Understanding the Role of Macrophage Phenotype in Biomaterial-Mediated Bone Regeneration
Tuesday, August 2, 2016
10:30 AM-12:30 PM
BIOMED PhD Research Proposal
Title:
Understanding the Role of Macrophage Phenotype in Biomaterial-Mediated Bone Regeneration
Speaker:
Pamela L. Graney, PhD Candidate, School of Biomedical Engineering, Science and Health Systems
Advisor:
Kara L. Spiller, PhD, Assistant Professor, School of Biomedical Engineering, Science and Health Systems
Abstract:
A major challenge in engineering tissues the repair of large bone defects is achieving sufficient vascularization to maintain tissue survival and integration. Functional blood vessel networks must not only form (angiogenesis) within the biomaterial, but also connect (anastomosis) with the existing vasculature to achieve perfusion of the tissue upon implantation. Currently, there is no known way to control anastomosis, preventing the translation of many potentially useful biomaterials in regenerative medicine.
Macrophages, the primary cells of the inflammatory response, play major roles in mediating bone repair and regulating the inflammatory response to implanted biomaterials; however, macrophages exhibit phenotypic plasticity ranging from pro-inflammatory “M1” to anti-inflammatory “M2”. M2 macrophages can also be further described as “M2a” or “M2c”, which are believed to promote tissue deposition and breakdown, respectively. Though studies have shown that the macrophage population shifts from predominantly M1 to predominantly M2 over time in response to environmental stimuli during normal bone repair, the phenotypic contributions of M1, M2a and M2c macrophages to bone repair and vascularization are not well understood. It is also unclear how biomaterials impact the microenvironment to modulate macrophage phenotype, and how this modulation subsequently affects vascularization and healing outcomes. Therefore, the proposed work aims to 1) understand how macrophages respond to biomaterials used in bone regeneration and 2) explore the impact of changing macrophage phenotype on biomaterial vascularization. We will first assess the in vitro response of macrophages to model biomaterials that exhibit varying degrees of success in regenerating large bone defects. Then, a novel 3D model of tissue vascularization will be adapted to systematically study the roles of M1, M2a and M2c macrophages in angiogenesis and anastomosis, both in vitro and in vivo, using live imaging, gene expression analysis, protein secretion analysis and immunohistochemistry in order to thoroughly characterize the crosstalk of macrophages and blood vessel networks.
Overall, this work will elucidate the role of the inflammatory response in biomaterial-mediated bone repair, which may inform the design of immunomodulatory biomaterials that promote vascularization and healing. Understanding how the inflammatory response regulates vascularization is also expected to have important implications for treating diseases associated with extensive blood vessel growth, such as cancer and autoimmune conditions, whereby vascularization of the tissue facilitates disease progression.
Contact Information
Ken Barbee
215-895-1335
barbee@drexel.edu