# Nanofiber-based Delivery of Combined Immune-modulating Compounds to Minimize Infection and Enhance Wound Healing

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2021 · $340,836

## Abstract

ABSRTACT
Despite major efforts to keep operating rooms sterile, surgical site infections (SSIs) remain a serious and stub-
born problem, killing up to 8,200 patients a year in the U.S. Our long-term goal is to develop novel therapies that
effectively minimize risk of SSIs and promote wound healing. During the previous funding cycles of this award,
we have demonstrated that i) successful encapsulation and sustained release of vitamin D and other immuno-
modulating compounds induced higher cathelicidin antimicrobial peptide (CAMP) gene and protein (hCAP18/LL-
37) levels in immune cells and keratinocytes in cell culture, a human CAMP transgenic mouse wound model and
human skin explants; ii) topical vitamin D increased killing of Staphylococcus aureus in a skin wound-infection
model using our human CAMP transgenic mouse; and iii) exosomes secreted from immune cells treated with
vitamin D contained higher levels of hCAP18/LL-37. Furthermore, we developed a novel gas-foaming expansion
technique to fabricate improved 3D nanofiber scaffolds eluting vitamin D that promoted immune cell infiltration,
induced hCAP18/LL-37, decreased inflammation, and promoted neovascularization and collagen deposition in
human immune system-engrafted mice. Building on these findings, and our preliminary data, the goal of our
proposal focuses on the development of nanofiber-based dressings for enhancing innate immunity. Our over-
arching hypothesis is that co-encapsulating immunomodulating compounds with exosomes secreted from
treated immune cells in 3D nanofiber scaffolds will synergistically enhance protection against SSIs and promote
wound healing better than either component alone. To accomplish this, there are three specific aims: 1) Demon-
strate efficient encapsulation and elution of immunomodulating compounds from our improved 3D nanofiber
scaffolds; 2) Determine the antimicrobial and wound-healing efficacy of exosomes derived from primed or human
CAMP transfected immune cells; and 3) Demonstrate the efficacy of immunomodulating compounds and exo-
somes - co-incorporated 3D nanofiber scaffolds to promote healing and prevent infection in our humanized trans-
genic mouse model and ex vivo human skin explants. Building on work from our prior grant, we expect successful
completion of the aims in this renewal will lay a strong foundation for developing the next generation of novel
therapeutic anti-infective wound dressings that could greatly speed healing, reduce rates of SSIs and minimize
development of antibiotic resistance. We also expect these dressings could serve as effective treatments for
traumatic and combat-related injuries.

## Key facts

- **NIH application ID:** 10299094
- **Project number:** 2R01GM123081-05
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Jingwei Xie
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $340,836
- **Award type:** 2
- **Project period:** 2017-05-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10299094

## Citation

> US National Institutes of Health, RePORTER application 10299094, Nanofiber-based Delivery of Combined Immune-modulating Compounds to Minimize Infection and Enhance Wound Healing (2R01GM123081-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10299094. Licensed CC0.

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