Explore novel hydrogelable covalent conjugates of caprylic acid to amplify its bactericidal and pro-healing capability for accelerated healing of infected wounds

The National Institute of Allergy and Infectious Diseases awarded Louisiana State University Health Sciences Center New Orleans $225,000 on August 18, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to develop and evaluate hydrogel-forming covalent conjugates of caprylic acid as therapeutics for infected wounds.

The research aims to engineer self-assembling gel-forming conjugates that covalently link caprylic acid with tripeptides to overcome rapid clearance and provide tissue scaffolding. The conjugates are designed to kill bacteria within biofilms caused by Staphylococcus aureus and Pseudomonas aeruginosa, sustain caprylic acid release during biodegradation, and restore wound healing in diabetic infected wounds. Work encompasses two objectives: engineering and benchmarking wound-compatible conjugate gels to explore how chemical composition influences mechanical properties and cell compatibility, and evaluating therapeutic efficacy, biodegradation, caprylic acid release kinetics, and immunomodulation to identify the most effective formulations for amplifying caprylic acid's bactericidal and pro-healing functions.

The project is classified as a Project Grant, with performance at Louisiana State University Health Sciences Center New Orleans in New Orleans, Louisiana. The period of performance runs through July 31, 2028.

Abstract

Millions of americans suffer infected wounds (IWS), particularly diabetic IWS (diws), resulting in immense medical and economic burdens. Antimicrobial resistance has severely limited available treatments, with staphylococcus aureus (SA) and pseudomonas aeruginosa (PA) as predominant pathogens forming biofilms that hinder healing. Current therapies fail to eradicate biofilms or restore tissue repair. Our long-term goal is to develop therapeutics that both eliminate infection and RE-establish regeneration. Caprylic acid (C8), an eight- carbon fatty acid, exhibits strong bactericidal, immunomodulatory, and pro-healing properties but is rapidly cleared and unable to support tissue scaffolding. To overcome these limitations, we developed hydrogel- forming covalent C8-tripeptide conjugates (conjs). These self-assembling amphiphiles form tunable, shear- thinning gels that flow into irregular wound cavities, kill bacteria within biofilms, and sustain C8 release during biodegradation. Central hypothesis: self-assembling, GEL-forming conjs−covalently linking C8 with gelling- aid tripeptides−amplify C8's bactericidal, immunomodulatory, and pro-healing functions, eradicate biofilms, shifting wound immunity toward regeneration and resolution, and restore healing in diws. Objective: to explore tunable conj gels as novel multifunctional therapeutics that restore healing without the toxicity, tissue incompatibility, or limited efficacy of current single-function modalities. We propose two aims. Aim 1: engineer and benchmark wound-compatible conj gels; explore how GEL chemical composition influences mechanical properties and cytocompatibility. Aim 2: evaluate therapeutic efficacy, biodegradation/C8-release, and immunomodulation to identify the most effective conj gels for amplifying C8's bactericidal, immunomodulatory, and pro-healing properties in diws. A) test conj gels in vitro for mrsa and PA biofilm eradication. B) develop treatment regimens using the two lead conj gelators identified from our pilot study, aim 1, and aim 2A to eliminate mrsa/PA infection and restore healing in DB/DB diabetic mouse model. C) define GEL biodegradation and C8 release in wounds by LC-MS/MS. D) assess immunomodulation in human blood immunocytes and mouse diws, including potential shifts toward reparative immunity [↑ M2-like macrophages (MɸS) and regenerative pro-resolving factors, ↓ inflammatory factors/M1-like MɸS).overall impact: this R21 will 1) deliver novel self-assembling, GEL-forming conjs that amplify C8's bactericidal, immunomodulatory, and pro-healing functions to restore healing in infected diabetic wounds; 2) provide insights on chemical and mechanical parameters driving conj GEL efficacy; and 3) advance a new biomaterial platform that transforms short-lived bioactives into long-acting, multifunctional gels as therapeutics. The most effective conj gels have strong potential for translating into safer, more effective, and user-friendly therapeutics for infected diabetic wounds. Our team brings proven expertise in developing conj gels and evaluating their antibacterial and wound-healing properties.