SBIR Phase I: Tunable Mechanical and Functional Properties of Peptide Films

SBIR 第一阶段：肽膜可调节的机械和功能特性

• 批准号: 1843682
• 负责人: Manav Mehta
• 金额: $ 22.5万
• 依托单位: Gel4Med
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2022-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1843682&HistoricalAwards=false
• 关键词: SBIR; Phase; Tunable; Mechanical; Functional

This SBIR Phase I project focuses on developing chemically cross-linked synthetic nanomaterials to address the unmet clinical need in promoting infection free tissue regeneration in surgical, traumatic, ocular, burn, and chronic wounds. While small wounds heal naturally, larger chronic wounds demonstrate delayed wound healing with infections, and affect over 6.5 million patients costing over US $25 billion annually in treatments. In addition, annually, 2 million Americans suffer from serious infections due to drug resistant bacteria resulting in severe morbidity, serious complications, huge economic losses with an estimated 23,000 deaths. As conventional antibiotics are failing, our ability to fight drug resistant pathogens is diminishing and the pipeline of new potential antibiotic drugs is very skim. Thus, there is an urgent need to develop a product that can fight multiple pathogens through a mechanism against which bacteria are less likely to develop further resistance. Hence, the current project evaluates the feasibility of developing a novel, easily handleable dry film with potential to eliminate a variety of infectious pathogens while improving wound healing in a single application. This product is pliable, easily rehydratable, has intrinsic tissue scaffolding properties and is inherently antimicrobial against a broad range of pathogens without the use of any additional agents. This SBIR Phase I project will demonstrate the feasibility of developing a shape retaining, pliable, easily handleable antimicrobial cell-scaffolding gel matrix into a product that is simultaneously toxic to antibiotic-resistant bacterial strains, while remaining conducive to tissue regeneration. This current product has a nano-porous gel matrix that promotes cellular infiltration and attachment along with utilizing a charge-based mechanism to lyse bacterial membranes upon contact. Although there is on-going research on such self-assembled hydrogels, the formation of films using these nanofibers has never been assessed before and stands to be the key technological advancement. Thus, this current proposal explores two methods for making films such as i) solvent casting methods relying on non-covalent crosslinking - where the hydrogel is applied to a surface and then allowed to dry into a film overnight, and ii) Covalent crosslinking by - incorporating cysteines by oxidizing using H2O2 or crosslinking using Schiff base formation followed by reductive deamination. The films so formed will be structurally and functionally evaluated for their ability to eliminate infections and biocompatibility.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.

该SBIR I期项目的重点是开发化学交联的合成纳米材料，以满足促进手术，创伤性，眼部，烧伤和慢性伤口的无感染组织再生的未满足临床需求。虽然小伤口自然愈合，但较大的慢性伤口表现出感染延迟的伤口愈合，每年在治疗中影响超过250亿美元的650万患者。此外，每年有200万美国人因耐药细菌而严重感染，导致严重的发病率，严重的并发症，巨大的经济损失，估计有23,000人死亡。由于常规的抗生素失败，我们与抗药性病原体作斗争的能力正在减少，而新的潜在抗生素药物的管道非常略高。因此，迫切需要开发一种可以通过一种机制来抵抗多种病原体的产品，而细菌不太可能发展出进一步的抗性。因此，当前的项目评估了开发一种新型，易于可交换的干膜的可行性，并有可能消除各种感染性病原体，同时在单个应用中改善伤口愈合。该产品具有柔韧性，容易补充水化，具有内在的组织脚手架特性，并且本质上是针对广泛的病原体的抗菌剂，而无需使用任何其他药物。 该SBIR I期项目将证明开发形状保留，柔韧，易于可交换的抗菌细胞脱落的凝胶矩阵，与抗生素耐药细菌菌株有毒的产品，同时使组织再生有毒性。该电流产物具有纳米孔凝胶基质，可促进细胞浸润和附着，并在接触后利用基于电荷的机制裂解细菌膜。尽管对这种自组装水凝胶进行了正在进行的研究，但使用这些纳米纤维的膜形成以前从未被评估过，并且是关键的技术进步。因此，该当前的提案探讨了制作薄膜的两种方法，例如i）依赖于非共价交联的溶剂铸造方法 - 将水凝胶应用于表面上，然后允许将膜变干成薄膜过夜，ii）通过使用H2O2或Crossine crodive condife condive inford condife infort infactive infodeative contife contife contife contife contife contive in crodive infor schiff inflactive infor -nightife。如此形成的电影将在结构和功能上评估其消除感染和生物相容性的能力。该奖项反映了NSF的法定任务，并且使用基金会的知识分子优点和更广泛的影响审查标准，被认为值得通过评估来获得支持。