Bacterial Cellulose/Cellulose Acetate Composites With Micro-nano Structure As Biomimetic Small Diameter Vascular Scaffolds:Design,Synthesis And Properties

Millions of vascular transplant operations have been successful completion every year,especially in large diameter vascular transplant.In contrast,the success rate in small diameter artificial vascular grafts(<6 mm)is very low.This is because the shearing force between the blood and material becomes too weak,and lack growth potential in small diameter artificial vascular grafts,which make the small diameter artificial vascular grafts suffer serious complications like thrombosis formation and development of neointimal hyperplasia at the anastomosis sites with increasing the probability of thrombus.So,the small artificial blood vessel requires better hemocompatibility.As we all know,human natural blood vessels have excellent blood compatibility.Therefore,the preparation of small diameter artificial vascular grafts by simulating the structure of natural blood vessels has become the main research direction.biomimetic scaffolds resembling important features of native blood vessels including dimension,composition,structure,and mechanical properties are found to be of most interest in vascular tissue engineering.In this work,we developed a bionic small-diameter vascular scaffold with a micro-nano structure which has biomimetic structures and functions of natural blood vessels via combining the electrospinning technology and the membrane-liquid interface culture method to mimic the structure and function of natural blood vessels.First,we prepared a scaffold with micron-fibrous structure via electrospinning method.Then,BC nanofibers grew in-situ in cellulose acetate micro-fibrous scaffolds via step by step biosynthesis method.Finally,a series of micro-nano fibrous scaffolds(BC/CA)with biomimetic vascular inner structure with different porosity were obtained.The microscopic morphology,crystal structure,mechanical properties,blood compatibility and biocompatibility of these composites were evaluated.The results indicated that the overall performance of BC/CA composites are better than those of BC or CA.Among the BC/CA composites which contain different contents of BC,BC/CA-2has best hemocompatibility: It not only has good effect on promoting proliferation of endothelial cells,but also can promote the endothelialization of cells.Compared to other BC/CA composites which contains different contents of BC,BC/CA-2 possesses a better cell compatibility,inducing less inflammatory reactions in vivo.In order to improve the blood compatibility of scaffold materials and promote the endothelialization of cells,BC/CA-Hep was prepared upon introducing heparin into BC/CA-2via condensation reaction catalyzed by EDC and NHS.The effects of heparin on themorphology,mechanical properties,wettability,chemical structure,crystal structure,and hemocompatibility of the composites were explored.The effects of heparin on the biocompatibility of cells,such as morphology and proliferation,were further studied.SEM test results show that the introduction of Hep doesn’t change the micro morphology of the material.Compared with BC/CA,the tensile strength of BC/CA-Hep is increased by 19%.The results of blood and cell experiments showed that the introduction of Hep significantly reduced the platelet adhesion,improved the blood compatibility of the materials,and effectively promoted the endothelialization of the cells.In conclusion,BC/CA-Hep has potential to be used for clinical small diameter artificial vascular grafts,alleviating the poor status of blood vessel transplantation.