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.

非技术摘要医学植入物可引起生物反应，如细菌感染和炎症。在正常的愈合过程中，身体的免疫系统有助于抵抗感染和移除受损的组织。炎症应该是暂时的，随着新的健康组织的形成，炎症应该会减弱，但长期的炎症可能会推迟或阻止愈合。长期的炎症不仅会损害周围的组织，还会通过一种名为氧化的化学过程损害植入材料。在严重的炎症或感染情况下，必须取出或更换植入物。虽然关于异物如何导致炎症的了解很多，但对它们如何促进炎症的消退和随后的组织愈合却知之甚少。这些问题可以通过开发促进炎症消退的新材料来解决。这项工作提出了一种受生物学启发的解决方案。植物产生一种被称为“缩合单宁”的物质，它可以保护植物组织免受细菌和真菌病原体以及氧化的有害影响。这项工作将开发基于这些缩合单宁的植入物新材料。缩合单宁将被修饰，以引导炎症反应，从而促进愈合，同时还赋予植入物表面抗氧化和抗菌活性。这项工作还将发现这些新材料如何调节其他特别与骨愈合相关的结果，如干细胞生长和矿化，以便将这项工作转化为骨科植入物。这些基于缩合单宁的新生物材料将从丰富的可再生资源中开发出来，它们将为改善植入物周围的愈合提供新的策略。这项工作将为功能生物材料的设计带来新的见解，这些材料可以促进愈合，减少氧化相关的损害，并对抗感染。一名国际合作者将为全球工程和创业研究生课程做出贡献。面向公众的宣传将介绍如何从丰富的可再生资源中获得可持续材料，以解决医学领域的重大挑战。技术摘要“生物惰性”生物材料的理想尚未实现。接触生物环境的物质会吸附蛋白质，从而引发炎症反应。长期的炎症会对组织和材料造成氧化损伤，抑制伤口愈合，导致种植失败。缩合单宁是一类植物来源的多酚类物质，具有优良的加工特性和宝贵的生物学特性。细胞对含有商业上可获得的两性胺化缩合单宁的材料的反应已被报道。这项工作假设缩合单宁的化学成分可以被修饰，以调节对缩合单宁材料的重要生物反应。这项工作的目的是(I)通过化学修饰来改变其酸性、碱性和抗氧化活性；(Ii)利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；以及(Iii)利用化学修饰来调节与骨愈合相关的间充质干细胞分化和矿化。含有新的缩合单宁衍生物的表面的结果将与聚多巴胺(一种生物聚合物，其化学性质类似于单氟氯酚)、低聚乙二醇表面(存在氢键受体，但没有酸性或碱性基团)以及骨组织工程中常用的其他材料进行比较。这项拟议的工作将产生三种新的缩合单宁衍生物，含有增加的(酚醛)酸度、增加的(季胺)碱性或增加的醚(邻甲醚)官能团，具有良好的聚电解质行为、抗氧化活性和降解动力学。这项工作将阐明结构-性质关系，展示如何改变缩合单宁化学以调节蛋白质结合、巨噬细胞极化、吞噬、异物巨细胞形成和抗菌活性。这项工作还将证明缩合单宁的化学作用可以调节干细胞分化和表面矿化。这项工作将扩大本科生和硕士学生对研究计划的参与。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。