Human tissue undergoes constant change. Though such alterations are critical in combating disease, promoting healing, and allowing us to live happy, healthy lives, the specifics of how these changes affect cell behavior remain largely unknown. The proposed research seeks to address this knowledge deficiency through the development of biomaterials that can be modified reversibly and on demand with bioactive signaling proteins, thereby mimicking the dynamic biochemical properties of native tissue. These advanced materials will be used to study and direct stem cell function in response to changes in local signaling, providing new insight into disease/healing processes and a clear path towards the engineering of complex 3D tissues. Furthermore, a multidisciplinary education program involving new laboratory classes and research opportunities for students to learn the fundamentals of polymer chemistry, reaction engineering, and biomaterial science will be created. Open-source biomaterial-based modules will be developed in collaboration with local outreach programs that encourage under-represented groups to pursue careers in engineering. Modules will be made freely available online for others to use and help encourage a diverse community of future engineers with a passion for biomaterials. In partnership with the Society for Biomaterials, an inclusive support network will be built for young scientists, further ensuring their lifelong interest and a thriving future for the field of biomaterials.

Technical Abstract

Synthetic hydrogels have emerged as powerful in vitro cell culture platforms, providing simplified, near-physiological, 3D environments in which biological function can be directed in response to user-defined physicochemical signals. While gels have been exploited to control basic cell behaviors required to engineer simple homogenous tissues (e.g., adhesion, proliferation), strategies to govern more complex cellular processes (e.g., migration, differentiation) remain largely elusive. Even more difficult has been gaining the ability to direct such functions with spatiotemporal and dynamic control, required to create heterogeneous multicellular tissues. In the proposed research, this deficiency will be addressed by developing the first synthetic strategy to enable reversible patterning of 3D cell culture platforms with site-specifically-modified growth factors. These materials will be utilized to direct human mesenchymal stem cell differentiation within hydrogel matrices via the spatiotemporally patterned presentation of BMP-2 and TGF-beta. Operating at the interface of synthetic chemistry, protein engineering, and stem cell biology, student trainees will develop uniquely powerful biomaterials to probe and direct 4D cell fate in response to dynamic and heterogeneous microenvironmental signals. This research will be complemented by the creation of an open-source educational and outreach platform that inspires interest in engineering through biomaterial-centered programming.

National Science Foundation (NSF)
Division of Materials Research (DMR)
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Randy Duran
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University of Washington
United States
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