Non-technical: This NSF/DMR-BSF award by the Biomaterials Program in the Division of Materials Research to the University of Pennsylvania will be to advance our understanding of biomedical hydrogels for use in cartilage repair and regeneration. This award is cofounded by the Global Venture Funds in the Office of International Science and Engineering. Cartilage injuries account for nearly half a million surgical procedures performed each year, yet mounting evidence suggests that current interventions provide insufficient long-term benefits. Even as scientists uncover precisely how to regenerate cartilage tissue using mesenchymal stem cells, their routine clinical applications will still require a robust implantation process that retains the cells where desired and provides an environment that promotes repair. The overall goal of this project is to develop an injectable hydrogel that can be used for the encapsulation of mesenchymal stem cells and that can also withstand the mechanically demanding environment after placement in a joint. To accomplish these objectives, this research will be designing double-network hydrogels by incorporating two types of polymer networks that give rise to hydrogels that are tough and at same time support the encapsulation and differentiation of viable cells. The project will incorporate educational programs, and will involve students at various levels in the research activities. The scientific broader impact of the project is to both promote the progress of science through the design and investigation of novel hydrogels and at the same time to advance the national health by improving on our knowledge base of new treatments that can be used for biomedical applications in the future.
The overall goal of this project is to develop double-network hydrogels to encapsulate and control the chondrogenic differentiation of mesenchymal stem cells. Double-network (DN) hydrogels exhibit high strength and toughness, and mechanical features that may be desirable for application in cartilage defects and repair. However, at present there are no hydrogels that exist that are both injectable and bio-compatible. The specific aims of the project include: 1) synthesis of a series of double network hydrogels, and elucidate the structure-property relationships; and 2) assess mesenchymal stem cells survival and chondrogenesis within the double-network hydrogels. The proposed design involves the combination of covalently crosslinked hydrogels based on hyaluronic acid and poly(ethylene glycol) with fibrinogen to permit enzymatic degradability, as well as a self-assembled dynamic network based on biopolymers modified with guest-host groups that are dynamic and self-healing. This design incorporates the requisite rigid and ductile networks that are encompassed within DN hydrogels that are injectable based on the physical guest-host interactions and then covalently crosslinked through a photopolymerization reaction. The hydrogel properties will be tailored through alterations in the ratio and composition of each network with a focus on encapsulated mesenchymal stem cell viability and chondrogenesis as outcomes, in addition to desirable hydrogel mechanical properties. Upon successful completion, this work will identify fundamental understanding of hydrogel technology, as well as develop a potentially translational hydrogel for mesenchymal stem cells-based therapeutics for further investigations and biomedical applications.