The extracellular matrix (ECM) is a complex organization of structural proteins such as collagens and proteoglycans. Understanding that the ECM is dynamic and often spatially patterned or heterogeneous over the length-scale of traditional biomaterials, we are developing instructive biomaterials that present microenvironmental cues in spatially and temporally defined manners. I will describe development of a collagen biomaterial to address critical barriers preventing regeneration of orthopedic insertions such as the osteotendinous (tendon-bone) junction. Here, replicating spatial gradients in mineral content and matrix anisotropy across a single biomaterial construct enables us to drive mesenchymal stem cell (MSC) differentiation down osteotendinous lineages in a spatially-selective manner. Further, we have created bioinspired core-shell structures (e.g., porcupine quills) in order to balance bioactivity and mechanical competence concerns. 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 'tissue biochip' platform to dissect the coordinated impact of spatially-organized cell and matrix signals on (1) niche-mediated regulation of hematopoietic stem cell fate; and (2) the malignancy and therapeutic response of human glioblastoma multiforme cells. I will show how these biomaterial platforms can be used as rheostats to regulate critical cellular processes such as stem cell self-renewal vs. differentiation; tissue regeneration and vascularization; and the etiology and malignancy of cancer.
Brendan Harley received a B.S. in Engineering Sciences from Harvard University (2000) and a Sc.D. in Mechanical Engineering from MIT (2006). He was a post-doctoral fellow in the Joint Program for Transfusion Medicine at Children's Hospital Boston and Harvard Medical School (2006 -- 2008). In 2008 he joined the faculty at the University of Illinois at Urbana-Champaign where he is an Assistant Professor in Chemical and Biomolecular Engineering and directs the Engineered Cellular Microenvironments and Microstructures Laboratory. He is the co-founder of UK-based Orthomimetics, Ltd. (now TiGenix, Ltd.), currently performing Phase I clinical trials on a biomaterial for osteochondral repair. He has received funding from the NSF, NIH, American Cancer Society, and the AO Foundation. He has co-authored the book 'Cellular materials in nature and medicine' (Cambridge University Press, 2010). He is a 2013 recipient of a NSF CAREER award and the 2014 Society for Biomaterials Young Investigator Award.
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