Excellence in Research: Biodegradable composite nanofiber meshes that contain degradable metal particulates

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Non-technical Summary: A significant challenge in the field of biomedical engineering is that many implanted devices stimulate immune reactions that can interfere with tissue healing. Composite biomaterials that mimic the properties of the tissue matrix promote faster healing of damaged tissue and wounds. Recent methods incorporate a relatively unexplored type of material: degradable metal particles in polymer composites. As these metals degrade, they release metal ions and other degradation products that are beneficial for injured tissues. However, both can damage tissues and cells if applied in excess. In this HBCU EIR project, the team will study these biodegradable materials with the goal of developing a family of biomaterials for tissue delivery of beneficial degradation products of metals to promote wound healing. One broader impact of this project is to enhance knowledge of biodegradable metals to address the significant needs for researchers and medical practitioners to repair multiple types of tissue injuries. Another remarkable broader impact of this project includes establishing educational practices that enhance the engagement of undergraduate and graduate students, with a particular focus on including underrepresented and at-risk minorities students in STEM research training in this area. Educational efforts will include graduate research projects, summer research projects for undergraduate students, and K-12 student outreach and training opportunities. Technical Summary:The biodegradable metals Mg and Zn in the physiological environment release Mg2+ and Zn2+, which, along with other degradation products, have shown the potential to improve tissue healing. Degradation rates of these metals are highly dependent on the size and surface area exposed. In the case of Mg and Zn, both metals are dependent on the synthesis, post-synthesis and transport/storage conditions, since the metal is prone to oxidize very quickly when exposed to the ambient environment. It is currently a challenge to obtain precise control over these variables. A robust synthesis methodology will be developed to control size and surface properties of the Mg and Zn particles in an inert environment, which will further control degradation and release rates of metal ions. Electrospun nanofiber composites of biocompatible polymers, poly-lactic-glycolic acid (PLGA) and PLGA-chitosan (CH), containing embedded metal particles, will be developed, with the ultimate goal of producing a series of material formulations that will allow fine control over the release rate of metal ions. These composites will be tested in vitro using fibroblast and macrophage co-cultures to identify optimal properties of the composites and metal particles loading. Innovative elements of this proposal are, first, controlling the size of Mg and Zn particles to allow control over amounts; second, embedding these in ECM-mimicking nanofibers of PLGA and PLGA-CH to provide exquisite control over metal particle degradation; and third, testing the composite by exposing it to cells in vitro to reduce fibroblast fibrotic responses and inflammation. The biodegradable metal-embedded nanofiber composite achieved via this project will provide a better understanding of the inherent healing properties of tissue including reducing infection, stimulating recovery from inflammation, and enhancing tissue remodeling. In this project, the broader impact of the proposed work will be enhanced by public education and by creating research opportunities for significant numbers of underrepresented minority students, with training and mentoring focused on real-world biomaterials research in NC A&T’s College of Engineering.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.