# 3D bioprinting of regenerative, corneal cell-laden inks to treat corneal blindness

> **NIH NIH F31** · STANFORD UNIVERSITY · 2023 · $40,507

## Abstract

Project Summary
The demand for human donor tissue for treatment of corneal blindness far outpaces the supply, necessitating
an innovative bioengineered approach for corneal regeneration. However, current laboratory-made constructs
are insufficient due to lack of long-term transparency and underwhelming regenerative capacity. Recent studies
suggest that cell therapies using transplanted corneal mesenchymal stromal cells (MSCs) help prevent corneal
scar formation and restore corneal transparency. To propel this strategy toward clinical translation, both an
effective cell delivery system and a precise understanding of their regenerative effects will be required. 3D
bioprinting—in which cells and matrix components are precisely patterned—is a promising technique for creating
customizable corneal constructs for implantation. We have previously demonstrated a versatile, cell-friendly 3D
bioprinting platform for corneal MSCs. In my proposed research, I will apply 3D bioprinting for bioorthogonally-
crosslinked collagen hydrogels with encapsulated human corneal MSCs to fabricate highly regenerative corneal
stroma-like constructs. This system will allow for control over the corneal MSC microenvironment to optimize
and leverage their regenerative potential. I specifically aim to overcome two common challenges in
bioengineered corneal tissue that both result in loss of transparency: (1) tissue contraction over time due to cell-
imposed forces, and (2) lack of cell and matrix organization that mimics the hierarchical structure of the native
corneal stroma. I will test the hypotheses that (Aim 1) crosslinking collagen hydrogels with a covalent
bioorthogonal chemistry increases stability against contraction from corneal MSCs without hindering their ability
to secrete pro-regenerative factors and (Aim 2) aligning the collagen fibril microstructure through 3D bioprinting
guides the organized deposition of nascent matrix to facilitate sustained transparency. These constructs will be
evaluated in vivo (Aim 3) in a rabbit keratectomy model to assess restoration of corneal thickness, stromal
integrity, and optical transparency; integration of the hydrogel into the host; re-epithelialization; surface
inflammation and scarring; and phenotype of the transplanted corneal MSCs. Together, these results will be
critical for understanding the effect of the surrounding 3D matrix on the regenerative capacity of corneal MSCs.
My training will be supported by Sarah Heilshorn, Ph.D. (Materials Science & Engineering), an expert on
biomaterials for regenerative medicine, and David Myung, M.D., Ph.D. (Ophthalmology), an attending physician
who specializes in corneal surgery and diseases of the eye. In addition to expanding my scientific technical skills,
my training plan includes development of mentorship, scientific writing, and presentation skills; training in
research ethics; and enhancement of collaboration skills through a series of on-campus courses, workshops and
seminars as...

## Key facts

- **NIH application ID:** 10606474
- **Project number:** 1F31EY034785-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Lucia Brunel
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $40,507
- **Award type:** 1
- **Project period:** 2023-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10606474

## Citation

> US National Institutes of Health, RePORTER application 10606474, 3D bioprinting of regenerative, corneal cell-laden inks to treat corneal blindness (1F31EY034785-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10606474. Licensed CC0.

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