Brendan A Harley

Brendan A Harley
Brendan A Harley he/him/his
  • Robert W. Schaefer Professor
(217) 244-7112
110 Roger Adams Laboratory

Pursues the fabrication, characterization, and testing of biomaterials for in vivo and in vitro tissue engineering applications.

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Biography

Brendan Harley is currently a Professor in Chemical and Biomolecular Engineering and a research theme leader in the Carl R. Woese Institute for Genomic Biology at the University of Illinois at Urbana-Champaign. Dr. Harley develops biomaterials that replicate the dynamic, spatially-patterned, and heterogeneous microenvironment found in the tissues and organs of our body. He and members of his lab use this approach to generate new insight regarding how biomaterial cues can instruct cell responses in the context of development, disease, and regeneration. Harley co-authored the book ‘Cellular materials in nature and medicine’ (Cambridge University Press, 2010) along with more than 100 peer-reviewed manuscripts. Harley has received funding from the NSF, NIH, American Cancer Society, the U.S. Army, and the AO Foundation. He recognized as a 2013 recipient of a NSF CAREER award, the 2014 Young Investigator Award from the Society for Biomaterials, and was elected a Fellow of the American Association for the Advancement of Science (2014). He 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. Professor Harley joined the department in 2008. He received his SB from Harvard University in 2000 and SM/ScD from MIT in 2002 and 2006. His post-doctoral studies were completed at the Joint Program in Transfusion Medicine at Boston Children’s Hospital.

Education

  • Research Fellow, Joint Program in Transfusion Medicine, Children's Hospital Boston, 2006-2008
  • Sc.D., Massachusetts Institute of Technology, 2006
  • S.M., Massachusetts Institute of Technology, 2002
  • S.B., Harvard University, 2000

Journal Editorships

  • Associate Editor, Science Advances.
  • Editorial Board, Tissue Engineering.

Research Interests

  • Extracellular Matrix Analogs, Cell and Tissue Engineering

Research Statement

Scientists, engineers, and physicians have for decades worked to better understand the onset and progression of disease, prevent further damage after injury, and develop approaches to enhance healing. A critical bottleneck in these efforts is the complexity that arises from the non-uniform properties of the tissues and organs of our bodies. The tissue microenvironment can vary in time – such as during development or with chronic disease – or in space – such as gradients in cell and matrix content found across tumors and musculoskeletal tissue insertional zones.

Such heterogeneities have inspired me to develop approaches to create unique biomaterials that are dynamic, spatially-patterned, and inhomogeneous over multiple length and time scales. To do this my lab is engineering biomaterials at the structural, mechanical, and biomolecular level. We have demonstrated: (1) multi-scale and bio-inspired composite design strategies to balance functional and biomechanical concerns; (2) techniques to create spatially-graded and overlapping patterns of cells, matrix, and biomolecules across biomaterials for regenerative repair of orthopedic insertions and to mimic the tumor microenvironment; (3) biomaterials to regulate temporal processes such as transient growth factor sequestration or the balance of paracrine vs. autocrine signals in an artificial stem cell niche.

These biomaterials provide unique tools to explore the impact of the tissue environment on the behavior of cells in the context of development, disease, and regeneration. They offer promise as materials to be implanted into the body to speed recovery after injury.

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Books Authored or Co-Authored (Original Editions)

  • L.J. Gibson, M.F. Ashby, B.A. Harley, "Cellular Materials in Nature and in Medicine," Cambridge University Press, (2010).

Books Edited or Co-Edited (Original Editions)

  • A. J. Wagoner Johnson and B.A.C. Harley (eds.), "Mechanobiology of Cell-Cell and Cell-Matrix Interactions," Springer, (2011).

Chapters in Books

  • B.A. Harley and I.V. Yannas in J.G. Webster (ed.), "Skin: Tissue Engineering for Regeneration," in The Encyclopedia of Medical Devices and Instrumentation, 2nd Edition, New York: Wiley (2006).
  • B.A. Harley and I.V Yannas, "In vivo synthesis of tissues and organs," in Principles of Tissue Engineering, R. Lanza, R. Langer, and J.P. Vacanti (eds.), 3rd Edition, New York: Elsevier (2007).
  • S.R. Caliari and B.A. Harley, "Collagen-GAG Materials," in P. Ducheyne (ed.) Comprehensive Biomaterials, Kidlington (UK): Elsevier, (2011).
  • D.W. Weisgerber, S.R. Caliari, B.A.C. Harley, "Synthesis of layered, graded bioscaffolds," in Structural interfaces and attachments in biology, S. Thomopoulos, G. Genin, V. Birman (eds.), Springer, 2012.
  • B.A.C. Harley and I.V Yannas, ‘In Vivo Synthesis of Tissues and Organs,’ in Principles of Tissue Engineering, R. Lanza, R. Langer, and J.P. Vacanti (eds.), 4rd Edition, New York: Elsevier, 2013.

Selected Articles in Journals

  • M.T. Ngo, B.A.C. Harley, ‘Perivascular signals alter global gene expression profile of glioblastoma and response to temozolomide in a gelatin hydrogel,’ Biomaterials, 2018. DOI: 10.1016/j.biomaterials.2018.06.013.
  • D.W. Weisgerber, D.J. Milner, H. Lopez-Lake, M. Rubessa, S. Lotti, K. Polkoff, R.A. Hortensius, C.L. Flanagan, S.J. Hollister, M.B. Wheeler, B.A.C. Harley, ‘A mineralized collagen-polycaprolactone composite promotes healing of a porcine mandibular ramus defect,’ Tissue Eng Part A, 24(11-12): 943-54, 2018.
  • J.C. Pence, K.B.H. Clancy, B.A.C. Harley, ‘Pro-angiogenic activity of endometrial epithelial and stromal cells in response to estradiol in gelatin hydrogels,’ Adv. Biosys., 1(9):1700056, 2017.
  • S. Pedron, J.S. Hanselman, M. Schroeder, J.N. Sarkaria, B.A.C. Harley, ‘Extracellular hyaluronic acid influences the efficacy of EGFR tyrosine kinase inhibitors in a biomaterial model of glioblastoma,’ Adv. Healthc. Mater., 6(21):1700529, 2017.
  • M.T. Ngo, B.A.C. Harley, ‘The influence of hyaluronic acid and glioblastoma cell co-culture on the formation of endothelial cell networks in gelatin hydrogels,’ Adv. Healthc. Mater., 6(22):1700687, 2017.
  • W.K. Grier, A.S. Moy, B.A.C. Harley, ‘Cyclic tensile strain enhances human mesenchymal stem cell Smad2/3 activation and tenogenic differentiation in anisotropic collagen-glycosaminoglycan scaffolds,’ Eur. Cell Mater., 33:227-39, 2017.
  • J.-S. Choi, B.A.C. Harley, ‘Marrow-inspired matrix cues rapidly affect early fate decisions of hematopoietic stem and progenitor cells,’ Sci. Adv., 3(1):e1600455, 2017.
  • B.P. Mahadik, N.A.K. Bharadwaj, R.H. Ewoldt, B.A.C. Harley, ‘Regulating dynamic signaling between hematopoietic stem cells and niche cells via a hydrogel matrix,’ Biomaterials, 125:54-64, 2017.
  • L.C. Mozdzen, A. Vucetic, B.A.C. Harley, ‘Modifying the strength and strain concentration profile within collagen scaffolds using customizable arrays of poly-lactic acid fibers,’ J. Mech. Behav. Biomed. Mater., 66:28-36, 2017.
  • X. Ren, V. Tu, D. Bischoff, D.W. Weisgerber, M.S. Lewis, D.T. Yamaguchi, T.A. Miller, B.A.C. Harley, J.C. Lee, ‘Nanoparticulate mineralized collagen scaffolds induce in vivo bone regeneration independent of progenitor cell loading or exogenous growth factor stimulation,’ Biomaterials, 89:67-78, 2016.
  • Z. Rahil*, S. Pedron*, X. Wang, T. Ha, B.A.C. Harley§, D.E. Leckband§, ‘Nanoscale mechanics guides cellular decision making,’ Integr. Biol. (Camb), 8(9):929-35, 2016. * co-first authors. § co-corresponding authors.
  • B.P. Mahadik, S. Pedron Haba, L.J. Skertich, B.A.C. Harley, ‘The use of covalently immobilized stem cell factor to selectively affect hematopoietic stem cell activity within a gelatin hydrogel,’ Biomaterials, 67:297-307, 2015.
  • X. Ren, D. Bischoff, D.W. Weisgerber, M.S. Lewis, V. Tu, D.T. Yamaguchi, T.A. Miller, B.A.C. Harley, J.C. Lee, Osteogenesis on nanoparticulate mineralized collagen scaffolds via autogenous activation of the canonical BMP receptor signaling pathway, Biomaterials, 2015.
  • S.R. Caliari, W.K. Grier, D.W. Weisgerber, Z. Mahmassani, M.D. Boppart, B.A.C. Harley, Collagen scaffolds incorporating coincident patterns of instructive structural and biochemical cues for osteotendinous junction engineering, Adv. Healthc. Mater., 2015.
  • S. Pedron, E. Becka, B.A.C. Harley, Spatially-gradated hydrogel platform as a three-dimensional engineered tumor microenvironment, Adv. Mater., 27(9):1567-72, 2015.
  • S.R. Caliari, E.A. Gonnerman, W.K. Grier, D.W. Weisgerber, J.M. Banks, A.T. Alsop, J.-S. Lee, R.C. Bailey, B.A.C. Harley, Collagen scaffold arrays for combinatorial screening of biophysical and biochemical regulators of cell behavior, Adv. Healthc. Mater., 4(1):58-64, 2015.
  • S.R. Caliari, B.A.C. Harley, Structural and biochemical modification of a collagen scaffold to selectively enhance MSC tenogenic, chondrogenic, and osteogenic differentiation, Adv. Healthc. Mater., 3(7):1086-96, 2014.
  • S.R. Caliari, L.C. Mozdzen, O.E. Armitage, M.L. Oyen, B.A.C. Harley, Periodically-perforated core-shell collagen biomaterials balance cell infiltration, bioactivity, and mechanical properties, J. Biomed. Mater. Res. Pt. A, 102(4):917-27, 2014.
  • B.P. Mahadik, T.D. Wheeler, L.J. Skertich, P.J.A. Kenis, B.A.C. Harley, Microfluidic generation of gradient hydrogels to modulate hematopoietic stem cell culture environment, Adv. Healthc. Mater., 3(3):449-458, 2014.
  • R.A. Hortensius, B.A.C. Harley, The use of bioinspired alterations in the glycosaminoglycan content of collagen-GAG scaffolds to regulate cell activity, Biomaterials, 34(31):7645-52, 201
  • S. Pedron, E. Becka, B.A.C. Harley, Regulation of glioma cell phenotype in 3D matrices by hyaluronic acid, Biomaterials, 34(30):7408–17, 2013.
  • C. Nombela-Arrieta, G. Pivarnik, B. Winkel, K.J. Canty, B.A.C. Harley, J.E. Mahoney, J. Lu, A. Protopopov, L.E. Silberstein, Quantitative imaging of hematopoietic stem and progenitor cell localization and hypoxic status in the bone marrow microenvironment, Nat. Cell Biol., 15(5):533-543, 2013.
  • J.S. Choi, B.A. Harley, The combined influence of substrate elasticity and ligand density on the viability and biophysical properties of hematopoietic stem and progenitor cells, Biomaterials, 33(18):4460-4468, 2012.
  • S.R. Caliari, B.A.C. Harley, The effect of anisotropic collagen-GAG scaffolds and growth factor supplementation on tendon cell recruitment, alignment, and metabolic activity, Biomaterials, 32(23):5330-40, 2011.
  • T. Martin, S.R. Caliari, P. Williford, B.A. Harley*, R.C. Bailey*, The generation of biomolecular patterns in highly porous collagen-GAG scaffolds using direct photolithography, Biomaterials, 32(16):3949-57, 2011. *Co-corresponding authors
  • B.A. Harley, A.K. Lynn, Z. Wissner-Gross, W. Bonfield, I.V. Yannas, L.J. Gibson, Design of a multiphase osteochondral scaffold III: Fabrication of layered scaffolds with continuous interfaces, J. Biomed. Mater. Res. Part A, 92(3):1078-93, 2010.
  • B.A. Harley, H.-D. Kim, M.H. Zaman, I.V. Yannas, D.A. Lauffenburger, L.J. Gibson, Micro-architecture of three-dimensional scaffolds influences cell migration behavior via junction interactions, Biophys. J., 95(8):4013-24, 2008.
  • B.A. Harley, J.H. Leung, E. Silva, L.J. Gibson, Mechanical characterization of collagen-glycosaminoglycan scaffolds, Acta Biomater., 3(4):463-474, 2007.
  • F.J. OBrien, B.A. Harley, I.V. Yannas, L.J. Gibson, The effect of pore size and structure on cell adhesion in collagen-GAG scaffolds, Biomaterials, 26(4):433-441, 2005.

Honors

  • Fellow, American Institute for Medical and Biological Engineering (AIMBE), 2019
  • Campus Distinguished Promotion Award, University of Illinois, 2018.
  • Dean’s Award for Excellence in Research (Associate Professor); College of Engineering, University of Illinois, 2018.
  • Dean's and Provost’s Awards for Excellence in Undergraduate Teaching, University of Illinois, 2018.
  • Invited participant, Frontiers of Engineering, National Academy of Engineering, 2016.
  • Schaefer Faculty Scholar, University of Illinois, 2016 - 2019.
  • Fellow, Center for Advanced Study, University of Illinois at Urbana-Champaign, 2015 - 2016.
  • University of Illinois Campus Distinguished Promotion Award, 2015.
  • Fellow, American Association for the Advancement of Science (AAAS), 2014
  • Young Investigator Award, Society for Biomaterials, 2014
  • NSF CAREER award 2013 - 2018
  • University of Illinois, Teachers Ranked as Excellent 2009 - present
  • Kirschstein National Research Service Award T32 Postdoctoral Fellowship, National Heart Lung and Blood Institute, NIH 2006-2008

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