Dynamic and Reversible Control over Biological Signals in Hydrogel Matrices

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Nontechnical:This award by the Biomaterials program in the Division of Materials Research to the University of Colorado at Boulder is cofunded by the Biotechnology, Biochemical, and Biomass Engineering program in the Division of Chemical, Bioengineering, Environmental, and Transport Systems (ENG). This award supports the study of adult stem cell for the potential treatment of injured or diseased tissues. While these cell-based therapies provide a possible avenue to restore function and improve quality of life, current limitations in their translation include the inability to control the differentiation of the stem cells, low survival of the transplanted cells, etc. Biomaterial systems that provide the right signals to these cells could help overcome many of these problems. To address this significant need, this project will develop advanced biomaterial systems for the culture of bone-marrow derived stem cells, and the materials and methods will allow us to better understand which signals are important and how they should be presented to the cells. We expect that this research will translate into new biomaterial systems for the delivery of adult stem cells that will improve their safety and efficacy. During this research, graduate students will be trained in state-of-the-art methods at the interface of biology with engineering, and prepared for scientific careers in areas of national need (e.g., biomaterials, medical devices, and drug delivery). The team will also integrate undergraduate students and high school students as part of a sustained effort to communicate this work to the local public through outreach programs. In addition to publication of results that will be broadly accessible, we will also continue to develop hands-on demonstrations for visiting secondary students, teachers and parents, as the visual aspects of imaging cells in 3D captures the attention and excitement of many prospective future scientists and engineers.Technical:This award supports the development of hydrogel biomaterials for the culture of human mesenchymal stem cells (hMSCs). hMSCs are adult stem cells that are being used in numerous clinical trials to promote healing of injured or diseased tissues. With this award, hydrogel scaffolds will be synthesized and characterized that allow one to introduce important biological signals at the interface of the biomaterial matrix with the hMSCs. The approach exploits a thiol-ene reaction mechanism and particularly an allyl-sulfide functionality. Many thiol-containing biomacromolecules (e.g., proteins, peptides) can be conjugated to the ally-sulfide moieity through reversible exchange reactions, which allow user-controlled modification of the scaffold biochemical functionality. Since the expansion and controlled differentiation of hMSCs often involves sequential presentation of biological signals, the materials developed as part of this award will allow us to study and engineer systems for improved culture of hMSCs, as well as design improved hMSC delivery vehicles for therapeutic applications. As part of this research, students at multiple levels (high school, undergraduate and graduate) will be trained in polymer and peptide synthesis, bioconjugation techniques, hydrogel characterization, stem cell culture and advanced light microscopy methods. The knowledge learned from this research will be integrated into course content in advanced Biomaterials and Tissue Engineering courses, as well as communicated to the general public through numerous outreach programs at the University of Colorado.