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.

医疗植入物主要由合成聚合物和金属组成，包括用于打开病变动脉的支架、恢复四肢和关节功能的整形植入物、帮助管理糖尿病的植入性血糖传感器以及许多其他设备。当这些物质被引入体内时，往往会产生负面的生物反应。许多植入物因不良的血液-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会导致心脏病发作和中风。植入物周围的慢性炎症会导致无法愈合的伤口，并降低传感器的性能。植入物表面的细菌感染可能非常难以治疗。患者可以使用药物来降低这些风险(如抗凝剂、消炎药和抗生素)，但这些药物可能会产生长期的副作用。应该通过开发在生物环境中具有更有利的相互作用的新材料来解决血液反应、炎症和感染，而不是用药物治疗患者。这项研究受到生物学的启发，旨在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，都会产生以糖为基础的天然聚合物，称为多糖。一些多糖为组织提供结构支持，而另一些多糖控制重要的生化过程或显示出抗菌和抗真菌活性，保护组织免受有害感染。这些多糖是在活组织中以纳米级组织起来的。藻类产生一种叫做卡拉胶的多糖，这种多糖在食品、化妆品和保健品中有商业用途。这项研究项目将开发具有化学和纳米级特征的改性卡拉胶，专门设计用于减少炎症、调节血液凝结和增强抗菌活性。使用卡拉胶，而不是合成聚合物或动物组织中的多糖，将为具有内在抗炎和抗菌活性的植入材料提供可持续的来源，改善患者的预后。这项研究将与拉丁美洲的专家合作进行，并纳入面向贫困社区青年和普通公众的外联活动。肝素是从动物组织中提取出来的，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，在组织工程中引起了极大的兴趣。合成的磺化/磺化聚合物(如聚苯磺酸盐、葡聚糖硫酸盐)也被建议作为新的生物材料；然而，它们需要使用苛刻和有毒的硫化化学物质。卡拉胶是一种天然的硫酸化多糖，商业上用于食品、化妆品和医药用途。它们是哺乳动物糖胺聚糖的潜在替代品。然而，它们的化学修饰和加工成纳米材料用于生物医学应用在现有文献中还没有被探索过。这项研究将产生一个化学修饰的卡拉胶文库，以(I)使它们能够组装到纳米材料表面，(Ii)调节表面的蛋白质结合和细胞炎症，(Iii)增强血液相容性，以及(Iv)引入抗菌活性。这项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，这些材料将被开发成具有免疫教育特性的材料。这项工作涉及来自拉丁美洲一个合作者实验室的博士生，并将包括通过新的项目来接触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。