Brendan A. Harley
Contact Information:
e-mail:
Dr. Harley joins our faculty August 2008.
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
- Fellowship, Dupont/MIT Alliance 2000-2001
- Fellowship, MIT-Whitaker Health Science Fund 2003-2005
- Kirschstein National Research Service Award T32 Postdoctoral Fellowship, National Heart Lung and Blood Institute, NIH 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
B.A. Harley, L.J. Gibson, "In vivo and in vitro applications of collagen-GAG
scaffolds," In Press, Chemical Engineering Journal, (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).
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).
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. Harley, and I.V. Yannas, "Induced peripheral nerve regeneration using scaffolds," Minerva Biotecnologica, 19, 97-120 (2006).
E. Farrell, F.J. O'Brien, P. Doyle, J. Fischer, I. 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 osteogenic
and chondrogenic routes," Tissue Engineering, 12, 459-468 (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).
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 on cell adhesion in collagen-GAG scaffolds," Biomaterials,
26, 433-441 (2005).
F.J. O'Brien, B.A. Harley, I.V. Yannas and L. Gibson, "Influence of
freezing rate on pore structure in freeze-dried collagen-GAG scaffolds," Biomaterials,
25, 1077-1086 (2004).
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).
