Bioengineering Seminar Series: Sarah Heilshorn

Friday, February 28, 2014
9:00 a.m.-10:00 a.m.
Pepco Room (1105), Jeong H. Kim Engineering Building
Professor Ian White
ianwhite@umd.edu

Designing Injectable Biomaterials for Stem Cell Transplantation

Sarah Heilshorn
Assistant Professor
Department of Materials Science and Engineering
Stanford University

Stem cell transplantation is a promising therapy for a myriad of debilitating diseases and injuries; however, current delivery protocols are inadequate. Transplantation by direct injection, which is clinically preferred for its minimal invasiveness, commonly results in less than 5% cell viability, greatly inhibiting clinical outcomes. We demonstrate that mechanical membrane disruption results in significant acute loss of viability at clinically relevant injection rates. As a strategy to protect cells from these damaging forces, we show that cell encapsulation within hydrogels of specific mechanical properties will significantly improve viability. Building on these fundamental studies, we have designed a reproducible, bio-resorbable, customizable hydrogel using protein-engineering technology. In our Mixing-Induced Two-Component Hydrogel (MITCH), network assembly is driven by specific and stoichiometric peptide-peptide binding interactions. By integrating protein science methodologies with simple polymer physics models, we manipulate the polypeptide chain interactions and demonstrate the direct ability to tune the network crosslinking density, sol-gel phase behavior, and gel mechanics. This is in contrast to many other physical hydrogels, where predictable tuning of bulk mechanics from the molecular level remains elusive due to the reliance on non-specific and non-stoichiometric chain interactions for network formation. Our MITCH materials enable stem cell and growth factor encapsulation at constant physiological conditions – a significant advantage over other commonly used hydrogels such as collagen and Matrigel. Furthermore, the hydrogel network can be easily modified to deliver a variety of other bioactive payloads such as growth factors, peptide drugs, and hydroxyapatite nanoparticles. Through a series of in vitro and in vivo studies, we demonstrate that these materials may significantly improve transplanted stem cell retention. Specific applications under investigation include co-delivery of induced pluripotent stem cell-derived endothelial cells with vascular endothelial growth factor to achieve blood vessel regeneration and the co-delivery of adipose-derived stromal cells with hydroxyapatite nanoparticles to promote bone tissue regeneration.


Audience: Graduate  Faculty  Post-Docs 

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