Microfabricated Poly (ethylene glycol) Based Hydrogels for Microvascular Tissue Engineering Applications
Cuchiara, Michael Paul
West, Jennifer L.
Doctor of Philosophy
Shortages in donor organs and the lack of therapeutic treatment options to address tissue loss and end-organ failure has led to intense research into tissue engineering based therapeutics. Cellular, tissue, and organ level therapeutics hold the potential to shift clinical paradigms and drastically improve healthcare outcomes. However, to date the only successful tissue engineering therapeutics have been limited to thin and avascular tissues such as skin, cartilage and the bladder. This is primarily due to the absence of a perfusable vasculature to transport nutrients and waste during in vitro tissue development and inadequate host-implant vascular integration upon implantation. In this thesis we set out to develop hydrogel microfabrication technologies to (1) improve in vitro mass transport, (2) integrate self-assembling microvascular networks with microfabricated channels and (3) incorporate and support functional parenchymal cellular elements within in vitro constructs. Application of microfabrication technologies to PEG hydrogels requires that fabrication schemes are cell compatible, robust for handling and imaging and most importantly allow for precise micron level control of both fluid perfusion and hydrogel structure fabrication. Herein we report multiple cell compatible 1 microfabrication schemes that employ multilayer replica molding and photolithographic hydrogel fabrication techniques. Systems designed with these techniques resulted in improved in vitro mass transport, integration of selfassembled microvascular networks with fabricated structures and the ability to pattern multilayer heterogeneous hydrogel structures that contain and support multiple cellular elements. The progress reported herein has broad applicability towards the development of biomaterials with highly biomimetic structural-functional characteristics. More specifically these hydrogel microfabrication technologies hold the promise to improve the therapeutic potential of tissue engineered constructs and provide more biologically applicable pre-clinical tissue models. 2
Engineering; Biomedical engineering