White Blood Cells and Tissue Regeneration

NIH funds research to study how neutrophils interact with new templates.

Dr. Gary Bowlin, professor and Herff Chair of Excellence in the Department of Biomedical Engineering, in collaboration with Dr. Marko Radic in the Department of Microbiology, Immunology, and Biochemistry at the University of Tennessee Health Science Center, has received a new grant from the National Institutes of Health (NIH) to study how neutrophils interact with tissue regeneration templates. In addition, they will design the templates used to promote regeneration of new tissues in the body to delivery and release compounds, focus on natural compounds, to regulate or attenuate (i.e., anti-inflammatory agents) the neutrophil responses associated with implanted templates.

Bowlin states, "We are grateful for the funding and excited to continue unraveling the mysterious neutrophil and its interaction with biomaterials and tissue regeneration templates."

Neutrophils, the innate immune system's first responders, rapidly and robustly swarm to a surgical-induced injury site containing an implanted fibrous tissue regeneration template. The understanding and modulation of the acute neutrophil response to such fibrous templates have been a recent focus in our lab and the field of biomaterials, seen as a key to improving tissue template regeneration efficacy for the in situ regeneration of new tissues and organs. This understanding, regulation, and attenuation are critical, knowing that acutely interacting neutrophils can secrete neutrophil extracellular traps (NETs) by NETosis, contributing to the early-stage development of neutrophil-derived fibrosis, creating a barrier on the templates.

Previously, we have demonstrated that the degree of NETosis can is regulated by electrospun fibrous template architecture and composition. The mechanisms driving NETosis by acutely interacting neutrophils interacting with the fibrous templates remain to be fully elucidated, thus hampering efforts to engineer regulation and attenuation approaches. This gap in fundamental knowledge is a significant problem because the acute NETosis and NET layer development on the template surface creates a hindrance by the blockage of the porous structure, restricting tissue integration and an actual, critically needed three-dimensional tissue regeneration capacity.

Upon successful completion, this study's expected outcome and innovation will elucidate the critical structural variables and therapeutic compound delivery in the refinement of fibrous regeneration templates to allow for critical three-dimensional tissue integration, free from the impediment of acute, surface NETs. These results will then translate to various degrees to other polymeric, fibrous tissue template compositions and designs to advance the field of template-induced tissue engineering and in situ regeneration in the treatment options for various disorders plaguing our society.

More importantly, this research will include a biomedical engineering Ph.D. student along with two biomedical engineering undergraduate research assistants, all hired as part of the grant funding in the performance of meritorious biomedical research. The group hopes to translate the results to novel, bioresorbable vascular graft development and other tissues and organs at the University of Memphis soon.

For more information on this research, contact Bowlin at glbowlin@memphis.edu.