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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.
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. Matls., 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, 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, 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, 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," Journal of Immunology, 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, Nature 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, Tissue Engineering, 19(9-10):1100-12, 2013.
E.A. Gonnerman, D.O. Kelkhoff, L.M. McGregor, B.A.C Harley, âAnisotropic collagen-GAG scaffolds promote HL-1 cardiomyocyte beating,â 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," Analytical Chemistry, 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
A. Sannino, L. Silvestri, M. Madaghiele, B. Harley, I.V. Yannas, "Modeling the fabrication process of micropatterned macromolecular scaffolds for peripheral nerve regeneration," Journal of Applied Polymer Science, 116, 1879-1888 (2010).
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, 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, 1066-77 (2010).
B.A. Harley, A.K. Lynn, Z. Wissner-Gross, W. Bonfield, I.V. Yannas, L.J. Gibson, "Design of a multiphase osteochondral scaffold I: Control of chemical composition," J. Biomed. Mater. Res. Part A, 92, 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, 4013-24, (2008).
K.H. Kim, T. Ragan, K. Bahlmann, M.J.R. Previte, B.A. Harley, D.M. Wiktor-Brown, C.A. Hendricks, B.P. Engelward, M.S. Stitt, K.H. Almeida, P.T.C. So, "Three-dimensional tissue cytometer based on high-speed multiphoton microscopy," Cytometry A, 71, 991-1002, (2007).
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, 811-823 (2007).
B.A. Harley, T.M. Freyman, M.Q. Wong and L.J. Gibson, "A new technique for calculating individual dermal fibroblast contractile forces generated within collagen-GAG scaffolds," Biophys. J., 93, 2911-2922 (2007).
B.A. Harley, J.H. Leung, E.C.C.M. Silva, L.J. Gibson, Mechanical characterization of collagen-glycosaminoglycan scaffolds. Acta Biomaterialia, 3, 463-474 (2007).
F.J. O'Brien, B.A. Harley, M.A. Waller, I.V. Yannas, L.J. Gibson and P.J. Prendergast, "The effect of pore size on permeability and cell attachment in collagen scaffolds for tissue engineering," Technol. Health Care, 15 3-17 (2007).
E. Farrell, F.J. O'Brien, E. Byrne, P. Doyle, J. Fischer, I.V. Yannas, B.A. Harley, B. O'Connell, P.J. Prendergast, and V.A. Campbell, "A collagen-glycosaminoglycan scaffold supports adult rat mesenchymal stem cell differentiation along the osteogenic and chrondrogenic routes," Tissue Engineering, 12, 459-468 (2006).
B.A. Harley, A.Z. Hastings, I.V. Yannas and A. Sannino, "Fabricating tubular scaffolds with a radial pore size gradient by a spinning technique," Biomaterials, 27, 866-874 (2006).
F.J. O'Brien, B.A. Harley, I.V. Yannas, and L.J. Gibson, "The effect of pore size and structure on cell adhesion in collagen-GAG scaffolds," Biomaterials, 26, 433-441 (2005).
B.A. Harley, M.H. Spilker, J.W. Wu, K.A. Asano, H.-P. Hsu, M. Spector, I.V. Yannas, "Optimal degradation rate for collagen chambers used for regeneration of peripheral nerves over long gaps," Cells Tissues Organs, 176, 153-165 (2004).
NSF CAREER award 2013 - 2018
Presidents Award, Research (Advocate of the Year); American Cancer Society of Illinois 2011
Engineering Council Award for Excellence in Advising, College of Engineering, University of Illinois 2011
University of Illinois, Teachers Ranked as Excellent 2009 - 2012
Kirschstein National Research Service Award T32 Postdoctoral Fellowship, National Heart Lung and Blood Institute, NIH 2006-2008
Fellowship, MIT-Whitaker Health Science Fund 2003-2005
Fellowship, Dupont/MIT Alliance 2000-2001