Abstract
Up until June of 2016, there are roughly 120,000 people waiting for organ transplant in the United States. On average, less than 15% of patients on the organ transplant waiting list successfully receives a transplant surgery, indicating the serious shortage of organs for transplantation.[1] For patients that did receive a transplant, immunologic rejections remains a large challenge. Therefore, organ regeneration via tissue engineering is considered one promising alternative for patients in need. Contact guidance refers to cell alignment on the surface of biomaterials, and is induced by the topographic patterns and difference choices of materials. In soft tissue regeneration, the alignment of cells is critical toward preventing scar formation and promoting angiogenesis. In this work, laser patterned scaffolds are created on several biodegradable/biocompatible materials with precise width and depth to illicit cell responses. Two biodegradable polymers, poly(glycerol sebacate) (PGS), and poly(1,3-diamino-2-hydroxypropane-co-polyol sebacate)s (APS) with analogous mechanical properties to the soft tissues are synthesized and used in this work, along with polydimethylsiloxane (PDMS). In this study, fibroblasts were observed with good cell responses toward APS and PGS, with slight preference toward PGS, including cell morphology and proliferation rate, indicating its applicability in skin regeneration. For endothelial cells, good cell-material interactions were observed on both APS and PGS, with slight higher preference toward APS, indicating their potential applicability in vascular tissue engineering. Studies of cell responses toward laser ablated APS and PGS with 5-15μm gratings were conducted, and directional growth of fibroblasts were observed. The best patterns among tested of contact guidance of fibroblasts on microgrooved APS and PGS were observed with 7μm gratings, and 1.5 μm deep. Meanwhile, the high contact guidance of endothelial cells was observed on laser ablated APS and PGS with 5μm gratings and at 1.1μm depth. To achieve the ultimate goal of full organs regeneration through tissue engineering, biodegradable artificial microvascular tissues for transporting oxygen and nutrients play one of the most critical roles during regeneration. This study combined laser ablation technique with endothelial cell culture to create microfluidic devices of APS to mimic the in vitro microvasculature. Endothelial cell attachments were observed under flow-induced shear stress in physiological level in this microfluidic system. Through studies of contact guidance and cell seeding in microfluidic systems fabricated from laser ablation, it is believed that the combination of the two is the key to vasculature regeneration. Though there are much to be done still, this work has brought the idea of full organ regeneration one step closer to realization.