SBIR-STTR Award

The health care burden associated with treatment of chronic and burn wounds amounts to more than $25 billion annually in the U.S., involving 8.6 million patients. One recent advance in wound care has been the development of "biologic dressings" that contain animal-derived components such as collagen. Biologic dressings provide superior healing rates in burns and chronic wounds. Associated with their use, however, is a significant rate (up to 20%) of bacterial infection that results in increased healing time, patient pain, and treatment costs. Therefore, an unmet need with the potential to broadly advance wound care is the fabrication of biologic dressings that incorporate broad-spectrum antibacterial agents such as silver. Silver formulations are widely used in hospitals for treatment of wound infections. However, approaches used to incorporate stabilized forms of silver into conventional dressings cannot be adapted to biologic dressings because the chemical and physical processing involved compromises their structure and activity. To address these needs, Imbed Biosciences, Inc. is developing a platform technology that enables integration of molecularly-thin polymer films containing precise loadings of bioactive agents onto wound dressings and skin substitutes. In this Phase 1 proposal, Imbed will optimize this technology to integrate silver nanoparticles onto biologic wound dressings (the exemplar of which will be Biobrane(R), a leading biologic dressing) such that they inhibit bacterial colonization without compromising cellular growth and repair. The innovation in Imbed's approach includes: (i) the engineering of nanometer-thick polymer films impregnated with precise loadings of silver nanoparticles that exert antimicrobial activity without cytotoxicity; and (ii) transfer of polymer films containing silver nanoparticles onto biologic dressings without compromising their structure and bioactivity. Preliminary data shows that Imbed's silver nanoparticle-coating that releases concentrations of silver two orders of magnitude lower than those released from conventional silver dressings, when integrated on Biobrane(R), killed 99.9999% bacteria (6 log10) on its surface within 24 hr and prevented sepsis in experimentally infected wounds in mice. For this project, Imbed has assembled a highly accomplished team of researchers with substantial expertise in biomaterials (Agarwal and Abbott), microbiology (Czuprynski), animal wound models (McAnulty and Murphy) and clinical wound care (McAnulty, Murphy and Schurr). In this proposal, polymer films containing silver nanoparticles will be integrated on Biobrane(R). In Aim 1, silver loadings that lead to antimicrobial activity without cytotoxicity in in-vitro assays will be optimized. Aim 2 will provide safety and efficacy data in mice by identifying silver loadings that do not cause systemic toxicity, facilitate normal wound healing, and promote healing of model infected wounds. Completion of these aims will enable further commercialization discussions with customers and provide critical feasibility data for Phase 2 studies (to include a wider range of bacterial strains/wound models).

Public Health Relevance:
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 class of hybrid wound dressings that combine the benefits of biologic and antimicrobial wound dressings. The new wound dressings will expedite wound closure, reduce use of antibiotics, minimize dressing changes and nurse time, and lower patient pain, medication costs and length of hospital stays.

Public Health Relevance Statement:
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 class of hybrid wound dressings that combine the benefits of biologic and antimicrobial wound dressings. The new wound dressings will expedite wound closure, reduce use of antibiotics, minimize dressing changes and nurse time, and lower patient pain, medication costs and length of hospital stays.

