Immunomodulation, drug delivery, and biomaterials for combating wound infection and promoting wound healing - absrtact despite efforts to maintain sterile operating rooms, surgical site infections…

The National Institute of General Medical Sciences awarded the Board of Regents of the University of Nebraska, through its University of Nebraska Medical Center division, $415,113 under the Biomedical Research and Research Training program (CFDA 93.859) on September 1, 2026.

The award funds development of nanofiber-based sutures and dressings to reduce surgical site infections, treat wound biofilms, and promote chronic wound healing. The research builds on prior findings demonstrating successful encapsulation and sustained release of vitamin D and other immunomodulating compounds to induce antimicrobial peptide expression, efficacy of Janus-type wound dressings in biofilm eradication, and effectiveness of three-dimensional nanofiber scaffolds with patterned macrochannels in wound repair and tissue regeneration, particularly in diabetic wound models when combined with W379 peptides.

Performance occurs in Omaha, Nebraska, with a period of performance through June 30, 2031. This is a Project Grant, a standard assistance type under the program.

Immunomodulation, drug delivery, and biomaterials for combating wound infection and promoting wound healing - absrtact despite efforts to maintain sterile operating rooms, surgical site infections (ssis) persist, causing up to 8,200 annual deaths in the united states. Chronic wound infections, especially in diabetic foot ulcers, pose a significant challenge, with over 90% exhibiting biofilm complexity. Diabetes affects 23.6 million americans, leading to foot ulceration in 20-25%, resulting in infections in 63.4%. Our long-term goal is to develop innovative therapies for reducing ssis, treating wound biofilms, and promoting chronic wound healing. In our previous studies, we demonstrated that i) successful encapsulation and sustained release of vitamin d and other immunomodulating compounds induced higher levels of cathelicidin antimicrobial peptide (camp) gene and protein (HCAP18/LL- 37) in various models; II) vitamin d-treated immune cells secreted exosomes with elevated HCAP18/LL-37 levels, III) janus-type wound dressings effectively deliver antimicrobial agents, eradicating biofilms both EX vivo and in vivo, IV) 3D nanofiber scaffolds, generated by using gas-foaming expansion technology, demonstrated efficacy in wound repair and tissue regeneration; v) 3D poly(ε-caprolactone) (PCL)/gelatin nanofiber aerogels with PAT- terned macrochannels and anisotropic microchannels were produced, significantly enhancing cellular infiltration rates and host tissue integration; and VI) nanofiber aerogels with a nanofibrous architecture, achieved through a process involving partially anisotropic freeze-drying, crosslinking, and sacrificial templating with 3D-bioprinted meshes, exhibit effective healing properties for diabetic wounds in mice, particularly with the addition of W379 peptides to precision macrochannels. Building on these findings, and our preliminary data, the goal of our pro- posal focuses on the development of nanofiber-based sutures and dressings for enhancement of innate immun- ITY, controlled delivery of antimicrobial agents, and promotion of wound healing. Our overarching hypothesis is that immunomodulation, combination of chemical, biological, and physical approaches, and micro-/nanofabrica- tion techniques will prevent ssis, eliminate biofilms, and promote wound healing. To accomplish this, we will pursue three projects: i) to test the hypothesis that immunomodulation would effectively prevent SSI and pro- mote wound healing; II) to test the hypothesis that engineered exosomes derived from immune cells and stem cells could express LL-37 for prevention of SSI and promotion of wound healing; and III) to test the hypothesis that combining chemical, biological, and physical approaches and micro-/nanofabrication technologies can erad- icate wound biofilms and promote wound healing. Building on work from our prior grants, we expect successful completion of the projects in this proposal will lay a strong foundation for developing the next generation of novel therapeutic anti-infective wound sutures and dressings that could greatly reduce rates of ssis, eliminate biofilms, speed healing, and minimize development of antibiotic resistance.