Mesenchymal stem cell differentiation on biomimetic surfaces for orthopaedic applications

Abstract

A large number of people require surgery, including total joint replacements, to treat bone and joint degenerative and inflammatory diseases. Implant-related infections and failure of an implant to osseointegrate with the bone tissue are common causes of implant failure. Despite efforts to avoid initial bacterial adhesion on an implant surface, nosocomial infections do occur. Hence, it is crucial to have the means to down-modulate the deleterious effects of bacterial endotoxins like lipopolysaccharide (LPS) on differentiating osteoblasts on the implant surface while treatment for the infection is given. Implant failure is also partly attributed to the poor vascularization around the healing bone. Thus, in the present thesis, the aims are to develop an anti-bacterial, osteogenic substrate for bone cell differentiation, and to develop an angiogenic substrate to promote endothelial cell differentiation, as an adjunct to osteogenesis. To address the concern of opportunistic bacterial infections at the bone-implant interface, a study is also done to evaluate the effects of a bioactive lysophospholipid on differentiating osteoblasts growing on the osteogenic substrate in the presence of a selected bacterial endotoxin. Taken together, the work in the present thesis forms the basis for future work to be done in order to take the functionalized substrates closer to clinical applications.