ECM‐Like Adhesive Hydrogel for the Regeneration of Large Corneal Stromal Defects

Abstract

The repair of large‐diameter corneal stroma defects is a major clinical problem. Although some studies have attempted to use hydrogels to repair corneal damage, most of these hydrogels can only be used for focal stromal defects that are ≤3.5 mm in diameter due to poor hydrogel adhesion. Here, a photocurable adhesive hydrogel that mimics the extracellular matrix (ECM) with regard to composition for repairing 6 mm‐diameter corneal stromal defects in rabbits is investigated. This ECM‐like adhesive can be rapidly cured after light exposure, with high light transmittance and good mechanical properties. More importantly, this hydrogel maintains the viability and adhesion of cornea‐derived cells and promotes their migration in vitro in 2D and 3D culture environments. Proteomics analysis confirms that the hydrogel promotes cell proliferation and ECM synthesis. Furthermore, in rabbit corneal stromal defect repair experiments, it is proven by histological and proteomic analysis that this hydrogel can effectively promote corneal stroma repair, reduce scar formation, and increase corneal stromal–neural regeneration at the six months follow‐up. This work demonstrates the great application of ECM‐like adhesive hydrogels for the regeneration of large‐diameter corneal defects.

ECM-based bioadhesive hydrogel for sutureless repair of deep anterior corneal defects

“…14,15 Regarding recent studies, it is well stated that light-curable hydrogels provide a durable chemical bond to the host tissue compared to other gelation forms of hydrogels, which exhibit weak physical adhesion through poor hydrogen bonding. 8 A photocurable dCor sealant developed using a ruthenium/sodium persulfate photoinitiator exhibited a greater compressive modulus as well as higher bioadhesion strength than dCor hydrogels. 15 Another study used dCor in blend with methacrylated hyaluronic acid (HAMA) and a photoinitiator to form amide bonds between the hydrogel and adjacent corneal tissue, which revealed good sealing performance along with improved mechanical strength and stability.…”

“…7 However, these materials have some deficiencies in corneal regeneration, such as poor biocompatibility, weak adhesion to wet surfaces of host tissue, and inflexibility, which have encouraged the investigation of more appropriate strategies for developing corneal bioadhesive sealants. 8 A bioadhesive corneal patch or hydrogel must carry the desired functions for a corneal substitute such as transparency, epithelium and stroma regeneration, suturelessness, and toughness. 1 Hydrogels derived from the decellularized corneal extracellular matrix (dCor), as a natural biomaterial, have attracted great attention for corneal regeneration because of the preserved specific chemical signals of the native extracellular matrix (ECM), which can influence cellular processes such as differentiation toward tissue-specific cells.…”

Smart molecules in ophthalmology: Hydrogels as responsive systems for ophthalmic applications

“…[165] Modulation of the GelMA and HA ratios in an ECM-like hydrogel were shown to enhance cell viability through the modulation of corneal microenvironment. [166] More recently, Qian and colleagues have developed a highly transparent bioadhesive, with higher adhesion power, biocompatibility, and regenerative properties to meet the needs in ophthalmology. [167] In situ oxidative free-radical polymerization of GelMA with dopamine methacrylamide was shown to enhance corneal epithelial cell proliferation, while preventing proinflammatory microenvironment by decreasing ROS accumulation.…”

Organic–inorganic composite hydrogels: compositions, properties, and applications in regenerative medicine

“…As scaffolds, hydrogels can mimic the structure and function of the extracellular matrix (ECM) existing in natural tissues, providing friendly microenvironments for cell growth and differentiation, helping to achieve the final tissue regeneration by regulating cell behaviors with different designs. 8 As delivery carriers, hydrogels can transport drugs and peptides to target tissues and control their release profiles. 9 However, tissue regeneration is a complex dynamic process involving tissues with different mechanical properties and ECM components.…”