Project Terms:
bacterial disease; Bacterial Infections; Cellular Growth; Cellular Expansion; cell growth; Bacteria; Burns; Burn injury; Biologic Assays; Bioassay; Assay; Biological Assay; biological material; Biomaterials; Biocompatible Materials; Beds; Biologic Dressing; Biological Dressings; Animals; Miscellaneous Antibiotic; Antibiotic Drugs; Antibiotic Agents; Antibiotics; Agar; painkiller; pain reliever; pain medication; pain killer; Antinociceptive Drugs; Antinociceptive Agents; Anodynes; Analgesic Preparation; Analgesic Drugs; Analgesic Agents; Analgesics; Engineering; Diffusion; Dressing; Sterile coverings; Collagen; clinical investigation; Clinical Trials; Painful; Pain; Nurses; Methods; Medical Device; Microbiology; heavy metal lead; heavy metal Pb; Pb element; Lead; In Vitro; hospital stay; hospital length of stay; hospital days; Number of Days in Hospital; Length of Stay; Infection; Hybrids; Modern Man; Man (Taxonomy); Human; Hospitals; Saline Solution; Saline; suid; S.aureus; S. aureus; Staphylococcus aureus; Technology; porcine; Swine; Suidae; Pigs; Family suidae; Safety; Researchers; Investigators; Research Personnel; Pseudomonas pyocyanea; P.aeruginosa; P. aeruginosa; Pseudomonas aeruginosa; Murine; Mice Mammals; Mice; Mus; Patents; Legal patent; Peptides; Patients; Polymers; Research; Clinical; antibiotic resistant; Resistant to antibiotics; Resistance to antibiotics; Antibiotic Resistance; Chronic; Caring; Generic Drugs; generic; Nonproprietary Drugs; Healed; repair; repaired; Phase; Film; Relative; Relative (related person); health care; Healthcare; base; Killings; Treatment Cost; Time; Ag element; Silver; Wound Repair; Wound Healing; Translations; Testing; Body Tissues; Tissues; Wound Infection; Clinic; mechanical; Mechanics; scaffolding; scaffold; antibacterial; anti-bacterial; Antibacterial Agents; Anti-Bacterial Agents; nano meter; nanometer; antimicrobial agent; anti-microbial drug; anti-microbial agent; antimicrobial drug; Dermal; Licensing; Surface; Chemicals; Area; Methicillin Resistant Staphylococcus Aureus; Methicillin Resistant S. Aureus; MRSA; methicillin resistant Staphylococcus aureus (organism); Modeling; resection; Surgical Removal; Removal; Extirpation; Abscission; Excision; Skin Substitutes; Thickness; Thick; healthcare economics; health care economics; Toxicities; Toxic effect; Structure; Performance; Lytotoxicity; cytotoxicity; Formulation; Drug Formulations; Physical Phenomena or Properties; physical process; wound cleaning; healing; bactericidal; bactericide; in vitro Assay; Molecular; cost; care burden; developmental; Development; preclinical; pre-clinical; Small Business Innovation Research; SBIRS (R43/44); SBIR; Small Business Innovation Research Grant; Process; regenerating damaged tissue; regenerate new tissue; tissue regeneration; Address; Manufacturer; Manufacturer Name; Data; preventing; prevent; commercialization; innovative; innovate; innovation; bloodstream infection; Sepsis; anti-microbial; antimicrobial; diabetes mouse model; Diabetic mouse; wound; nano particle; nanoparticle; phase II study; phase 2 study

Clinical infections in burn, trauma and surgical wounds represent a huge economic and health care burden. In the U.S., there is a 2-5% infection rate in surgical wounds and up to a 20% rate in burn wounds. The current standard of care is intensive and expensive, involving frequent topical application of antimicrobials (twice daily) with painful dressing changes. Expensive advanced dressings with antimicrobials impair wound healing by depositing toxic concentrations of antimicrobials (typically >100 μg/cm2 of silver/day). When used with biologic dressings, these standards of care still result in up to 20% infection rate. There is a critical unmet need for formulations that provide: long-term release of antimicrobials without toxic build up in wounds; support broad therapeutic use of advanced dressings; and reduce frequent dressing changes. Successful completion of Phase 1 research at Imbed Biosciences has resulted in the invention and development of a unique silver wound dressing product concept based on Imbed's patent-pending nanofilm technology: dissolvable microfilm wound contact dressing with uniquely stabilized silver nanoparticles. A key feature of the microfilm dressing is that it contains a small quantity of silver that provides more intimate contact of active silver with the wound bed, which is less toxic to the wound and gentler to use. The microfilm dressing conforms to the micro-contours of the wound bed to provide 'localized' and 'long-term' release of active silver ions. Inexpensive fabrication and low cost of goods makes the microfilm dressing a cost-efficient alternative (>60% savings) to expensive silver dressings for use with moist and biologic wound dressings. Results of Phase I research demonstrated that the microfilm silver dressing (1) kills 4 log10 CFU of several bacterial species, including MRSA, (2) provides sustained release of bactericidal silver for at least 4 days, (3) does not show detectable in-vitro cytotoxicity or in-vivo systemic toxicity, (4) allows normal wound healing by re-epithelialization, and (5) significantly reduces microbial colonization and expedites wound closure under biosynthetic dressings in contaminated murine wounds. Comparison to other silver dressings showed that the microfilm dressing releases up to 100x less silver than most available dressings, provides equivalent or better antibacterial activity, an allows normal wound re-epithelialization unlike some silver dressings. Based on this promising data from Phase 1 research, and enthusiastic feedback from clinicians and potential commercial partners, Phase II research aims to further develop, optimize, and validate the Microfilm Silver Dressing product concept for high-throughput fabrication (Aim 1), broad-spectrum antimicrobial activity (Aim 2), biocompatibility (Aim 3), and porcine wound healing (Aim 4). We have assembled a team of material scientists, microbiologists, and veterinary and medical surgeons, with a history of successful collaboration. Completion of Phase II research will provide optimized design and data sets for microfilm dressings required for manufacturing scale-up and regulatory approval for human clinical trials.

