Condensed tannin polymers as a new functional biomaterials

点击翻译按钮获取中文摘要

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.