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BIOE Seminar Series: James Bryers
Friday, October 20, 2017
9:00 a.m.
Pepco Room (1105), Jeong H. Kim Engineering Building
For More Information:
Dr. Steven Jay
smjay@umd.edu

Dr. James Bryers
Professor, Department of Bioengineering
University of Washington

Biomaterials for Immunomodulation

A rapidly growing field of research is the design of implantable scaffolds and hydrogels made of synthetic and natural materials, with ability to modulate the immune response. Greater understanding of the molecular basis of cellular phenomenon such as apoptosis, receptor-ligand interactions, innate and adaptive immune cell response, and tissue regeneration has intensified the development of materials-based therapeutic strategies. This seminar will highlight two examples of biomaterials immunomodulation.

First example: Classical vaccine/adjuvant combinations are notoriously inefficient at transfecting DCs in vivo. While adjuvants have reduced the required vaccine dose, their design is mostly art.  Only recently, due to the needs of cancer immunotherapies, has the biomaterials/gene delivery community begun to develop new strategies for vaccine delivery.  Three-dimensional (3D) polymer scaffolds may be ideal for quantitatively manipulating directly in the body dendritic cell (DC) recruitment, antigen uptake and activation, and migration to the lymph nodes, due to their established success in controlled drug and cell delivery.  Nosocomial infections are the fourth leading cause of death in the U.S. with ~60% of these infections being biofilms associated with some type of implanted medical device. The overall financial impact of biofilm-based infections is estimated to be in the tens of billions of dollars per year. Here, results of a unique 3D porous scaffold vaccine platform designed to enhance immune response against biomedical devise based infections will be presented.

Second example. We have developed Porous Templated Scaffolds (PTS)where every pore is uniformly controlled (narrow pore size distribution) throughout the scaffold and the pore interconnects are also uniform in size, with both parameters being adjustable. Without the use of any signaling/stimulating molecules (released or tethered), if the pore size is ~40µm, PTS show no chronic inflammation or foreign body response while promoting remarkable healing in numerous soft and hard tissue applications; regardless of the polymer used. Growing evidence suggests that transcriptional regulators and miRNA molecules encapsulated within membrane vesicles (i.e., exosomes, microvesicles) that are released by a parent cell can modify the phenotype of recipient cells. Extracellular vesicles (EVs) can present on their surfaces host membrane cell markers and can internally carry proteins (e.g., transcription factors), bioactive lipids, and nucleic acids (mRNAs, miRNAs). Here, preliminary data suggesting that macrophages and T cells in only 40µm pore size PTS generate EVs with unique miRNA content capable of re-programming somatic myeloid cells into desired tissue cells (trans-differentiation) will be presented.

 

 


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