Instructive Matrix Cues for Tissue Engineering Applications

Tissue engineering holds the promise of generating functional tissues to replace, or regenerate impaired native tissues by combining knowledge from cell biology, material science, and engineering. Designing instructive biomaterials that harness regeneration potential of native tissue requires incorporation of biochemical and biophysical cues. Besides, micro-tissues analogues are generated by emerging microfabrication techniques with precise control. This thesis aims to facilitate cell-matrix interactions by biochemical and topographical cues in collagen-based matrix for tissue regeneration in vivo with a focus on cardiac tissue engineering and wound healing applications, and creating cardiac micro-tissues with better physiological relevance in vitro. Chapter 2 introduces the key topics on designing instructive biomaterials for tissue engineering applications, with an emphasis on cardiac tissue engineering and wound healing applications. Chapter 3 describes covalent immobilization of peptides or angiogenic growth factors on collagen scaffolds. Immobilization efficiency and release profile were characterized and showed sustained releases. The modification did not affect the porous structure and tensile strength of the collagen scaffolds. Chapter 4 describes the study on protective effect of QHREDGS peptide on primary human keratinocytes and its efficacy in promoting diabetic wound healing. In vitro studies on normal and diabetic human keratinocytes showed that immobilized QHREDGS promoted keratinocyte attachment, collective migration, and survival against H2O2 stress. QHREDGS immobilized in chitosan-collagen hydrogel accelerated wound healing in diabetic mice by promoting re-epithelialization in vivo. Chapter 5 describes the design of a microfabricated bioreactor providing topographical cues to generate cardiac micro-tissues recapitulating native cardiac bundles. The micro-tissues were perfusable with micro-tubing in the center, mimicking capillaries. We demonstrated the utility of this platform by investigating the effects of nitric oxide on electrophysiological properties of the perfusable cardiac biowires. We finally conclude with remarks on the future prospects for biochemical and topographical cues in instructive biomaterials design for tissue engineering applications.Ph.D.2017-03-16 00:00:0