Implantation and characterization of tissue engineered microvascular grafts

Abstract

The socioeconomic constraints generated by patients with cardiovascular disease necessitates the development of novel treatment strategies for the pathologies associated with disease progression. One promising field of active research and development is Cardiovascular Tissue Engineering. It is believed this discipline will ultimately provide alternative strategies for the development of vascular bypass conduit, bioprosthetic valves, functional microvascular networks, and solid organ replacement tissue. The primary goal of this project was to test the hypothesis that, following implantation, tissue engineered microvascular grafts are capable of inosculation with host coronary vasculature and attenuating the loss of ventricular function following acute myocardial infarction. To test this hypothesis, microvascular grafts were constructed of adipose-derived microvascular fragments suspended in a 3-dimensional matrix. These tissue engineered grafts were transplanted and evaluated in a number of in vivo research scenarios. Research protocols were designed to critically evaluate the potential of microvascular network grafting in multiple tissue sites, and in differing pathophysiologic conditions. Microvascular grafts were initially implanted and studied in a subcutaneous position in recipient animals. Following implantation, the microvessel network within the grafted construct established spontaneous anastomotic connections with the host. Inosculation of the grafted microvessles and host circulation occurred rapidly following surgical placement, with evidence of significant vascular remodeling within the graft. The experimental grafts were also evaluated in the cardiac position following acute cardiac injury. Perfusion was realized through the grafted microvascular tissue. The resulting microvasculature was complete with well-formed arterioles, venules, and capillaries. It was established that development of left ventricular dysfunction following experimental coronary artery occlusion was abated in animals treated with epicardial placement of microvascular grafts. Interestingly, while there was overwhelming evidence of microvascular remodeling in both the subcutaneous and cardiac position, there was a noted tissue-specific adaptation that occurred. Grafts in the cardiac position had a higher vascular density than those in the subcutaneous position, and developed a vessel-type distribution that was approximate to that observed in native epicardium. The results described in this dissertation project support the utility of tissue engineered microvascular grafts for the treatment of pathophysiologic tissue within the cardiovascular system proper, as well as in peripheral systems.