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

该SBIR第一阶段项目专注于开发化学交联的合成纳米材料，以满足在促进外科、创伤、眼部、烧伤和慢性伤口无感染组织再生方面尚未满足的临床需求。虽然小伤口会自然愈合，但较大的慢性伤口会因感染而延迟愈合，并影响到650多万名患者，每年的治疗费用超过250亿美元。此外，每年有200万美国人受到抗药性细菌的严重感染，导致严重的发病率、严重的并发症和巨大的经济损失，估计有2.3万人死亡。随着传统抗生素的失效，我们对抗耐药病原体的能力正在减弱，潜在的新抗生素药物的流水线非常少。因此，迫切需要开发一种产品，通过一种细菌不太可能对其产生进一步耐药性的机制来对抗多种病原体。因此，目前的项目评估了开发一种新型的、易于操作的干膜的可行性，该干膜具有消除各种感染性病原体的潜力，同时在单一应用中改善伤口愈合。该产品柔韧，易于再水化，具有固有的组织支架特性，在不使用任何额外试剂的情况下，对多种病原体具有固有的抗菌作用。这个SBIR第一阶段项目将证明，将一种形状保持、柔韧、易于处理的抗菌细胞支架凝胶基质开发成对耐药细菌菌株同时具有毒性的产品的可行性，同时仍有利于组织再生。目前的产品具有纳米多孔凝胶基质，可促进细胞渗透和附着，并利用基于电荷的机制在接触时溶解细菌膜。尽管对这种自组装水凝胶的研究正在进行中，但使用这些纳米纤维形成薄膜的过程以前从未被评估过，而且将是关键的技术进步。因此，目前的建议探索了两种制备薄膜的方法，例如i)依赖于非共价交联的溶剂浇铸方法-将水凝胶涂在表面上，然后让其在夜间干燥成膜，以及ii)共价交联-通过使用双氧水氧化半胱氨酸或使用席夫碱形成的交联剂然后还原脱胺来结合半胱氨酸。这样形成的薄膜将从结构和功能上对其消除感染和生物兼容性的能力进行评估。该奖项反映了NSF的法定使命，并已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。

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.