Biocompatibility study of biological tissues fixed by a natural compound (reuterin) produced by Lactobacillus reuteri

Glutaraldehyde-fixed biological tissues have been used extensively to fabricate various bioprostheses. However, the tendency for glutaraldehyde to markedly alter tissue stiffness and promote tissue calcification is a well-recognized drawback of this crosslinking agent. To overcome the aforementioned deficiency with the glutaraldehyde-fixed bioprostheses, a fixation technique using a natural compound (reuterin) produced by Lactobacillus reuteri to crosslink biological tissues was developed by our group. It was reported that reuterin inhibits the growth of gram-positive and gram-negative bacteria as well as yeasts, fungi, and protozoa. The study was conducted to evaluate the biocompatibility of the reuterin-fixed tissues with or without ethanol sterilization implanted subcutaneously in a growing rat model. Fresh and the glutaraldehyde-fixed counterparts were used as controls. The results showed that both glutaraldehyde and reuterin are effective antimicrobial agents in the sterilization of biological tissues. The degrees in inflammatory reaction for the reuterin-fixed tissues with or without ethanol sterilization were significantly less than their glutaraldehyde-fixed counterparts throughout the entire course of the study. Additionally, the reuterin-fixed tissues have comparable tensile strengths and resistance against degradation as the glutaraldehyde-fixed tissues. The results obtained at 12-month postoperatively showed that the glutaraldehyde-fixed tissue without ethanol sterilization became significantly stiff and calcified. However, it was found that ethanol sterilization of the glutaraldehyde-fixed tissue may inhibit calcification. Additionally, reuterin fixation may inhibit tissue calcification as compared to glutaraldehyde fixation. These observations implied that the biocompatibility of the reuterin-fixed tissue is superior to the glutaraldehyde-fixed tissue.