Silk-Based Platforms for Engineering the Microvascular Niche and Vascularizing Tissue Constructs

A major challenge in the tissue engineering field is the inability to recreate the microvasculature within engineered tissue equivalents. The microvasculature plays an important role in mediating tissue homeostasis and is therefore a critical component for engineering functional tissues for both regenerative medicine and in vitro tissue modeling purposes. The challenge of engineering the microvasculature stems from the inherent small scale and complexity of its cellular and extracellular components. Lining the microvasculature are endothelial cells anchored to a thin layer of extracellular matrix referred to as the basement membrane. Surrounding the basement membrane are perivascular cells. These cellular and extracellular components create a barrier between the vascular space and the tissue space that regulates molecular transport and cell migration between the blood and surrounding tissue. Despite the challenges of engineering the microvasculature, many promising technologies have been developed, however they remain limited in terms of clinical relevance and feasibility. To address these limitations, the goal of this thesis was to use silk protein to develop tunable scaffold platforms that support the microvascular niche and promote vascularization of large tissue constructs. In this thesis, the development and characterization of silk-based scaffold platforms for recapitulating various aspects of the microvasculature is pursued. A basement membrane model is developed using a porous silk film and investigated for supporting in vitro platelet production. A silk-based microfluidic device is also developed, which is patterned with a network of channels that mimics microvascular hierarchy. Finally, a porous silk scaffold containing an array of hollow channels is developed that exhibits enhanced oxygen and nutrient delivery for supporting large tissue formation. Overall, these scaffold platforms satisfy an unmet need in the field for tools that enable engineering of tissues that contain a microvasculature component. The broader impact of the silk-based scaffold platforms developed in this thesis provide important tools for engineering the microvasculature that will enable construction of advanced tissue constructs for in vitro modeling and regenerative medicine purposes.