ACatechol receives NSF Grant in the fight against COVID-19

>50% of COVID-19 deaths are attributable to acute respiratory distress syndrome (ARDS) from secondary healthcare-acquired infections such as ventilator-associated pneumonia (VAP) as indwelling catheters, i.e., endotracheal tubes, used for ventilation possess no evolved host-defense mechanisms to prevent bacterial settlement upon their surfaces (biofouling).  ACatechol has developed a new class of innovative antifouling coatings by integrating the surface modification technique of silanization with powerful gemini-surfactant technology, which in pilot studies displays high levels of both hydrophilicity and resistance to bacterial colonization.  This technology is well poised to endow catheters with unmatched antifouling properties and may clinically reduce the incidence of morbid secondary infections in intubated patients, preventing ARDS, and reducing overall COVID-19 mortality.  This project will establish the feasibility of ACatechol’s gemini-surfactant inspired coatings on catheters to resist fouling from clinically relevant pathogens (P. aeruginosa, S. aureus) by identifying optimal coating methods, superhydrophilic homologs, and evaluating biofouling resistance.

Antifouling performance is directly correlated with the interfacial physical properties; predominantly hydrophilicity, but charge density and uniformity of the surface are additional important considerations.  We have identified structural homologs that are superhydrophilic, highly charged, and give molecularly uniform surfaces. Currently, we are systematically varying coating methods, and molecular structures, expanding our library of coating molecules through targeted synthesis to uncover key structure-activity relationships.  We have also demonstrated antifouling resistance under clinically relevant conditions in vitro.  Antifouling performance has been measured by biofilm assays, and we have accomplished the Milestone of <1% coverage of biofilm and >100% reduction in fouling relative to state-of-the-art catheters. 

State-of-the-art approaches to prevent biofouling in catheters 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 which are cyto- and genotoxic, and are subject to gradual depletion of the active agent, selecting for resistant strains.  Meanwhile, the antifouling activity of hydrophilic polymers is limited by both intrinsically hydrophobic regions in the polymer backbone and the hydrophilicity of their conventional “parent” surfactants.  To meet these challenges, ACatechol has developed a new class of antifouling coatings for biomedical device surfaces that combine structural elements of powerful gemini surfactants, displaying surface activities often 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 antimicrobial properties will be greatly increased relative to conventional antifouling coatings. 

The market for antifouling/antimicrobial catheters was valued at $45 billion in 2020 with 6.4% annual growth. To date, there is only one FDA-approved antimicrobial ETT (Bactigard®) which does not target fouling as the root cause of VAP, thus ETTs with our novel coatings may compete favorably.  This technology can also be applied to other indwelling biomedical medical devices including intravenous, urinary-, central venous-, and hemodialysis catheters (estimated market size: $77.7 billion by 2026). By demonstrating a reduction in infection rates of even only a few percent, the economics of scale still favor widespread adoption of this technology. Moreover, by uncovering how coating molecular structure, interfacial properties and antifouling performance are correlated, this research will enable significant progress in the field of interfacial/surface science.