School of Chemical Sciences   |   College of Liberal Arts & Sciences  |   College of Engineering

 

Brendan A Harley

Brendan A Harley

Contact Information:
e-mail:
phone: (217) 244-7112
fax: (217) 333-5052

110 Roger Adams Lab
MC-712, Box C-3
600 S. Mathews Ave.
Urbana, IL 61801

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

 

ORTHOPEDIC AND SOFT TISSUE ENGINEERING

The typical mammalian response to chronic and acute injuries is characterized by a complex inflammatory response, cell-mediated wound contraction, and scar tissue synthesis (repair). However, introduction of a suitable biomaterial such as a scaffold into the wound can block cell-mediated contraction and induce regeneration of physiological tissue. Specific projects include the use of uniform/monolithic, gradient, and layered scaffolds technologies to induce regeneration of a wide range of orthopedic and soft tissues, such as cartilage, bone, tendon, ligament, and peripheral nerves, following injury.

CELL BEHAVIORAL CUES

Cell motility, contraction, proliferation, and extracellular matrix protein biosynthesis are critical components of many physiological and pathological processes as well as in tissue engineering applications. These behaviors are modulated by a complex, spatio-temporally integrated set of biophysical mechanisms influenced not only by the biochemistry of extracellular and intracellular signaling, but also by the biophysics of the surrounding extracellular environment and of cell-cell interactions. In our research, we use a series of highly porous collagen-based scaffolds as a model extracellular matrix (ECM) system to study how distinct features of the local microenvironment influences cell behavior.

STEM CELL NICHE ENGINEERING

Adult stem cells have the capacity to remain quiescent for long periods of time, produce more stem cells of the same type, or give rise to a defined set of mature differentiated progeny. The stem cell niche is the local microenvironment surrounding a stem cell, consisting of multiple cells, mechanical influences, as well as soluble and insoluble regulators, that modulates stem cell behavior. We use hematopoietic and mesenchymal stem cells in concert with imaging and scaffold technologies as a platform for studying microenvironmental cues on stem cell behavior and for optimizing porous biomaterials and in vitro culture systems for stem cell engineering.

MODELING CELLULAR MATERIALS

Cellular solids include engineering materials such as foams for structural and biomedical purposes and porous scaffolds for tissue engineering applications, as well as natural materials like wood and coral. The porous (cellular) structure of these materials gives rise to many distinct mechanical and material properties such as exceptional mechanical efficiency on a per weight basis. The complex geometry and behavior of these porous materials are difficult to describe exactly, however. In our research, we use cellular solids and poroelastic modeling techniques as analytical tools to describe mechanical and microstructural features of biological tissues, tissue engineering scaffolds and gels, and intracellular features of individual cells such as the cytoskeleton.

Selected Publications

Scaffold Fabrication/Analysis:

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).

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).

In vivo Scaffold Applications:

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 (in press, 2009).

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 (in press, 2009).

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 (in press, 2009).

In vitro Scaffold Applications:

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).

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).

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).

Immunology/Hematopoiesis:

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).

Review Articles/Chapters:

B.A. Harley, L.J. Gibson, "In vivo and in vitro applications of collagen-GAG scaffolds," Chemical Engineering Journal, 137, 102-121 (2008).

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).

B. Harley, and I.V. Yannas, "Induced peripheral nerve regeneration using scaffolds," Minerva Biotecnologica, 19, 97-120 (2006).

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).