Challenges and Opportunities for Tissue Engineering
The architectural and functional reconstruction of skeletal defects are formidable challenges to modern medicine and surgery and it is of strategic importance for our community affected by unacceptably high levels of trauma and skeletal defects. The purification and molecular cloning of the bone morphogenetic and osteogenic proteins (BMPs/OPs) is helping to approach skeletal regeneration in molecular terms. A critical question is whether the presence of multiple forms of BMPs has a biological and therapeutic significance. The BRL research plan focuses on optimal molecular combinations, developing a structure-activity profile amongst the members of the BMP/OP superfamily. In addition, several key questions need to be addressed. Predictable therapeutic osteogenesis will require information concerning the expression and cross regulation of members of the BMP/OP and TGF-beta families during tissue morphogenesis, as well as receptor expression after ligands implantation. The selection of the carrier substrata for local delivery of BMPs/OPs is of paramount importance for future applications, since it is the composite of a carrier substratum together with BMPs/OPs that triggers the bone induction cascade. Thus, a pivotal issue to engineer tissue morphogenesis and regeneration is the development of ?smart? biomaterials with specific surface and geometric characteristics capable of spontaneously initiating bone morphogenesis, ie, substrata with intrinsic osteoinductive activity. The incorporation of specific biological activities into biomaterials achieved by manipulating the geometry of the substratum will help to engineer morphogenetic responses which will ultimately result in predictable regeneration for the treatment of human bone defects. By using immunolocalization, in situ hybridization, northern analysis, protein chemistry, specialized histological processing and undecalcified histology, elemental analysis and primate animal modelling, our research plan is focused on tissue morphogenesis and regeneration of multiple organs and tissues including cartilage, bone and periodontium, and uses both local and systemic administration strategies of BMPs/OPs and other morphogens for local tissue morphogenesis and restoration of systemic bone mass in clinical contexts. Finally, the broad multi-faceted intellectual and technological expertise of the BRL is available for capacity development of staff and students, and to develop a culture of research and scientific discipline for a modern and globally educated South Africa.