Bio-Inspired Tissue Engineering Design for Vascular Regenerative Therapy
Tissue engineering aims to understand the naturally-occurring, complexly efficient biological systems that control our development, repair, aging, and death in order to improve current diagnostics, therapies, as well as prevention strategies. By elucidating which system components [i.e. cells, extracellular matrix (ECM) proteins, growth factors, genes, transcription factors, etc., or a combination of these] are responsible for which biological activities, superiorly efficient strategies for tissue regeneration can be developed. Thus, natural tissue properties, such as scale, structure, and organization provide the best inspiration for scaffold designs essential to many tissue engineering endeavors. Electrospinning technology has immense potential in providing these endeavors with the means to materialize such designs, especially the development of vascular regenerative therapy. Through its implementation, electrospinning can utilize polymers to produce ECM-mimicking fibers and organize them into scaffolds that provide cells with a familiar environment, which may result in desired cellular activity. Biological polymers would be the ideal electrospun component, but often lose much of its mechanical integrity when isolated from its natural environment. Biodegradable, biocompatible synthetic polymers offer a promising alternative, as they can support cellular activity, are mechanically tunable, and can easily be made bioactive via immobilization of growth factors, ECM proteins, and other substances that may accelerate ultimate tissue regeneration. In this dissertation, we attempt to address the unmet need for a suitable small-diameter vascular graft by specifically investigating the potential of bio-inspired design aspects in accomplishing vascular repair and regeneration. Here, we pay particular attention to micro-/nano-structure, topography, and chemical surface modification and their role in mechanical compliance, thrombosis inhibition, vascular re-endothelialization, and vascular regeneration potential. We detail the electrospinning of a novel bilayered, micro-/nanofibrous vascular graft scaffold that minimizes mechanical compliance mismatch with native vessels. We then demonstrate that the protective epithelial glycoprotein, mucin, may be used to inhibit thrombosis on synthetic vascular grafts. Finally, we illustrate that topographical customization can enhance endothelialization of and cell infiltration into synthetic vascular graft scaffolds. Taken together, we offer design suggestions that may significantly aid the quest taken on by vascular tissue engineering to find the ideal vascular graft.