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Breaking down the immunobiology of implant fibrosis/foreign body response
A Medicine by Design, Ted Rogers Centre for Heart Research and IBBME Special Seminar.
Joshua C. Doloff, PhD
JDRF Senior Postdoctoral Fellow, Department of Chemical Engineering, David H. Koch Institute, Massachusetts Institute of Technology, and
Boston Children’s Hospital / Harvard Medical School
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.
Joshua C. Doloff is a Juvenile Diabetes Research Foundation (JDRF) senior postdoctoral fellow in the labs of Robert Langer and Daniel G. Anderson in the Department of Chemical Engineering and the David H. Koch Institute for Integrative Cancer Research at MIT and Boston Children’s Hospital.
Prior, while earning his undergraduate degree in biomedical engineering at the University of Pennsylvania, he carried out biomaterials research, utilizing bioabsorbable calcium and phosphate-based silica sol-gel scaffolds to support bone matrix regeneration.
In an endeavour to better understand what happens when deliverables are introduced into the body, Joshua focused his PhD research at Boston University on host immune responses to varied therapeutics. His early work on genetic engineering of cancer-targeted viral vectors won technology development and University Provost awards.
In the latter half of his PhD, he focused on chemotherapeutic modulation that elicited potent anti-tumor immune response.
Highlighting his achievements, Joshua was awarded the Frank A. Belamarich Award for Best Doctoral Research across all fields in his graduating class.
At MIT, Josh merged his expertise to elucidate and overcome immune-mediated foreign body response and host rejection of macroscale biomaterial and biomedical device implants.
This work has contributed to numerous awarded or pending patents, a number of which helped form the basis of new lab startup Sigilon, and has been recognized by his peers in various forms, including publications in multiple Nature-tier journals, invited speaker engagements, and awards including top presentation selections, a first place Immunoengineering prize at the 2017 Society for Biomaterials symposium, and a co-chair invitation at this year’s upcoming annual BMES meeting.