# Corneal Reconstruction through an In Situ-Forming Collagen Gel

> **NIH VA I21** · VETERANS ADMIN PALO ALTO HEALTH CARE SYS · 2021 · —

## Abstract

As the dome-shaped, transparent outermost part of the eye, the cornea provides the majority of the
focusing power for the visual pathway. When damaged due to severe injury or disease, its normally
smooth contour and optical clarity are often lost, resulting in reduced vision and, in many cases,
blindness. Restoration of normal corneal structure and function in Service Members and Veterans with
vision-compromising corneal injuries and disease is a priority. In spite of the various types of cadaveric
corneal transplants that are available, there remains a major clinical need for new modalities to rapidly
reconstruct and regenerate corneal tissue after severe injury or disease.
We propose to develop a novel, sutureless, corneal tissue substitute that stabilizes deep ulcers, defects,
and thinned areas of the cornea. The material is applied to a corneal wound as a viscous liquid, forming
a crosslinked, transparent gel within minutes that recreates the smooth, air-cornea interface necessary
for clear vision, while also promoting rapid epithelialization. This technology leverages a novel collagen
crosslinking modality known as copper-free click chemistry that is bio-orthogonal: it does not react with
proteins, cells, or biologic systems of any kind. As such, it can be safely applied to the surface of a
wounded cornea without producing toxic side products, and without the need for potentially harmful
external catalysts or triggers.
We hypothesize that while a bio-orthogonally, in situ-crosslinked, collagen gel alone may promote rapid
epithelialization and wound stabilization, its long-term biointegration and transparency will be enhanced
by the presence of encapsulated corneal stromal stem cells that can re-model the applied matrix without
causing fibrotic changes. We will test this hypothesis by evaluating the in vitro and in vivo performance
of the collagen gel with and without encapsulated corneal stromal stem cells. Corneal stromal stem cells
are known to secrete factors critical to preserving the transparency of the cornea if they are able to
quiescently differentiate into keratocytes rather than myofibroblasts. In preliminary work, we have shown
that bio-orthogonally crosslinked collagen gels are able to encapsulate corneal stromal stem cells and
facilitate keratocytic morphology, and also support the formation of a multi-layered epithelium ex vivo.
Motivated by this data, our first aim is to characterize and control the biological response of corneal tissue
to in situ-crosslinked collagen gels in vitro. Our second aim is to evaluate the biointegration and functional
performance of in situ- crosslinked collagen gels as a corneal stromal substitute in vivo. This research
will increase understanding of a novel class of sutureless, in situ-forming tissue scaffolds to reconstruct
corneal tissue. The results from these studies will build the foundational data for a VA Merit Award and
future clinical translation of this technology for the benefit of Serv...

## Key facts

- **NIH application ID:** 10249065
- **Project number:** 5I21RX003179-03
- **Recipient organization:** VETERANS ADMIN PALO ALTO HEALTH CARE SYS
- **Principal Investigator:** David Myung
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-07-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10249065

## Citation

> US National Institutes of Health, RePORTER application 10249065, Corneal Reconstruction through an In Situ-Forming Collagen Gel (5I21RX003179-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10249065. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*