Condensed tannin polymers as a new functional biomaterials

缩合单宁聚合物作为新型功能性生物材料

• 批准号: 2306983
• 负责人: Matthew Kipper
• 金额: $ 45万
• 依托单位: Colorado State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2306983&HistoricalAwards=false
• 关键词: Condensed; tannin; polymers; new; functional

Non-technical abstractMedical implants can cause biological responses such as bacterial infection and inflammation. In normal healing, body’s immune system helps to fight infection and remove damaged tissue. Inflammation should be temporary, and should wane as new healthy tissue is formed, but prolonged inflammation can delay or prevent healing. Prolonged inflammation can damage not only the surrounding tissue but also the implant material through a chemical process called oxidation. In severe cases of unresolved inflammation or infection implants must be removed or replaced. While much is known about how foreign materials lead to inflammation, very little is known about how they can promote the resolution of inflammation and subsequent tissue healing. These problems could be addressed by development of new materials that promote the resolution of inflammation. This work proposes a solution inspired by biology. Plants produce materials called “condensed tannins” that protect plant tissues from bacterial and fungal pathogens and from the harmful effects of oxidation. This work will develop new materials for implants based on these condensed tannins. Condensed tannins will be modified so that they can guide inflammatory responses, and thereby promote healing, while also imparting antioxidant and antibacterial activity to implant surfaces. This work will also discover how these new materials modulate other outcomes related particularly to bone healing, such as stem cell growth and mineralization, so that the work can be translated to orthopedic implants. These new biomaterials based on condensed tannins will be developed from an abundant renewable resource, and they will provide new strategies for improving healing around implants. This work will yield new insights into the design of functional biomaterials that promote healing, reduce oxidation related damage, and fight infections. An international collaborator will contribute to a graduate course in global engineering and entrepreneurship. Outreach to the public will communicate how sustainable materials from abundant renewable resources can solve important challenges in medicine.Technical abstractThe ideal of a “bioinert” biomaterial has not been realized. Materials in contact with biological environments adsorb proteins, which can induce inflammatory responses. Prolonged inflammation can cause oxidative damage to tissues and materials, and inhibit wound healing, leading to implant failure. Condensed tannins are a class of plant-derived polyphenols, with excellent processing characteristics and valuable biological properties. Cellular responses to materials containing a commercially available, amphoteric aminated condensed tannin called tanfloc have been reported. This work hypothesizes that the chemistry of condensed tannins can be modified to modulate important biological responses to condensed tannin-based materials. This work aims to (i) chemically modify tanfloc to alter its acidity, basicity, and antioxidant activity; (ii) use the chemical modification to modulate protein binding, thereby modulating the polarization of macrophages, cellular inflammation, and antibacterial activity; and (iii) use the chemical modification to modulate mesenchymal stem cell differentiation and mineralization that are related to bone healing. Outcomes on surfaces containing the new condensed tannin derivatives will be compared to surfaces modified with polydopamine (a biopolymer with similar catecholamine chemistry to tanfloc), to oligoethylene glycol surfaces (presenting hydrogen bond acceptors but no acidic or basic groups), and to other materials commonly used in bone tissue engineering. This proposed work will produce three new condensed tannin derivatives, containing either increased (phenolic) acidity, increased (quaternary amine) basicity, or increased ether (o-methyl ether) functional groups, with well-characterized polyelectrolyte behavior, antioxidant activity, and degradation kinetics. This work will elucidate structure-property relationships that demonstrate how condensed tannin chemistry can be altered to modulate protein binding, macrophage polarization, phagocytosis, foreign body giant cell formation, and antibacterial activity. This work will also demonstrate that the chemistry of condensed tannins can modulate stem cell differentiation and mineralization on surfaces. The work will broaden participation of undergraduate and masters students in the research program.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.

非技术抽象中介的不强制性可能会引起生物学反应，例如细菌感染和感染。在正常的愈合中，身体的免疫系统有助于抵抗感染并去除损坏的组织。炎症应该是暂时的，并且随着新的健康组织的形成，但长期感染会延迟或阻止愈合。长时间的感染不仅会损害周围的组织，还会通过称为氧化的化学过程损害植入物材料。必须清除或更换严重的未解决感染或感染侵略的病例。尽管对外国材料如何导致感染知之甚少，但对于如何促进感染和随后的组织愈合的分辨率知之甚少。这些问题可以通过开发促进感染解决的新材料来解决。这项工作提出了一种受生物学启发的解决方案。植物生产的材料称为“凝结的单宁”，可保护植物组织免受细菌和真菌病原体的影响，并免受氧化的有害作用。这项工作将根据这些凝结的单宁开发新材料，以供粉碎。凝结的单宁将被修饰，以便它们可以引导炎症反应，从而促进愈合，同时还将抗氧化剂和抗菌活性赋予植入物表面。这项工作还将发现这些新材料如何调节其他与骨骼愈合有关的结果，例如干细胞生长和矿化，以便将工作转化为骨科关闭。这些基于凝结单宁的新生物材料将从丰富的可再生资源中开发出来，它们将提供改善围绕Imprans治疗的新策略。这项工作将对功能性生物材料的设计产生新的见解，这些功能生物材料促进愈合，减少氧化有关的损害和抗击感染。国际合作者将为全球工程和企业家精神的研究生课程做出贡献。向公众推广将传达出可持续的可再生资源可持续材料如何解决医学中的重要挑战。技术摘要尚未实现“生物启动”生物材料的理想。与生物环境接触的材料吸附蛋白，可以诱导炎症反应。长时间的炎症会对组织和材料造成氧化损害，并抑制伤口愈合，导致植入物衰竭。凝结的单宁是一类植物来源的多酚，具有出色的加工特征和有价值的生物学特性。据报道，据报道，据报道，据报道，据报道，据报道，据报道，据报道，据报道，据报道，据报道，据报道，据报道，据报道，据报道，含有商业可用的，两性成功的凝结的单宁称为tanfloc的材料。这项工作假设可以修改冷凝单宁的化学性质，以调节对基于单宁的材料的重要生物学反应。这项工作的目的是（i）化学修改tanfloc以改变其酸度，碱性和抗氧化活性； （ii）使用化学修饰来调节蛋白质结合，从而调节巨噬细胞的极化，细胞炎症和抗菌活性； （iii）使用化学修饰来调节与骨骼愈合有关的间充质干细胞分化和矿化。将含有新的冷凝的单宁衍生物表面的结果与用聚多巴胺（一种具有相似的catecholamine tan tanfloc化学化学的生物聚合物）的表面与寡甲基乙二醇表面进行了比较，但在氢键受体中（没有酸性或基本组），但没有酸性或基本材料），与其他材料中使用了其他材料。这项提出的工作将产生三种新的凝结的单宁衍生物，其中包含（酚类）酸度增加，增加（第四纪胺）碱性或增加的醚（O-甲基醚）官能团，具有良好的聚电解质行为，抗氧化活性，抗氧化活性和脱位动力学。这项工作将阐明结构特性关系，以证明如何改变凝结的单宁化学以调节蛋白质结合，巨噬细胞极化，吞噬作用，异物巨型细胞形成和抗菌活性。这项工作还将证明，凝结的单宁化学可以调节表面上的干细胞分化和矿化。这项工作将扩大本科生和硕士学生参与研究计划的参与。该奖项反映了NSF的法定任务，并通过使用基金会的知识分子优点和更广泛的影响审查标准来评估，以诚实的支持。