Protein engineered biomaterials for muscle tissue engineering applications
- Abstract There is a tremendous need for muscle regeneration therapies to replace tissue that is lost due to disease or injury. This work is focused on developing engineered replacement therapies for lost or damaged skeletal and cardiovascular muscle tissue. In order to create viable, clinically relevant regenerative therapies, I have used recombinant protein technology to synthesize a family of protein-engineered biomaterials that incorporate critical cues for the recapitulation of in vivo muscle tissue conditions. Crucially, these biomaterials allow the independent tuning of multiple biomaterial properties including cell adhesivity, biomaterial stiffness, and topographical cues. Each of these biomaterial properties impacts muscle cell behavior independently as well as in concert. I have exploited the range of biomaterial tunability available to us to identify biomaterial conditions that enable production of striated muscle tissue using primary human skeletal muscle myoblasts (hMBs) that may be electrically paced. I have further demonstrated that mouse model skeletal muscle cell lines do not accurately recapitulate primary human myoblast behavior in response to biomaterial properties, particularly with respect to integrin-matrix interactions. Importantly, the expression of mature muscle markers that indicate muscle cell differentiation could be accelerated simply by changing biomaterial stiffness and introducing biomaterial microtopography. Finally, as demonstration that this protein-engineered biomaterial strategy may have application in the regeneration of myocardial as well as skeletal muscle tissue, cardiomyocytes derived from human embryonic stem cells exhibited good cell viability and improved contractility on these biomaterials. This thesis represents important advancements in the development of regenerative muscle tissue engineered constructs.
|Type of resource
|electronic; electronic resource; remote
|1 online resource.
|Stanford University, Department of Chemistry
|Khosla, Chaitan, 1964-
|Khosla, Chaitan, 1964-
|Statement of responsibility
|Submitted to the Department of Chemistry.
|Thesis (Ph.D.)--Stanford University, 2012.
- © 2012 by Debanti Sengupta
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