SBIR Phase I: Virucidal surface coatings for prevention of COVID-19 transmission

这一小型企业创新研究（SBIR）第一阶段项目的更广泛影响/商业潜力将来自于降低COVID-19的总体死亡率，并降低插管患者的继发性感染（如呼吸机获得性肺炎（VAP））的发生率。2017年，抗菌/抗菌留置气管导管（ETT）市场估计为18.5亿美元，年增长率为6.6%，由于COVID-19和其他呼吸道疾病的爆发，可能会进一步增长。 超过50%的COVID-19死亡可归因于继发性医疗获得性感染（如VAP）引起的急性呼吸窘迫综合征（ARDS）。不幸的是，用于通风的ETT不能防止细菌在其表面上沉积（生物污垢）。 到目前为止，只有一种FDA批准的抗菌ETT没有将污垢作为VAP的根本原因，这一关键问题尚未解决。 该技术推进了具有新型涂层的ETT的开发，并可能用于其他留置生物医学医疗器械，包括导尿管、中心静脉导管和血液透析导管（预计市场规模：到2026年为777亿美元）。该技术将感染率降低约10%，可预防170万例医疗获得性感染，每年可挽救99，000人的生命，并在美国节省280 - 450亿美元的相关成本。该技术还将支持抗菌剂与表面相互作用的研究。SBIR第一阶段项目旨在确定在ETT上使用双子表面活性剂涂层的可行性，以降低COVID-19死亡率。目前防止ETT中生物结垢的方法包括掺入杀生物Ag+离子或将类似于传统表面活性剂的亲水性聚合物沉积到表面。 然而，这样的杀生物剂释放涂层释放具有细胞毒性和基因毒性的Ag+离子，并且活性剂逐渐耗尽。 同时，聚合物受到其主链中固有的疏水区域和常规“母体”表面活性剂的低表面活性的限制。 该项目将推进一类新型表面活性剂的开发，其结合了强大的双子表面活性剂的结构元素，其表面活性比传统的同类产品高出几个数量级，并具有分子精确和耐用的硅烷化表面改性技术。 通过模仿双子表面活性剂的结构，通过硅烷化将多个离子“头”基团引入涂层，亲水性和抗菌/抗微生物性能相对于传统的防污涂层将大大增加。该奖项反映了NSF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。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project will result from reducing overall COVID-19 mortality, and reducing the incidence of morbid secondary infections in intubated patients such as ventilator-acquired pneumonia (VAP). The market for antifouling/antimicrobial indwelling endotracheal tubes (ETTs) was estimated at $1.85 billion in 2017 with 6.6% annual growth, and further increases are likely due to the outbreaks of COVID-19 and other respiratory diseases. More than 50% of COVID-19 deaths are attributable to acute respiratory distress syndrome (ARDS) from secondary healthcare-acquired infections, such as VAP. Unfortunately, ETTs used for ventilation do not prevent bacterial settlement upon their surfaces (biofouling). To date there is only one FDA-approved antimicrobial ETT that does not target fouling as the root cause of VAP, leaving this critical issue unaddressed. The proposed technology advances the development of ETTs with novel coatings and can potentially be used in other indwelling biomedical medical devices, including urinary-, central venous-, and hemodialysis catheters (estimated market size: $77.7 billion by 2026). A ~10% reduction infection rate with this technology could prevent 1.7 million healthcare-acquired infections, annually saving 99,000 lives and $28-45 billion associated-cost in the US. This technology will also support research in antimicrobial interactions with surfaces. This SBIR Phase I project proposes to establish the feasibility of gemini-surfactant inspired coatings on ETTs to reduce COVID-19 mortality. Current approaches to prevent biofouling in ETTs involve incorporation of biocidal Ag+ ions or deposition of hydrophilic polymers resembling traditional surfactants to the surface. However, such biocide-release coatings liberate Ag+ ions that are cyto- and genotoxic and are subject to gradual depletion of the active agent. Meanwhile, the polymers are limited by both intrinsically hydrophobic regions in their backbones and the low surface activities of conventional “parent” surfactants. This project will advance the development of a new class of antifouling coatings combining structural elements of powerful gemini surfactants displaying surface activities orders of magnitude higher than their conventional counterparts, with the molecularly precise and durable surface modification technique of silanization. By mimicking the structures of gemini surfactants, incorporating multiple ionic “head” groups into the coating via silanization, hydrophilicity and antifouling/antimicrobial properties will be greatly increased relative to conventional antifouling coatings.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.