Engineering the shape of bacterial cellulose and its use as blood vessel replacement

Doktorsavhandling, 2008

Tissue loss and organ failure are major health problems that impose great costs on society. Cardiovascular diseases are responsible for 36% of mortalities and the disease burden among adults over the age of 60. The single largest cardiovascular disease is atherosclerosis in the coronary artery. Methods of treatment depend upon its severity and include drug therapy, coronary artery angioplasty and coronary bypass grafting.Approximately every tenth patient unfortunately lacks native replacement vessels. Synthetic grafts based on polyester or expanded polytetrafluoroethylene work satisfactorily at diameters larger than 6mm, but they become occluded as a result of thrombosis when smaller diameters are used. Despite enormous efforts, scientists have yet not found a suitable solution. Tissue engineered blood vessels (TEBV) represent an attractive approach for overcoming reconstructive problems associated with vascular diseases by providing small calibre vascular grafts. The aim of this study was to evaluate a novel biosynthetic biomaterial, bacterial cellulose (BC), as a potential graft and as a scaffold for TEBV. Biopolymers are a family of materials that we think can be used to mimick structures in the human body. BC is a biopolymer excreted by Acetobacter Xylinum into a network of nanofibrils. We found that the dimensions and morphology of cellulose nanofibrils were similar to those of collagen. By creating an interface between air and culture medium in different shapes, we were able to alter the shape of the resulting biomaterial. We found that the mechanical properties of bacterial cellulose are far more similar to those of collagen in a blood vessel than are the properties of synthetic materials such as expanded polytetrafluorethylene. BC tubes, both straight and branched, were successfully developed. Cell cultures on the material showed that human smooth muscle cells could adhere to and proliferate on as well as migrate into the material while endothelial cells could form a confluent layer on the luminal side of the BC tubes. An in vivo evaluation of biocompatibility showed that bacterial cellulose is very well integrated into the host tissue and does not elicit any chronic inflammatory reactions. The biocompatibility of BC must be considered good, and the material therefore has the potential to be used as a scaffold for tissue engineered products. A toolbox was developed that allowed us to tailor the porosity and interconnectivity of the nanofibril network. The shape of the pores could also be altered. With such a toolbox, a scaffold of any shape on the nano scale can be constructed out of fibrils. This work contributes to the knowledge of relationships between the BC structure, its material properties and tissue interaction. Further in vivo evaluation is needed to determine the scaffolds’ and grafts’ biocompatibility. The future cell studies will show potential of microporous BC as a scaffold for TEBV but also other tissues and organ. It is our hope that this will result at a later stage in a product that can help the many patients in need. The development of functioning small diameter blood vessel substitute is awaited with keen interest by all patients with severe cardiovascular diseases.