# Regenerative Immunotherapy using light triggered in vivo activation of adhesive peptides

> **NIH NIH R56** · GEORGIA INSTITUTE OF TECHNOLOGY · 2020 · $429,912

## Abstract

Oronasal fistulas (ONF) following cleft palate repair remain a challenging problem that is frequently encountered clinically.
Preclinical evidence from our lab and multiple literature reports show that immune response, including monocyte
recruitment, is dysregulated in ONF, leading to a non-healing environment with scarring and a large fistula. This is a major
problem in the pediatric population which causes trouble talking and eating and requires repeat surgeries in these children
who are then still left with permanent defects. Prior research shows that non-classical monocytes are biased progenitors of
pro-angiogenic, anti-fibrotic macrophages within excisional skin and oral cavity wounds, and that they function within the
injury niche to enhance microvascular network expansion. This proposal seeks to develop new degradable poly(ethylene
glycol)-maleimide (PEG) hydrogels that are functionalized with photoactivatable caged RGD peptide. Preliminary data
shows that regulating the timing of immune cell adhesion in cutaneous tissues enhances regeneration. These findings suggest
that light triggering of stimulus-responsive hydrogel biomaterials is a potent new technology for initiating pro-regenerative
immune signaling. Because of the widespread potential application of light-initiated biomaterial responses in the oral cavity
(e.g. light-cured resin), this proposal will investigate whether local, time-regulated presentation of RGD in an oral cavity
repair model can prevent complications during oral cavity wound healing, similar to those observed following cleft palate
repair. The overarching hypothesis of these studies is that temporal control of light-triggered RGD presentation during oral
cavity wound healing will increase the adhesion of non-classical monocytes and enhance their pro-regenerative
contributions associated with vascularization, tissue remodeling and regeneration. This hypothesis will be addressed in the
following specific aims: Aim 1: To investigate the effects of spatial patterning and gradient presentation of light-triggered
RGD peptides in vivo on the recruitment of pro-regenerative monocyte / macrophage subsets. This aim will employ a dorsal
skinfold window chamber model for repetitive, non-invasive intravital microscopy analysis of monocyte recruitment
kinetics in situ after light-triggering. Aim 2: To investigate how time-regulated presentation of RGD from PEG hydrogels
influences pro-regenerative monocyte / macrophage subset recruitment and vascularization in a murine cleft palate repair
model. This aim will investigate immune infiltration and repair mechanisms in palatal wounds and will determine how the
time-regulated presentation of adhesive ligands from PEG hydrogels influences wound repair. This aim will also include
novel enhancement-of-function experiments using FTY720 delivery to increase pro-regenerative Ly6clo monocyte
accumulation. These experiments will determine whether light-triggering the exposure of RGD combined...

## Key facts

- **NIH application ID:** 10252435
- **Project number:** 1R56DE029703-01
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Edward A. Botchwey
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $429,912
- **Award type:** 1
- **Project period:** 2020-09-10 → 2022-09-11

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10252435

## Citation

> US National Institutes of Health, RePORTER application 10252435, Regenerative Immunotherapy using light triggered in vivo activation of adhesive peptides (1R56DE029703-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10252435. Licensed CC0.

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