epoxy compound under acidic and basic conditions have been previously described in the literature. 21 The reaction mechanism of amino acids or proteins with genipin is still not well understood at present. As illustrated in Figure 8, genipin has a cyclic hemi-acetal skeleton that is structurally equivalent to a dialdehyde in the presence of water.…”

Section: Discussionmentioning

confidence: 99%

Feasibility study of a natural crosslinking reagent for biological tissue fixation

Sung

Huang

et al. 1998

J. Biomed. Mater. Res.

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292

249

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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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Section: Discussionmentioning

confidence: 99%

Feasibility study of a natural crosslinking reagent for biological tissue fixation

Sung

Huang

et al. 1998

J. Biomed. Mater. Res.

Self Cite

292

249

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“…This technique was widely used in studying the thermal transitions of collagenous tissues 26, 27. Details of the methodology used in the measurement of denaturation temperature were previously described 28…”

Section: Methodsmentioning

confidence: 99%

Feasibility study using a natural compound (reuterin) produced by Lactobacillus reuteri in sterilizing and crosslinking biological tissues

Chen

Sung

Liang

et al. 2002

J. Biomed. Mater. Res.

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Bioprostheses derived from biological tissues have to be fixed and subsequently sterilized before they can be implanted in humans. Currently available crosslinking agents and sterilants used in the fixation or sterilization of biological tissues such as glutaraldehyde and formaldehyde are all highly cytotoxic, which may impair the biocompatibility of bioprostheses. Therefore, it is desirable to provide an agent suitable for use in biomedical applications that is of low cytotoxicity and may form sterile and biocompatible crosslinked products. To achieve this goal, a natural compound (reuterin), produced by Lactobacillus reuteri in the presence of glycerol, was used by our group. It is known that reuterin has antibacterial, antimycotic, and antiprotozoal activities. Additionally, as in the case with formaldehyde, reuterin may react with the free amino groups in biological tissues by using its aldehyde functional group. Therefore, it was speculated that reuterin could be used as a crosslinking agent and a sterilant for biological tissues in the same way as glutaraldehyde and formaldehyde. In the study, the production of reuterin, produced by Lactobacillus reuteri under control conditions, was reported. Preparative chromatography was used to purify reuterin. Also, the minimal inhibitory concentration and minimal bactericidal concentration of reuterin and its antimicrobial activity on a contaminated tissue were investigated. In addition, the cytotoxicity of reuterin was evaluated. Glutaraldehyde, the most commonly used sterilant in the sterilization of biological tissues, was employed as a control. Furthermore, the feasibility of using reuterin as a crosslinking agent in fixing biological tissues was studied. Fresh and the glutaraldehyde-fixed tissues were used as controls. The results obtained in the minimal inhibitory concentration and minimal bactericidal concentration studies and in the sterilization study of a contaminated tissue indicated that the antimicrobial activity of reuterin is significantly superior to its glutaraldehyde counterpart. In addition, the results obtained in the 3-(4,5-dimethylthiazol-yl)-2,5-diphenyltetrazolium bromide assay showed that reuterin is significantly less cytotoxic than glutaraldehyde. Additionally, it was found that reuterin is an effective crosslinking agent for biological tissue fixation. The reuterin-fixed tissue had comparable free amino group content, denaturation temperature, and resistance against enzymatic degradation as the glutaraldehyde-fixed tissue. In conclusion, the results obtained in this study indicate that reuterin is an effective agent in the sterilization and fixation of biological tissues.

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“…5 Genipin has also been studied for its anti-inflammatory effects, administered either directly to different cell lines 10,11 or orally to animals. 12,13 Moreover, genipin cross-linking has been shown to affect the mechanical properties of biological tissues, increasing the tensile strength of bovine pericardium, 14 porcine tendon, 15 and type I collagen gels. 16 Our laboratory uses agarose hydrogel as a scaffold system for cartilage tissue engineering.…”

Section: Introductionmentioning

confidence: 99%

Genipin enhances the mechanical properties of tissue‐engineered cartilage and protects against inflammatory degradation when used as a medium supplement

Lima

Tan

Tai

et al. 2008

J Biomedical Materials Res

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Neurofibromatosis type 1 (NF1) is an autosomal dominant condition with a birth incidence of 1/3,500. Around 50% of cases are due to new mutations. The NF1 gene maps to 17q11.2 and encodes neurofibromin. NF1 is a “classical” tumor suppressor gene. Congenital disseminated NF1 is rare with just two cases previously reported. We present a deceased baby with congenital disseminated NF1 in whom we performed molecular studies. A germline mutation (R461X) in exon 10a of the NF1 gene was found. A 2 bp deletion (3508delCA) in codon 1170 of exon 21 was identified in DNA derived from some tumor tissue. Loss of heterozygosity in NF1 and TP53 was observed in other tumor samples. No microsatellite instability was observed in the tumor samples. This is the first report of molecular analysis of the NF1 locus in a patient with disseminated congenital neurofibromatosis. This case had a de novo germline mutation in NF1 and three documented somatic mutations in the NF1 and TP53 genes in tumor specimens. © 2008 Wiley‐Liss, Inc.

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Crosslinking characteristics of an epoxy-fixed porcine tendon: Effects of pH, temperature, and fixative concentration

Cited by 62 publications

References 26 publications

Feasibility study of a natural crosslinking reagent for biological tissue fixation

Feasibility study of a natural crosslinking reagent for biological tissue fixation

Feasibility study using a natural compound (reuterin) produced by Lactobacillus reuteri in sterilizing and crosslinking biological tissues

Genipin enhances the mechanical properties of tissue‐engineered cartilage and protects against inflammatory degradation when used as a medium supplement

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