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
- 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.
- 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).
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
- K.R.C. Kinneberg, A. Nelson, M. Stender, A.H. Aziz, L.C. Mozdzen, B.A.C. Harley, S.J. Bryant, V.L. Ferguson, ‘Reinforcement of mono- and bi-layer poly(ethylene glycol) hydrogels with a fibrous collagen,’ Ann. Biomed. Eng., 2015.
- J.C. Pence, K.B.H. Clancy, B.A.C. Harley, ‘The induction of pro-angiogenic processes within a collagen scaffold via exogenous estradiol and endometrial epithelial cells,’ Biotechnol. Bioeng., 2015.
- J.C. Lee, C. Pereira, X. Ren, W. Huang, D.W. Weisgerber, D.T. Yamaguchi, B.A. Harley, T.A. Miller, ‘Optimizing collagen scaffolds for bone engineering: effects of crosslinking and mineral content on structural contraction and osteogenesis,’ J. Craniofac. Surg., 2015.
- R.A. Hortensius, J.R. Becraft, D.W. Pack, B.A.C. Harley, The effect of glycosaminoglycan content on polyethylenimine-based gene delivery within three-dimensional collagen-GAG scaffolds, Biomater. Sci., 3(4):645-54, 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.
- D.W. Weisgerber, S.R. Caliari, B.A.C. Harley, Selective addition of mineral into collagen scaffolds to enhance hMSC osteogenesis and matrix remodeling, Biomater. Sci., 3(3):533-42, 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.
- W. Chen, K.D. Long, H. Yu, Y. Tan, J.S. Choi, B.A.C. Harley, B.T. Cunningham, Enhanced live cell imaging via photonic crystal enhanced fluorescence microscopy, Analyst, 139(22):5954-63, 2014.
- J.M. Banks, L.C. Mozdzen, B.A.C. Harley*, R.C. Bailey*, The combined effects of matrix stiffness and growth factor immobilization on the bioactivity and differentiation capabilities of adipose-derived stem cells, Biomaterials, 35(32):8951-9, 2014. *co-corresponding authors.
- A.T. Alsop, J.C. Pence, D.W. Weisgerber, B.A.C. Harley, R.C. Bailey, Photopatterning of VEGF within collagen-GAG scaffolds can induce a spatially confined response in human umbilical vein endothelial cells, Acta Biomater., 10(11):4715-22, 2014.
- J.C. Pence, E.A. Gonnerman, R.C. Bailey, B.A.C. Harley, Strategies to balance covalent and non-covalent biomolecule attachment within collagen-GAG biomaterials, Biomater. Sci., 2(9):1296-1304, 2014.
- S.R. Caliari, B.A.C. Harley, Collagen-GAG scaffold biophysical properties bias MSC lineage choice in the presence of mixed soluble signals, Tiss. Eng. A, 20(17-18):2463-72, 2014.
- 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.
- W. Chen, K.D. Long, M. Lu, V. Chaudhery, H. Yu, J.S. Choi, J. Polans, Y. Zhuo, B.A.C. Harley, B.T. Cunningham, Photonic crystal enhanced microscopy for imaging of live cell adhesion, Analyst, 138(20):5886-94, 2013.
- D.W. Weisgerber, D.O. Kelkhoff, S.R. Caliari, B.A.C. Harley, The impact of discrete compartments of a multi-compartment collagen-GAG scaffold on overall construct biophysical properties, J. Mech. Behav. Biomed. Matls., 28:26-36, 2013.
- 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.
- N.P. Gabrielson, A.V. Desai, B. Mahadik, M.-C. Hofmann, P.J.A. Kenis, B.A.C. Harley, Cell-laden hydrogels in integrated microfluidic devices for long-term cell culture and tubulogenesis assays, Small, 9(18):3076-81, 2013.
- S. Pedron, B.A.C. Harley, The impact of the biophysical features of a 3D gelatin microenvironment on glioblastoma malignancy, J. Biomed. Mater Res. Pt. A, 101(12):3404-15, 2013.
- S.-Y. Park, P. Wolfram, K. Canty, B.A. Harley, C. Nombela-Arrieta, G. Pivarnik, J. Manis, H.E. Beggs, L.E. Silberstein, Focal adhesion kinase regulates the localization and retention of pro-B Cells in bone marrow microenvironments, J. Immunol., 190(3):1094-102, 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.
- S.R. Caliari, B.A.C. Harley, Composite growth factor supplementation strategies to enhance tenocyte bioactivity in aligned collagen-GAG scaffolds, Tiss. Eng. A, 19(9-10):1100-12, 2013.
- E.A. Gonnerman, D.O. Kelkhoff, L.M. McGregor, B.A.C Harley, The promotion of HL-1 cardiomyocyte beating using anisotropic collagen-GAG scaffolds, Biomaterials, 33(34):8812-21, 2012.
- J.F. Frisz, J.S. Choi, R.L. Wilson, B.A.C. Harley, M.L. Kraft, Identifying differentiation stage of individual primary hematopoietic cells from mouse bone marrow by multivariate analysis of TOF-secondary ion mass spectrometry data, Anal. Chem., 84(10):4307-13, 2012.
- 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, D.W. Weisgerber, M.A. Ramirez, D.O. Kelkhoff, B.A.C. Harley, The influence of collagen-glycosaminoglycan scaffold relative density and microstructural anisotropy on tenocyte bioactivity and transcriptomic stability, J. Mech. Behav. Biomed. Matls., 11:27-40, 2012.
- S.R. Caliari, M. Ramirez, B.A.C. Harley, The development of collagen-GAG scaffold-membrane composites for tendon tissue engineering, Biomaterials, 32(34):8990-8998, 2011.
- 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, A.K. Lynn, Z. Wissner-Gross, W. Bonfield, I.V. Yannas, L.J. Gibson, Design of a multiphase osteochondral scaffold II: Fabrication of a mineralized collagen-GAG scaffold, J. Biomed. Mater. Res. Part A, 92(3):1066-77, 2010.
- A.K. Lynn, S.M. Best, R.E. Cameron, B.A. Harley, I.V. Yannas, L.J. Gibson, W. Bonfield, Design of a multiphase osteochondral scaffold I: Control of chemical composition, J. Biomed. Mater. Res. Part A, 92(3):1057-65, 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.
- Y. Le, B. Zhu, B. Harley, S.-Y. Park, J.P. Manis, H.R. Luo, A. Yoshimura, L. Hennighausen, L.E. Silberstein, SOCS3 protein developmentally regulates the chemokine receptor CXCR4-FAK signaling pathway during B lymphopoiesis, Immunity, 27(5):811-823, 2007.
- 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.