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 ?m-thick dissolvable 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. Results of Phase 1 feasibility study documented that MicroLyte Matrix, when strategically impregnated with non-toxic loadings of silver nanoparticles and gallium in polymeric multilayers, is able to disperse >4 log10 CFUs of bacteria in a mixed species biofilm in vitro. In a delayed wound healing model in mice, such a matrix eliminated >90% of bacteria in a pre-established robust biofilm within 3 days of treatment. 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. Phase 1 results provide strong support for pursuing a Phase 2 study to optimize the MicroLyte Matrix design that can obtain faster elimination of biofilms in the wound bed. The goals of Phase 2 research are: (1) Tailor MicroLyte Matrix for higher loadings and extended release of silver and gallium, (2) Screen biocompatibility limits of silver and gallium in the matrix, (3) Screen dose response against mixed species biofilms in vitro, (4) Optimize loadings for dispersal of biofilms in a murine splinted-wound model, and (5) Evaluate effect on healing in a porcine wound model infected with biofilms. 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). Successful completion of Phase 2 research will result in a shelf-stable MicroLyte Ag/Ga matrix with safety and efficacy data that can be readily translated into human clinical studies for FDA clearance.
Wound management presents a huge economic and healthcare burden in the U.S. The research described in this SBIR application will lead to the realization of a new form factor for wound management: an ultrathin dissolvable matrix that synergistically combines the benefits of antimicrobial and antibiofilm agents to aid wound-bed preparation. The new wound matrix will adhere intimately to the contours of wound-bed, allow moist wound healing, and kill bacteria in biofilms hiding in crevices of wound tissue surface. It will reduce the frequency of surgical debridement in chronic wounds by eliminating fragments of biofilms harboring in wound-bed, the breaking the cycle of microbial recrudescence in chronic wounds. Adoption of this new antibiofilm matrix in work-flow of clinical wound management may expedite wound closure, reduce use of antibiotics, reduce nursing time, lower patient pain, reduce length of hospital stays, and reduce overall wound treatment costs.