Public Health Relevance Statement:


Public Health Relevance:
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 unique microfilm wound dressing that immobilize broad- spectrum antibacterial agents on the wound surface and prevent wound infections under primary and secondary wound dressing. The new microfilm dressing will reduce frequent application of topical antiseptics and use of antibiotics; minimize painful dressing changes and nurse time, and lower patient pain, medication costs and length of hospital stays.

Project Terms:
painkiller; pain reliever; pain medication; pain killer; Antinociceptive Drugs; Antinociceptive Agents; Anodynes; Analgesic Preparation; Analgesic Drugs; Analgesic Agents; Analgesics; Anions; Miscellaneous Antibiotic; Antibiotic Drugs; Antibiotic Agents; Antibiotics; Beds; Biologic Dressing; Biological Dressings; Burns; Burn injury; 2,4,11,13-Tetraazatetradecanediimidamide, N,N''-bis(4-chlorophenyl)-3,12-diimino-; Chlorhexidine; clinical investigation; Clinical Trials; Death; Cessation of life; Dressing; Sterile coverings; Economics; Exudate; Feedback; Gel; Health; History; Recording of previous events; Modern Man; Man (Taxonomy); Human; In Vitro; Infection; Ions; heavy metal lead; heavy metal Pb; Pb element; Lead; hospital stay; hospital length of stay; hospital days; Number of Days in Hospital; Length of Stay; Marketing; Microfilming; Murine; Mice Mammals; Mice; Mus; Nurses; Unguents; Salves; Ointments; Painful; Pain; Patents; Legal patent; Patients; Polymers; gene product; Proteins; Research; Savings; Ag element; Silver; Solutions; Stains; suid; porcine; Swine; Suidae; Pigs; Family suidae; Technology; Time; Body Tissues; Tissues; Hydrogen Oxide; Water; Wound Repair; Wound Healing; Wound Infection; health care; Healthcare; Dataset; Data Set; Caring; Killings; base; improved; Surface; Clinical; Healed; Phase; Medical; Dermal; antibacterial; anti-bacterial; Antibacterial Agents; Anti-Bacterial Agents; Collaborations; Tissue Stains; Surgical wound; Deposit; Deposition; mechanical; Mechanics; Scientist; Frequency; Frequencies (time pattern); irritation; Stainings; Staining method; Formulation; Drug Formulations; microfiche; Microfilm; surgery; Surgical Procedure; Surgical Interventions; Surgical; Operative Procedures; Operative Surgical Procedures; Prevent infection; Infection prevention; Surgeon; biocompatibility; biomaterial compatibility; Lytotoxicity; cytotoxicity; microbial colonization; Toxicities; Toxic effect; healthcare economics; health care economics; topically applied; topical drug application; topical administration; Topical Drug Administration; Topical application; LOINC Axis 2 Property; Property; nanotech; nano technology; nano tech; nano scale Science; Nanoscale Science; Nanotechnology; Therapeutic Uses; Methicillin Resistant Staphylococcus Aureus; Methicillin Resistant S. Aureus; MRSA; methicillin resistant Staphylococcus aureus (organism); Thickness; Thick; preventing; prevent; cytotoxic; Data; in vivo; Small Business Innovation Research; SBIRS (R43/44); SBIR; Small Business Innovation Research Grant; translation research enterprise; translation research; Translational Science; Translational Research Enterprise; Translational Research; Molecular; Process; developmental; Development; regenerating damaged tissue; regenerate new tissue; tissue regeneration; bactericidal; bactericide; care burden; cost; healing; health economics; designing; design; bloodstream infection; Sepsis; topical antiseptic; nano particle; nanoparticle; wound; abnormal tissue repair; delayed wound healing; Impaired tissue repair; Impaired healing; Healing delayed; Healing abnormal; Impaired wound healing; pathogen; Trauma; anti-microbial; antimicrobial; Microbe; Burn Trauma; standard of care; manufacturing scale-up; topical antimicrobial; topical anti-microbial; Topical Antibiotic