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

医疗植入物，包括用于打开病变动脉的支架，恢复四肢和关节功能的矫形植入物，帮助控制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。当这些物质被引入人体时，通常会发生负面的生物反应。许多植入物由于不利的血液物质相互作用、炎症和感染而失败。心血管植入物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，降低传感器的性能。种植体表面的细菌感染非常难以治疗。患者可以通过药物治疗来降低这些风险（如抗凝血剂、消炎药和抗生素），但这些药物可能有长期副作用。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，而不是用药物治疗患者。本研究受生物学启发，开发生物医学植入物的新材料。包括动物、植物、真菌、藻类和细菌在内的生物体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，而其他多糖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。藻类产生一种被称为角叉菜胶的多糖，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。与从动物组织中合成聚合物或多糖相比，卡拉胶的使用将为具有固有抗炎和抗菌活性的植入材料提供可持续的来源，从而改善患者的预后。这项研究将与来自拉丁美洲的专家合作进行，并将纳入向贫困社区的青年和一般公众进行的外联活动。肝素从动物组织中提取，临床上用作抗凝血剂。肝素和其他磺化糖胺聚糖，如硫酸软骨素，因其稳定生长因子和增强其他生化功能的能力而在组织工程领域引起了极大的兴趣。合成磺化/磺化聚合物（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化化学物质。卡拉胶是天然硫酸酸化多糖，商业生产用于食品，化妆品和制药用途。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生物医学应用的纳米材料在现有文献中尚未被探索。这项研究将产生一个化学修饰的卡拉胶文库，以(i)使其能够组装到纳米结构材料表面，（ii）调节表面的蛋白质结合和细胞炎症，（iii）增强血液相容性，（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，这些材料将被开发成具有免疫指导特性的材料。这项工作涉及来自拉丁美洲合作者实验室的博士生，并将包括在丹佛大都会区最近开放的面向公众的校园中开展新项目，以吸引服务不足的社区。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.