Protein Engineering of Multi-functional Biomaterials for Regenerative Medicine
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 damage results in significant acute loss of viability at clinically relevant injection rates. As a strategy to protect cells from these detrimental forces, we show that cell encapsulation within hydrogels can significantly improve transplanted cell viability. Building on these fundamental studies, we have designed a family of injectable, bioresorbable, customizable hydrogels using protein-engineering technology. By integrating protein science methodologies with simple polymer physics models, we manipulate the polypeptide chain interactions and demonstrate the direct ability to tune the material properties including hydrogel mechanics, cell-adhesion, and biodegradation. Through a series of in vitro and in vivo studies, we demonstrate that protein-engineered hydrogels may significantly improve transplanted stem cell retention and regenerative function. Furthermore, many of the lessons learned about designing injectable biomaterials can be extended to design new bio-inks for 3D printing applications. While 3D printing has enormous potential for tissue engineering, few bio-inks are currently available to facilitate the printing of complex, cell-laden constructs. We demonstrate the design of a new, customizable bio-ink that enables the printing of multiple cell types into distinct geometric forms.