Engineering Tunable Biomimetic Adhesive Hydrogel to Deliver and Enhance MSC Function for Corneal Regeneration

NIH RePORTER · EY · R01 · $527,987 · view on reporter.nih.gov ↗

Abstract

Project Summary Corneal diseases pose a significant public health challenge in the United States, often leading to vision impairment and decreased quality of life. Mesenchymal stem cell (MSC) delivery to the cornea after a severe injury has shown promise by accelerating repair and significantly suppressing inflammation. However, a major bottleneck in developing MSC therapy for corneal repair is the lack of effective delivery methods. Moreover, optimizing the dosage and timing of MSC therapy is crucial for achieving therapeutic outcomes while minimizing side effects. MSCs must also survive and integrate into corneal tissue to exert their therapeutic effects. To date, MSCs have been delivered via surface injection, fibrin gel, or as a sheet on an amniotic membrane. However, these methods are limited by poor MSC survival and/or rapid matrix degradation. To address these issues, we propose the development of adhesive hydrogels that can effectively encapsulate and release MSCs in a sustained manner while having similar biomechanics as the corneal tissue. Our platform composed of a single hybrid polymeric structure with tunable variables to generate two distinct mechanical properties and degradation rates: 1) a soft/controlled degradable adhesive hydrogel to function as a bandage containing MSCs that release secreted factors for promoting corneal epithelial regeneration and 2) a strong/highly adhesive hydrogel that can adhere to corneal stromal defects and simultaneously serves as a stromal replacement while providing a platform for the delivery of MSCs to promote repair of stromal injuries/ulcerations. Our proposed biomaterial is a photocurable adhesive composite hydrogel based on chemically modified gelatin and hyaluronic acid (HA), encapsulated with MSCs. First, gelatin will be dual-functionalized with methacrylic anhydride (MA) and phenylboronic acid (PBA) to control mechanical properties and promote tissue adhesion. The incorporation of methacrylate HA derivatives in

Key facts

NIH application ID
11276657
Project number
1R01EY038446-01
Recipient
UNIVERSITY OF CALIFORNIA LOS ANGELES
Principal Investigator
Nasim Annabi; ALI R DJALILIAN; Reza Dana
Activity code
R01
Funding institute
EY
Fiscal year
2026
Award amount
$527,987
Award type
1
Project period
2026-05-01T00:00:00 → 2030-04-30T00:00:00