Joshua C. Doloff, Ph.D.
BME Faculty Candidate and Guest Speaker
Massachusetts Institute of Technology

“Breaking down the immunobiology of implant fibrosis/foreign body response”

Abstract:

Implanted biomedical devices comprise a major component of modern medicine and are essential for many clinical applications ranging from tissue repair/reconstruction, electrical pacing/stimulation, controlled release, glucose sensing, and cell transplantation. However, a huge impediment to their therapeutic performance and lifespan, host immune-mediated foreign body response, results in their being walled off behind dense layers of fibrotic scar tissue. The first part of my talk will focus on systems biology approaches, including serial or combined innate and adaptive immune perturbations to elucidate immune-mediated rejection and fibrotic sequestration of biomaterial medical device implants. Identification of core innate and adaptive immune cell players will be discussed. Furthermore, cytokine and cytokine receptor array analysis in conjunction with cell sorting, antibody-based neutralization and small molecule inhibition will be presented in the context of identifying more selective targets in the fibrotic cascade. Throughout, multiple tissue implant sites, biomaterials, multi-component devices, and animal models, including non-human primates and a newly developed humanized mouse model, will also be presented. The last part of my talk will focus on leveraging this information toward the design of next generation technologies, including implant architecture, surface chemistries, and long-term controlled release systems, for successful elimination of rejection by modulating immune response.