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

非技术总结：生物医学工程领域的一个重大挑战是，许多植入设备刺激免疫反应，可能干扰组织愈合。模拟组织基质特性的复合生物材料促进受损组织和伤口的更快愈合。最近的方法结合了一种相对未开发的材料类型：聚合物复合材料中的可降解金属颗粒。当这些金属降解时，它们释放出金属离子和其他对受损组织有益的降解产物。然而，如果过量使用，两者都会损害组织和细胞。在这个HBCU EIR项目中，该团队将研究这些可生物降解的材料，目标是开发一系列生物材料，用于组织输送金属的有益降解产物，以促进伤口愈合。该项目的一个更广泛的影响是提高对可生物降解金属的认识，以满足研究人员和医疗从业人员修复多种类型组织损伤的重大需求。该项目的另一个显著的更广泛的影响包括建立教育实践，加强本科生和研究生的参与，特别注重在这一领域的STEM研究培训中包括代表性不足和处于风险中的少数民族学生。教育工作将包括研究生研究项目，本科生暑期研究项目，以及K-12学生的推广和培训机会。技术总结：可生物降解的金属Mg和Zn在生理环境中释放Mg 2+和Zn 2+，它们沿着其他降解产物，显示出改善组织愈合的潜力。这些金属的降解速率在很大程度上取决于暴露的尺寸和表面积。在Mg和Zn的情况下，两种金属都取决于合成、合成后和运输/储存条件，因为金属在暴露于周围环境时易于非常快速地氧化。目前，对这些变量进行精确控制是一项挑战。将开发一种稳健的合成方法来控制惰性环境中Mg和Zn颗粒的尺寸和表面性质，这将进一步控制金属离子的降解和释放速率。将开发含有嵌入金属颗粒的生物相容性聚合物聚乳酸-乙醇酸（PLGA）和PLGA-壳聚糖（CH）的静电纺丝复合材料，其最终目标是生产一系列材料配方，这些材料配方将允许对金属离子的释放速率进行精细控制。这些复合材料将在体外使用成纤维细胞和巨噬细胞共培养物进行测试，以确定复合材料和金属颗粒负载的最佳性能。该提案的创新要素是，首先，控制Mg和Zn颗粒的大小以允许控制量;第二，将它们嵌入PLGA和PLGA-CH的ECM模拟纳米纤维中，以提供对金属颗粒降解的精确控制;第三，通过将其暴露于体外细胞来测试复合材料，以减少成纤维细胞纤维化反应和炎症。通过该项目实现的可生物降解的金属嵌入式复合材料将更好地了解组织的固有愈合特性，包括减少感染，刺激炎症恢复和增强组织重塑。在这个项目中，拟议工作的更广泛影响将通过公共教育和为大量代表性不足的少数民族学生创造研究机会来加强，并在NC A T工程学院进行针对现实世界生物材料研究的培训和指导&。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛影响进行评估来支持审查标准。

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.