Advances in the field of tissue engineering are increasingly reliant on biomaterials that instruct, rather than simply permit, a desired cellular response. Instructive biomaterials hold significant promise for clinical applications as well as to enable mechanistic studies in the laboratory. Given tissues are dynamic, spatially-patterned, and inhomogeneous over multiple length and time scales, my lab is developing new approaches to engineer biomaterials at the structural and biomolecular level to replicate these heterogeneities. These efforts are providing new insight regarding the degree of biomaterial complexity required to instruct cell behavior in the context of development, disease, and regeneration. I will describe a collagen biomaterial under development to address current barriers preventing regeneration of musculoskeletal tissues such as the osteotendinous (tendon-bone) junction and craniofacial bones. Here we use bioinspired design motifs to co-optimize bioactivity and mechanical competence in order to address translational and mechanistic challenges. I will subsequently describe a microfluidic forming technique to create libraries of optically-translucent hydrogels containing overlapping patterns of cell, matrix, and biomolecule cues. We are using this platform to explore the coordinated impact of structural, biomolecular, and metabolic cues on niche-mediated regulation of hematopoietic stem cell fate as well as malignant phenotype and therapeutic response in glioblastoma, the most common and lethal form of brain cancer. I will show how these platforms can be used as rheostats to regulate processes such as self-renewal vs. differentiation; regeneration and vascularization; as well as invasion and therapeutic resistance.
Brendan Harley is an Associate Professor in the Dept. of Chemical and Biomolecular Engineering at the University of Illinois at Urbana-Champaign. He received a B.S. in Engineering Sciences from Harvard University (2000), a Sc.D. in Mechanical Engineering from MIT (2006), and performed postdoctoral studies at the Joint Program for Transfusion Medicine at Children’s Hospital Boston. Over the last 10 years, his research group has focused on developing biomaterials that present biophysical and biomolecular signals to dynamically regulate cell behavior for applications in musculoskeletal regeneration, hematopoietic stem cell biomanufacturing, and models of invasive brain cancer. He has received funding from the NSF, NIH, American Cancer Society, the U.S. Army, and the AO Foundation. He received an NSF CAREER award in 2013, the 2014 Young Investigator Award from the Society for Biomaterials (USA), and was elected a Fellow of the American Association for the Advancement of Science in 2014. He also co-founded UK-based Orthomimetics, Ltd. (acquired by TiGenix, Ltd.), currently performing Phase I clinical trials on a material to repair osteochondral defects in the knee.
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