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Jason A. Burdick, an associate professor in Bioengineering at the University of Pennsylvania, will present a lecture on "Dynamic Biomaterials to Modulate Stem Cell Behavior and Tissue Interactions" as part of the Wallace H. Coulter Department of Biomedical Engineering's Young Innovators in Biomedical Engineering Seminar.
Abstract:
Stem cells (e.g., mesenchymal stem cells [MSCs]) respond to many cues from their microenvironment, which may include chemical signals, mechanics and topography. These cues may be incorporated into scaffolding to control stem cell differentiation and optimize their ability to produce tissues in regenerative medicine. Despite the significant amount of work in this area, the materials have been primarily static and uniform. To this end, we have developed a sequential crosslinking process that relies on our ability to crosslink functional biopolymers (e.g., methacrylated hyaluronic acid [HA]) in two steps, namely a Michael-type addition reaction to partially consume reactive groups and then a light-initiated free-radical polymerization to further crosslink the material. With light exposure during the second step comes control over the material in space (via masks and lasers) and time (via intermittent light exposure). We are applying this technique for numerous applications. For example, when the HA hydrogels are crosslinked with MMP degradable peptides with thiol termini during the first step, a material that can be degraded by cells is obtained. However, cell-mediated degradation is obstructed with the introduction of kinetic chains during the second step, leading to spatially controlled cell degradability. Due to the influence of cellular spreading on MSC differentiation, we have controlled cell fates by controlling their spread ability, for instance toward osteoblasts in spread areas and adipocytes when cell remained rounded. We are also using the process of stiffening with time to investigate mechanically induced differentiation, particularly in materials with evolving mechanics. Toward applications in cardiac repair, we are applying HA hydrogels as injectable materials that can reduce stresses in the heart wall after infarction. Our ability to design materials with controlled properties and degradation is allowing us to investigate the influence of these properties on the tissue response and functional outcomes in a clinically relevant ovine model of infarction. Overall, these advanced HA hydrogels provide us the opportunity to investigate diverse and controlled material properties for a range of biomedical applications.
Dr. Burdick is being hosted by Johnna Temenoff, Ph.D., Assistant Professor, Coulter Department.