Modified carrageenan-based nanomaterials as sustainable, immunomodulatory, hemocompatible, and antibactieral biomaterials

改性卡拉胶纳米材料作为可持续、免疫调节、血液相容性和抗菌生物材料

• 批准号: 2313878
• 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: Continuing 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=2313878&HistoricalAwards=false
• 关键词: Modified; carrageenan; based; nanomaterials; sustainable

Medical implants, including stents used to open diseased arteries, orthopedic implants that restore the use of limbs and joints, implanted blood glucose sensors that help manage diabetes, and many other devices, are primarily composed of synthetic polymers and metals. Negative biological responses often occur when these materials are introduced into the body. Many implants fail due to unfavorable blood-material interactions, inflammation, and infection. Blood clotting on cardiovascular implants can lead to heart attacks and strokes. Chronic inflammation around implants can cause non-healing wounds and degrade sensor performance. Bacterial infection on implant surfaces can be exceedingly difficult to treat. Patients can be treated with drugs to reduce these risks (such as anticoagulants, anti-inflammatories, and antibiotics), but these may have long-term side effects. Instead of treating patients with drugs, blood reactions, inflammation, and infection should be addressed by developing new materials that have more favorable interactions in the biological environment. This research is inspired by biology to develop new materials for biomedical implants. Living organisms, including animals, plants, fungi, algae, and bacteria all produce sugar-based, natural polymers called polysaccharides. Some polysaccharides provide structural support for tissues, while other polysaccharides govern important biochemical processes or exhibit antibacterial and antifungal activity, protecting tissues from harmful infections. These polysaccharides are organized at the nanoscale in living tissues. Algae produce a class of polysaccharides called carrageenans that are used commercially in food, cosmetics, and health care products. This research project will develop modified carrageenans with chemical and nanoscale features specifically designed to reduce inflammation, modulate blood clotting, and enhance antimicrobial activity. The use of carrageenans, as opposed to synthetic polymers or polysaccharides from animal tissues, will provide a sustainable source for implant materials with inherent anti-inflammatory and antimicrobial activity, improving outcomes for patients. The research will be conducted in collaboration with experts from Latin America and is integrated into outreach activities to youth and the general public in underprivileged communities. Heparin is harvested from animal tissues and used clinically as an anticoagulant. Heparin and other sulfated glycosaminoglycans, such as chondroitin sulfate, have generated significant interest in tissue engineering for their ability to stabilize growth factors and potentiate other biochemical functions. Synthetically sulfated/sulfonated polymers (e.g., polystyrene sulfonate, dextran sulfate) have also been proposed as new biomaterials; however, they require the use of harsh and toxic sulfation chemistries. Carrageenans are naturally sulfated polysaccharides, commercially produced for food, cosmetic, and pharmaceutical uses. They are potential alternatives to mammalian glycosaminoglycans. However, their chemical modification and processing into nanomaterials for biomedical applications is unexplored in the existing literature. This research will produce a library of chemically modified carrageenans to (i) enable their assembly into nanostructured materials surfaces, (ii) modulate protein binding and cellular inflammation on surfaces, (iii) enhance blood compatibility, and (iv) introduce antibacterial activity. The research is designed to elucidate structure-property-function relationships of this important class of renewable nano-biomaterials that will be developed to have immune-instructive properties. The work involves PhD students from a collaborator’s laboratory in Latin America and will include outreach with new programming to engage underserved communities at a public-facing campus recently opened in the Denver metropolitan area.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.

医疗植入物，包括用于打开患病动脉的支架，恢复肢体和关节使用的矫形植入物，帮助管理糖尿病的植入血糖传感器以及许多其他设备，主要由合成聚合物和金属组成。当这些物质被引入体内时，通常会发生负面的生物反应。许多植入物由于不利的血液材料相互作用、炎症和感染而失败。心血管植入物上的血液凝结可能导致心脏病发作和中风。植入物周围的慢性炎症可能导致伤口无法愈合，并降低传感器性能。种植体表面的细菌感染非常难以治疗。患者可以使用药物（如抗凝剂、抗炎药和抗生素）来降低这些风险，但这些药物可能会产生长期副作用。而不是用药物治疗患者，血液反应，炎症和感染应该通过开发在生物环境中具有更有利相互作用的新材料来解决。这项研究受到生物学的启发，开发用于生物医学植入物的新材料。生物体，包括动物、植物、真菌、藻类和细菌，都产生糖基的天然聚合物，称为多糖。一些多糖为组织提供结构支持，而其他多糖则控制重要的生化过程或表现出抗菌和抗真菌活性，保护组织免受有害感染。这些多糖在活组织中以纳米级组织。藻类产生一类称为角叉菜胶的多糖，其在商业上用于食品、化妆品和保健产品。该研究项目将开发具有化学和纳米级特征的改性角叉菜胶，专门用于减少炎症，调节血液凝固和增强抗菌活性。与来自动物组织的合成聚合物或多糖相反，角叉菜胶的使用将为具有固有抗炎和抗微生物活性的植入材料提供可持续的来源，从而改善患者的结局。这项研究将与拉丁美洲的专家合作进行，并将纳入针对贫困社区青年和公众的外联活动。肝素是从动物组织中获得的，临床上用作抗凝剂。肝素和其他硫酸化糖胺聚糖，如硫酸软骨素，由于其稳定生长因子和增强其他生化功能的能力，在组织工程中产生了重大的兴趣。合成硫酸化/磺化聚合物（例如，聚苯乙烯磺酸盐、硫酸葡聚糖）也被提议作为新的生物材料;然而，它们需要使用苛刻和有毒的硫酸化化学品。卡拉胶是天然硫酸化多糖，商业生产用于食品、化妆品和药物用途。它们是哺乳动物糖胺聚糖的潜在替代品。然而，它们的化学改性和加工成纳米材料用于生物医学应用是在现有的文献中未探索的。这项研究将产生一个化学改性角叉菜胶库，以（i）使其组装成纳米结构材料表面，（ii）调节表面上的蛋白质结合和细胞炎症，（iii）增强血液相容性，（iv）引入抗菌活性。该研究旨在阐明这类重要的可再生纳米生物材料的结构-性能-功能关系，这些材料将被开发为具有免疫指导性能。这项工作涉及来自拉丁美洲合作者实验室的博士生，并将包括新的项目推广，以吸引丹佛大都市区最近开放的面向公众的校园中服务不足的社区。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的影响审查标准进行评估来支持。