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The goal of our research program is to develop innovative biomaterial approaches to replicate the heterotypic cell and matrix microenvironments found in the tissues, organs, and stem cell niches of the body. They present unique, unaddressed challenges in tissue engineering, but also inspire innovative biomaterials science. We are particularly interested in strategies to render a biomaterial instructive – having the capacity to selectively influence cell bioactivity.
Therefore, whereas many research efforts in the field of tissue engineering focus on optimizing monolithic biomaterials, we focus on developing biomaterials that utilize spatially and temporally defined patterns of structural, biochemical, and cellular microenvironments to drive cell fate. Our efforts are generating new insight regarding the design of spatially-graded biomaterials able to regionally control (stem) cell activity for a wide range of tissue engineering and regenerative medicine applications.
Key focus areas include: (1) multi-scale scaffolds to drive orthopedic interface regeneration (osteotendinous insertion, maxillofacial polytrauma); (2) bone marrow mimics to investigate hematopoietic stem cell expansion and homing; (3) brain tumor biomaterial platform to dissect the mechanobiology of glioblastoma cell-matrix interactions and to screen pharmaceutical/immune-therapies; (4) approaches to control transient/permanent sequestration of endometrium-inspired biomolecules within a biomaterial to drive revascularization.
While primarily experimental, our efforts are enriched by modeling approaches as well as inspiration derived from mechanically-efficient structures found in nature such as porcupine quills, plant stems, and interdigitated sutures to improve biomaterial design. Notably, the porous structure of biomaterials and many natural materials (wood, coral) gives rise to distinct mechanical and material properties such as exceptional mechanical efficiency. Therefore as part of our efforts, we use cellular solids and poroelastic modeling techniques to describe local properties within the biomaterials we create.
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).
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