Ultrathin dissolvable antibiofilm wound contact dressing with silver and gallium

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The entire Research Plan contains proprietary/privileged information that Imbed Biosciences requests not be released to persons outside the Government, except for purposes of review and evaluation. SUMMARY The health care costs associated with treatment of chronic wounds exceeds $25 billion annually in the U.S. Biofilms are implicated as a key factor responsible for delayed healing. Many wounds have complex surfaces and debridement can be challenging, leaving biofilm fragments that remain resistant to antimicrobial therapy and act as a nidus for recrudescence of biofilms. There is no commercially available topical formulation effective in dispersal of biofilms in wounds. Research at Imbed Biosciences, funded by NIH and private equity investments, has resulted in the development of an ultrathin wound contact matrix with a unique form factor. Microlyte® Matrix is a 20-25 µm-thick bioresorbable polymeric multilayer film that allows painless placement in wounds and can be engineered to dissolve over several days. The ultrathin matrix conforms intimately to the underlying contours of a wound bed to provide localized and long-term release of bioactive molecules. Imbed recently obtained FDA clearance for Microlyte® Ag wound matrix based on that platform, where the matrix was impregnated with silver nanoparticles formed in situ. It has been used successfully to heal chronic wounds in thousands of patients in U.S. It is effective in killing a broad spectrum of bacteria in vitro and in infected wound models in mice. However, it is not effective in killing bacteria encased in biofilms. In our recently published study, we demonstrated synergy of silver and gallium (Ga3+) ions in eliminating biofilms. Based on those scientific findings and successful clinical adoption of Microlyte® Ag matrix ultrathin form factor in hospitals, objective of this SBIR project is to develop an economic, easy to place, dissolvable wound contact matrix that can deploy synergy of silver and gallium on a wound surface to eliminate biofilms. Year 1 of Phase 2 research identified 10 µg/cm2 silver nanoparticles and 140 or 210 µg/cm2 gallium as optimal biocompatible loadings for Microlyte Matrix and showed that these prototypes- (1) provided > 4 log10 CFU reduction in 48 h old mature biofilms of P. aeruginosa in vitro and > 3 log10 CFU reduction in a mice wound model, and (2) were biocompatible in accordance to ISO 10993 guidelines. These results proved our scientific premise of amplifying synergy in pairing gallium and silver ions against biofilm bacteria by presenting them in a microscale matrix. Completion of Phase II research in Year 2 will result in finalizing one a biocompatible prototype that is effective in killing multispecies biofilm in porcine wound models and accelerate healing. Based on our FDA pre-sub meeting, this CRP research proposal aims to establish quality controls, validate the product design, fabrication process, set up e-beam sterilization protocol and collect GLP preclinical performance data on product manufactured under quality control, for accelerate an FDA 510k de Novo application. For this project, Imbed has assembled a team of researchers with substantial expertise in biomaterials (Agarwal, Pranami, Dalsin, and Abbott), microbiology (Czuprynski), animal wound models (McAnulty) and clinical wound care (McAnulty and Schurr).