BIOMED PhD Thesis Defense

Title:
Understanding and Tuning Macrophage Phenotype in Volumetric Muscle Loss (VML) Injury

Speaker:
Ricardo Checchia Whitaker, PhD Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University

Advisor:
Kara Spiller, PhD
URBN Professor of Biomedical Innovation
School of Biomedical Engineering, Science and Health Systems
Drexel University

Details:
Volumetric Muscle Loss (VML) is defined as the sudden loss of 20% or more of muscle mass, leading to tissue impairment. The current standard of care, consisting of rehabilitation, surgery, or amputation, is clearly ineffective. The sole therapy in clinical trials attempts to promote tissue regeneration via implantation of a decellularized matrix scaffold, nonetheless this approach also falls short of entirely reestablishing tissue function. The existing gap in knowledge behind the underpinning mechanisms driving VML pathology hinders the development of better therapeutics.

Recent studies uncovered the presence of dysfunctional macrophages following critical size VML injuries. Macrophages have been shown in vitro and in other models of muscle repair to be crucial for muscle regeneration due to its vital influence on supporting cells, such as stem cells, endothelial cells, and fibroblasts. Nonetheless, the mechanism(s) driving macrophages dysfunction following VML remain elusive. The goals of this thesis are to establish these mechanisms driving immune dysregulation, particularly on macrophages following VML, and make strides on the development of better therapeutics.

In this work, we have established a full timeline of macrophage dysfunction, both in the protein and gene level, from injury onset to the establishment of fibrosis. Next, we have uncovered previously unknown systemic changes in immune response, such as immune cell presence in the bone marrow, changes in splenic macrophage phenotype and blood serum cytokine levels, derived from this localized injury. In addition, we identified neutrophils as potential mediator of macrophage dysfunction. Lastly, we identified potential drugs and biomaterials to leverage a novel macrophage cell therapy approach for the treatment of VML.

The results from this thesis deepen our knowledge on some of the previously unknown mechanisms driving immune dysfunction and therefore tissue impairment after VML. It also lays down groundbreaking advances in possible treatments for VML patients.

BIOMED Seminar

Title:
Medical Device Risk Management

Speaker:
Bijan Elahi
Educator and Advisor
Product Safety and Risk Management
Medtronic

Details:
Safety risk management of medical devices is governed by the international standard: ISO 14971.  Besides understanding the formal requirements of ISO 14971, successful risk management requires the precise use of language as defined in the standard.  Conformance to ISO 14971 is a regulatory requirement, but it also brings many other benefits, which will be discussed.
 
Who should own and lead the performance of risk management?  Typically, Quality Assurance dept. takes on this role.  But this task is better suited to Systems Engineering.  Risk management requires multidisciplinary skills that go beyond the technical aspects.  For example, psychology, philosophy, logic, statistics, and more.  Even culture has an impact on risk management.

Biosketch:
Bijan Elahi has worked in risk management for medical devices for over 30 years at the largest medical device companies in the world, as well as small startups. He is a Technical Fellow, and the Medtronic corporate Advisor on safety risk management of medical devices. In this capacity, he offers education and consulting on risk management to all Medtronic business units, worldwide. Bijan is a lecturer at Eindhoven University of Technology (Netherlands), where he teaches risk management to doctoral students in engineering. At the invitation of the FDA, he teaches a graduate course on medical device risk management at Drexel University (Philadelphia, USA).

Bijan Elahi is the founder of MedTech Safety, Inc., an education and advisory company. He has educated over 10,000 individuals worldwide with outstanding results. Bijan is a frequently invited speaker at international professional conferences, and is also a contributor to ISO 14971, the international standard on the application of risk management to medical devices. He is the author of the best-selling book: Safety Risk Management for Medical Devices, published by Elsevier publishing.

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