Tissue engineering has great potential in extending the quality and extent of patient life, as well as significantly reducing the cost of health care by providing tissue engineered constructs (TECs) for replacement of diseased, non-functioning, or missing tissues. At UTMDACC, tissue engineering is being applied to develop new reconstructive surgery modalities for repair or replacement of tissue defects attributed to tumor resection, congenital anomalies, and trauma. Despite advances in clinical outcomes with conventional tissue transfer clinicians are still limited by suboptimal results and morbidity associated with harvest of autologous tissue. TECs based on autologous cells grown ex vivo from a biopsy have the potential to markedly reduce the current limitations. However, TECs to date are not clinically translatable due to the predominant design constraint of lacking the ability to vascularize the TEC after grafting/transplanting to a recipient site at a rate sufficient enough to support parenchymal cell survival. While vascularization of TECs clearly contributes to TEC survival and clinical translation, the exact modalities and underlying biological mechanisms that provide vascularization remain poorly addressed. This research proposal is based on the following two concepts: TECs are a sophisticated and selective form of tissue grafting, and microvascular endothelial cells (MECs) control tissue mass in vivo. The broad, long-term objectives of this New Investigator proposal are to elucidate the general mechanism of TEC-recipient inosculation and to examine how CD144, a MEC-MEC intercellular adhesion molecule, affects this inosculation. Both an in vivo rat model and microcarrier based in vitro model are coupled with 2D/3D fluorescence microscopy, specific MoAbs, and hypoxic conditions to address the following aims: (a) What role does TEC-recipient inosculation play in TEC vascularization? (b) What are the biological functions of CD144, principally with regards to its role in inosculation and its regulation by the unique TEC microenvironment?
