SBIR-STTR Award

Direct to Phase II

The entire Research Plan contains proprietary/privileged information that Imbed Biosciences requests not be released to personsoutside the Government, except for purposes of review and evaluation.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 surfacesand debridement can be challenging, leaving biofilm fragments that remain resistant to antimicrobial therapy andact as a nidus for recrudescence of biofilms. There is no commercially available topical formulation effective indispersal 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® Matrixis a 20-25 µm-thick bioresorbable polymeric multilayer film that allows painless placement in wounds and canbe engineered to dissolve over several days. The ultrathin matrix conforms intimately to the underlying contoursof a wound bed to provide localized and long-term release of bioactive molecules. Imbed recently obtained FDAclearance for Microlyte® Ag wound matrix based on that platform, where the matrix was impregnated with silvernanoparticles formed in situ. It has been used successfully to heal chronic wounds in thousands of patients inU.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 synergyof silver and gallium (Ga3+) ions in eliminating biofilms. Based on those scientific findings and successful clinicaladoption of Microlyte® Ag matrix ultrathin form factor in hospitals, objective of this SBIR project is to develop aneconomic, easy to place, dissolvable wound contact matrix that can deploy synergy of silver and gallium on awound surface to eliminate biofilms. Year 1 of Phase 2 research identified 10 µg/cm2 silver nanoparticles and140 or 210 µg/cm2 gallium as optimal biocompatible loadings for Microlyte Matrix and showed that theseprototypes- (1) provided > 4 log10 CFU reduction in 48 h old mature biofilms of P. aeruginosa in vitro and > 3log10 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 biofilmbacteria by presenting them in a microscale matrix. Completion of Phase II research in Year 2 will result infinalizing one a biocompatible prototype that is effective in killing multispecies biofilm in porcine wound modelsand accelerate healing. Based on our FDA pre-sub meeting, this CRP research proposal aims to establish qualitycontrols, validate the product design, fabrication process, set up e-beam sterilization protocol and collect GLPpreclinical performance data on product manufactured under quality control, for accelerate an FDA 510k de Novoapplication. For this project, Imbed has assembled a team of researchers with substantial expertise inbiomaterials (Agarwal, Pranami, Dalsin, and Abbott), microbiology (Czuprynski), animal wound models(McAnulty) and clinical wound care (McAnulty and Schurr).

Public Health Relevance Statement:
NARRATIVE 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 recrudence 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.

Project Terms:
Adoption ; Animals ; Antibiotics ; Antibiotic Agents ; Antibiotic Drugs ; Miscellaneous Antibiotic ; Bacteria ; Biocompatible Materials ; Biomaterials ; biological material ; Biological Sciences ; Biologic Sciences ; Bioscience ; Life Sciences ; Debridement ; Sterile coverings ; Dressing ; Economics ; Engineering ; Gallium ; Ga element ; Government ; Hospitals ; In Vitro ; Investments ; Ions ; Length of Stay ; Number of Days in Hospital ; hospital days ; hospital length of stay ; hospital stay ; Microbiology ; Mus ; Mice ; Mice Mammals ; Murine ; Persons ; United States National Institutes of Health ; NIH ; National Institutes of Health ; Discipline of Nursing ; Nursing ; Nursing Field ; Nursing Profession ; Pain ; Painful ; Patients ; PF4 Gene ; Antiheparin Factor ; Blood Platelet Factor IV ; Blood platelet factor 4 ; Chemokine (C-X-C motif) Ligand 4 ; Factor 4 ; Heparin Neutralizing Protein ; Platelet Factor 4 ; Recombinant Platelet Factor 4 ; SCYB4 ; Small Inducible Cytokine B4 ; Small Inducible Cytokine Subfamily B, Member 4 ; gamma-Thromboglobulin ; platelet factor IV ; Polymers ; Privatization ; Pseudomonas aeruginosa ; P aeruginosa ; P. aeruginosa ; Pseudomonas pyocyanea ; Publications ; Scientific Publication ; Publishing ; Quality Control ; Rattus ; Common Rat Strains ; Rat ; Rats Mammals ; Research ; Research Personnel ; Investigators ; Researchers ; Research Proposals ; Safety ; Silver ; Ag element ; Family suidae ; Pigs ; Suidae ; Swine ; porcine ; suid ; Time ; Tissues ; Body Tissues ; Work ; wound healing ; Wound Repair ; wound resolution ; Wound Infection ; infected wound ; Microbial Biofilms ; biofilm ; Health Care Costs ; Health Costs ; Healthcare Costs ; Film ; Healthcare ; health care ; Recrudescences ; Treatment Cost ; Guidelines ; base ; improved ; Surface ; Chronic ; Clinical ; Phase ; Evaluation ; Oral cavity ; Buccal Cavity ; Buccal Cavity Head and Neck ; Cavitas Oris ; Mouth ; Painless ; non-painful ; nonpainful ; not painful ; Funding ; Life ; fighting ; Frequencies ; Complex ; Protocol ; Protocols documentation ; In Situ ; Source ; Operative Procedures ; Surgical ; Surgical Interventions ; Surgical Procedure ; surgery ; Operative Surgical Procedures ; meetings ; biocompatibility ; biomaterial compatibility ; experience ; Performance ; physical property ; bioresorbable polymer ; degradable polymer ; biodegradable polymer ; synergism ; microbial ; Devices ; Thickness ; Thick ; Effectiveness ; Antimicrobial resistant ; Resistance to antimicrobial ; anti-microbial resistance ; anti-microbial resistant ; resistance to anti-microbial ; resistant to anti-microbial ; resistant to antimicrobial ; Antimicrobial Resistance ; Data ; Reproducibility ; in vivo ; Small Business Innovation Research Grant ; SBIR ; Small Business Innovation Research ; Validation ; Preparation ; Process ; Development ; developmental ; pre-clinical ; preclinical ; healing ; design ; designing ; nanoparticle ; nano particle ; nano-sized particle ; nanosized particle ; Treatment Efficacy ; intervention efficacy ; therapeutic efficacy ; therapy efficacy ; wound ; tissue wound ; wounding ; wounds ; Resistance ; resistant ; antimicrobial ; anti-microbial ; prototype ; standard of care ; Topical Antibiotic ; topical anti-microbial ; topical antimicrobial ; Sterilization ; chronic wound ; chronic skin wound ; Formulation ; systemic toxicity ; wound closure ; skin wound ; cutaneous wound ; dermal wound ; polymicrobial biofilm ; mixed species biofilm ; multi-microorganism biofilm ; multispecies biofilm ; wound care ; wound assessment ; wound monitoring ; wound treatment ; treat wound ; wound management ; wound therapeutics ; wound therapy ; effectiveness validation ; validate effectiveness ; wound biofilm ; wound bed ; burn wound ; Impaired healing ; Healing abnormal ; Healing delayed ; Wound models ; wound healing models ;