Surgical site infections (SSIs) are a leading complication of surgery. SSIs cause patient morbidity and mortality, and place a significant burden on healthcare. Despite high standards of preventive care, wound infections are a serious problem. Surgical incisions break host defense barriers and increase microbial contamination of tissues. Biocompatible antimicrobial barriers that can be applied directly in the wound of surgery could dramatically reduce infections. Amicrobe scientists, working in collaboration with Professor Timothy J. Deming (UCLA Bioengineering), are developing block copolypeptides that self-assemble into hierarchical structures to accomplish this objective. Amicrobe's lead product candidates are novel block copolypeptides that self-assemble into unique antimicrobial hydrogels. Notably, these physical hydrogels are not covalently cross-linked and, therefore, can flow upon (mild) deformation to fill wound cavities and rapidly re-gel. An advantage of our method is the ability to engineer chemical and physical characteristics (e.g. hierarchical structures) that may improve efficacy and safety. Preliminary data suggest that our lead hydrogels are broadly antimicrobial, effective in SSI models, and biocompatible with tissues. Our final product will be designed for ease of application, duration of antimicrobial activity, and support of wound healing. Direct application to wound cavities prior to surgical closure could significantly reduce the number of superficial and deep incisional SSIs and organ-space SSIs. Amicrobe's hydrogel product may also help prevent infections in traumatic wounds and chronic wounds such as diabetic foot ulcers. The goal of these Phase I studies is to select and formulate a lead product candidate for further development. Specifically, we are scaling up synthesis of three closely related candidates to enable critical studies in the selection process. Chemical properties will be analyzed, and physical properties will be assessed at multiple concentrations and formulations. Selected preparations will be tested in pilot studies of SSI models for prevention of wound infection. A lead compound will be chosen. It is anticipated that Phase II studies will focus on large-scale synthesis, additional SSI models, and toxicology.
Public Health Relevance: Surgical site infections (SSIs) cause patient morbidity and mortality, and place a significant burden on the healthcare system. Surgical incisions break host defense barriers and increase microbial contamination of tissues. To prevent infection, Amicrobe is developing a novel biocompatible hydrogel that would complement today's standards of care and provide antimicrobial barrier protection at the site of surgery. Amicrobe's unique product may also help prevent infections in traumatic wounds, as well as chronic wounds such as diabetic foot ulcers.
Public Health Relevance Statement: Surgical site infections (SSIs) cause patient morbidity and mortality, and place a significant burden on the healthcare system. Surgical incisions break host defense barriers and increase microbial contamination of tissues. To prevent infection, Amicrobe is developing a novel biocompatible hydrogel that would complement today's standards of care and provide antimicrobial barrier protection at the site of surgery. Amicrobe's unique product may also help prevent infections in traumatic wounds, as well as chronic wounds such as diabetic foot ulcers.
NIH Spending Category: Bioengineering; Infectious Diseases; Prevention
Project Terms: Amino Acids; antimicrobial; base; Binding (Molecular Function); Biocompatible; Biological; biomaterial compatibility; Biomedical Engineering; Caring; Characteristics; Chemical Engineering; chemical property; chemical synthesis; Chemicals; Chronic; Collaborations; Complement; Complication; cost; Cost Savings; crosslink; Data; design; Development; Diabetic Foot Ulcer; direct application; Drug Formulations; Engineering; Event; Family suidae; Foreign Bodies; Gel; Goals; Healed; healing; Healthcare; Healthcare Systems; high standard; Host Defense; Hydrogels; improved; in vivo; in vivo Model; Individual; Infection; Infection prevention; Inflammation; intermolecular interaction; Ionic Strengths; Ions; Kilogram; Lead; Length; Leucine; Liquid substance; Lysine; Methods; microbial; Modeling; Molecular Weight; Morbidity - disease rate; Mortality Vital Statistics; novel; open wound; Operative Surgical Procedures; Organ; Patients; Phase; phase 1 study; phase 2 study; Physical assessment; physical property; Pilot Projects; polypeptide; Preparation; Prevention; Preventive; Process; professor; Reporting; Reproducibility; Rheology; Rodent; Safety; scale up; Scientist; Selection Criteria; self assembly; Series; Serum; Site; Solutions; Sterility; Structure; Surgical incisions; Surgical Models; System; Testing; Time; Tissues; Toxicology; Translating; Trauma; van der Waals force; Work; wound; Wound Healing; Wound Infection
