# Characterization of corneal stromal stem cells encapsulated within bioorthogonally crosslinked collagen gels for delivery to the ocular surface

> **NIH NIH F31** · STANFORD UNIVERSITY · 2022 · $39,777

## Abstract

When the cornea is damaged due to severe trauma or disease, its normally smooth contour and optical
clarity are often compromised, resulting in loss of vision. The standard of care in these cases involves corneal
transplantation; however, donor tissue remains limited in most parts of the world and unavailable to many who
need it. Although there have been promising results in the creation of biosynthetic tissue graft materials,
recapitulating the long-term transparency, biomechanics, and regenerative capacity of a human donor cornea
remains a formidable challenge. Previous research has demonstrated that stem cell therapy could be an
alternative option to donor tissue, and it was shown that transplanted corneal stromal stem cells (CSSCs) can
prevent corneal scar formation and restore corneal transparency. However, cell viability following simple
injection remains low due to mechanical damage during the injection procedure. In addition, CSSC phenotype
post-transplantation and the mechanism behind their regenerative potential remain unknown. Therefore, new
methods for delivering CSSCs and understanding how they respond to extracellular environment to facilitate
corneal transparency are needed.
 In this proposed research, I will develop a bioothogonally crosslinked collagen gel with tunable
mechanical properties that I hypothesize can successfully deliver CSSCs to the wounded cornea, stabilize the
wound, and promote rapid re-epithelization while maintaining corneal transparency. We have previously
demonstrated that bioorthogonal crosslinking can improve the mechanical stability of collagen while avoiding
the potential off-target and cytotoxic effects of typical crosslinking chemistries. Here, I will determine how the
culturing CSSCs in the gel matrix affects the gel’s mechanical properties and prolonged transparency over time
as a function of bioorthogonal crosslinking density. I will also characterize how the crosslinking density affects
the phenotypic transition of CSSCs to keratocytes and determine how the 3D culture conditions affect the
CSSCs transcriptome. Then I will evaluate the paracrine role of the CSSCs in re-epithelization of the damaged
cornea, including differences in the expression of growth factors and how the engineered gel is integrated into
native tissue. This will advance our basic understanding of how CSSCs contribute to corneal transparency by
remodeling their extracellular matrix and how their surrounding microenvironment influences their
differentiation and regenerative potential. Ultimately, this work could provide a platform technology to enable
wound healing inside and outside the eye.

## Key facts

- **NIH application ID:** 10357733
- **Project number:** 5F31EY030731-03
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Sarah Hull
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $39,777
- **Award type:** 5
- **Project period:** 2020-03-30 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10357733

## Citation

> US National Institutes of Health, RePORTER application 10357733, Characterization of corneal stromal stem cells encapsulated within bioorthogonally crosslinked collagen gels for delivery to the ocular surface (5F31EY030731-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10357733. Licensed CC0.

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