Engineering a Pro-Vasculogenic Capillary Network Regulating Host Responses

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Non-technical AbstractA key hurdle in regenerating tissues is the production of complex network of artificial blood vessels within the damaged areas, and the ability to cause host tissue to connect to these vessel networks. This process is necessary to ensure constant supply of oxygen and nutrient to growing cells and tissues in the areas. The PIs propose to develop an implantable scaffold containing artificial blood vessels, as well as appropriate biochemicals that can induce connections between the host tissue blood vessels and the engineered blood vessels. The success of this project will provide critical insights into how to influence and optimize this necessary integration between scaffold implants and host tissue, thereby accelerating regeneration of large tissues with severely damaged vessel networks. While conducting this project, research and education will be integrated through activities aligned with the efforts of the School for Science and Math at Vanderbilt U. The team will develop 1) grade-appropriate curriculum components that introduce high school students to engineering through a module on angiogenesis in biomaterial implants for tissue engineering and 2) a new graduate/upper level undergraduate course co-taught by the PI and CoPI on Tissue Engineering.Technical AbstractIn most natural tissues, blood capillaries lie within ~200 micrometers from each other to ensure a sufficient level of transport for oxygen, nutrients and waste products. Without this essential transport process through perfused vasculature, cells will die from ischemia, leading to necrotic regions. Thus, to engineer a successful tissue construct thicker than this diffusion-imposed limit, an artificial vascular network capable of supporting perfusion is required. Although continuous progress has been made, to date no research has demonstrated the integration of cell-laden microfluidic hydrogels with host vasculature in vivo. This critical step is necessary to fully exploit prevascularized constructs and enable the use of thick implantable cell-laden engineered tissues. Therefore, the PIs propose to engineer an immediately perfusable, implantable tissue construct that supports rapid angiogenesis and dramatically enhances anastomosis with host vasculature and host ingrowth by assembling hydrogels containing a high density capillary-like 3D microfluidic network; (ii) stem cells to promote vascularization and channel endothelialization; and (iii) short synthetic peptides to expedite host angiogenic response to further ensure timely vascularization/perfusion of the constructsThe results of this work will dramatically accelerate the application and translation of tissue engineering in the clinics.