부산대학교 도서관

Background: Tissue-engineered blood vessels (TEBV) represent an attractive approach for overcoming reconstructive problems associated with vascular diseases in humankind by providing small caliber vascular grafts. The study evaluates biocompatibility and bioaffinity of vascular prostheses made from chitosan-modified bacterial cellulose (MBC) as potential scaffolds for TEBV.Methods: During the study, acute oral toxicity, up-and-down procedure (UDP), OECD test No. 425 on 10 Imp:WIST rats, intradermal reactivity on three Imp:BN albino rabbits, and sensitization on 15 Imp:DH guinea pigs were performed. The local effects were determined 1 month after intramuscular implantation of prostheses in 30 Imp:WIST rats. Histopathological and pathomorphological studies were conducted following complete removal of implants with peri-implant tissue.Results: There were no signs of toxicity; the median lethal oral dose (LD50) was greater than 2 g/kg body weight for the rats. No allergic reactions were observed in the case of the guinea pig maximization test. Vascular grafts did not induce significant reactive changes in intradermal reactivity test (Main Irritation Index value 0.03) and do not induce inflammatory changes or hyperplasia of the muscle tissue surrounding the implant. Histopathological examination revealed ingrown vascular-connective bands.Conclusions: Tubes made of MBC offer strong potential for use in future TEBV programs for vascular surgery.Lay Summary: Currently, the number of autologous grafts for coronary artery disease and for peripheral artery disease is limited. Particularly materials that will have contact with blood must comply with certain requirements such as mechanical strength, biocompatibility, and no potential to evoke adverse reactions. Bacterial nanocellulose modified with chitosan (MBC) due to its mechanical and biological properties is a promising material for replacing small-diameter vessels grafts. Although previous studies have not shown the toxicity of nanocellulose, we want to check whether medical products based on MBC will be safe when testing in vivo. Thirty Imp:WIST rats and 15 Imp:DH guinea pigs were subject of thorough analysis of potential toxicological and sensitization effect that may develop after applying vascular prostheses made from MBC to living organism. The analysis involved also histopathological and pathomorphological studies following complete removal of implants with peri-implant tissue. The results show that MBC prostheses do not cause any allergic, intradermal reactions and finally, do not display acute toxicity towards the organism in which it is implanted. Moreover, they had not induced inflammatory changes or hyperplasia of the muscle tissue surrounding the implantation sites, thus showing good biocompatibility. Obtained results were discussed with other available studies investigating various aspects of bacterial cellulose or modified bacterial cellulose influence on cells and tissues in both in vitro and in vivo studies. This is the first study analyzing the toxicological and sensitization effect which MBC may evoke and confirm the strong potential for use in future TEBV programs for vascular surgery.Graphical Abstract: