Brendan A. Harley
- Molecular, Cellular and Tissue Engineering
- 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
For more information
- Molecular, Cellular and Tissue Engineering
- Extracellular Matrix Analogs, Cell and Tissue Engineering
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.
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.
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).
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):7408â€“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.
- Stanford University, Bio-X Frontiers in Interdisciplinary Biosciences Seminar, 3/2019.
- Johns Hopkins University, Dept. of Chemical and Biomolecular Engineering, 11/2018.
- Brown University, Dept. of Biomedical Engineering, 10/2018.
- University of Massachusetts at Amherst, Dept. of Chemical Engineering, 3/2018.
- Keynote, 5th International Conference on Cellular and Molecular Bioengineering (ICCMB5), Nanyang Technological University, Singapore, 3/2018.
- Harvard University, School of Engineering and Applied Sciences, 2/2018.
- Duke University, Depts. of Biomedical Engineering and Orthopaedic Surgery, 2/2018.
- Cancer Research UK Cambridge Institute 10th Anniversary International Symposium: Multi-scale approaches to cancer biology, Cambridge, UK, 3/2017.
- University of Birmingham (U.K.), Dept. of Chemical Engineering, 2/2017.
- Plenary: Leaders in Biomaterials, AIChE Annual Meeting, San Francisco, CA, 11/2016.
- Gordon Research Conference: Signal Transduction by Engineered Extracellular Matrices, 6/2016.
- Keynote, Molecular, Cell and Tissue Bioengineering Symposia, Arizona State University, 4/2016
- Wake Forest Institute for Regenerative Medicine, Wake Forest University, 2/2016.
- Royal College of Surgeons in Ireland, 8/2015.
- Fraunhofer Institute for Interfacial Engineering and Biotechnology (Stuttgart, Germany), 7/2015.
- Georgia Tech, Dept. of Biomedical Engineering, 12/2014.
- Cornell University, Dept. of Chemical and Biomolecular Engineering, 9/2014.
- University of California Berkeley, Dept. of Bioengineering, 5/2014.
- University of Pennsylvania, Dept. of Bioengineering, 2/2014.
- University of California Santa Barbara, Dept. of Chemical Engineering, 2/2014.
- US-Japan Nano-Bio Workshop, Tsukuba/Kyoto, Japan, 12/2013.
- Boston University, Dept. of Biomedical Engineering, 12/2013.
- University of Wisconsin, Dept. of Bioengineering, 9/2013.
- Queen Mary University of London, School of Engineering and Materials Science (London, UK), 9/2012.
- Cambridge University Engineering Department (Cambridge, UK), 9/2012.
- Washington University in St. Louis, Dept. of Mechanical Engineering & Materials Science, 9/2011
- Institute of Stem Cell Research (Munich, Germany), 9/2008.
- Associate Editor, Science Advances.
- Editorial Board, Tissue Engineering.