FXa-Responsive Hydrogels to Craft Corneal Endothelial Lamellae

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Cell-instructive polymer hydrogels are crucial for tissue engineering but lack controlled responsiveness.
• Developing stimuli-responsive hydrogels that selectively degrade is a significant challenge.

Purpose of the Study:

• To introduce a modular hydrogel system with tunable degradation for controlled tissue release.
• To demonstrate the hydrogel's utility in engineering and transplanting human corneal tissue.

Main Methods:

• Fabrication of a hydrogel using four-arm poly(ethylene glycol)-peptide and glycosaminoglycan-maleimide conjugates.
• Incorporation of a peptide sequence cleavable by coagulation factor FXa for triggered hydrogel disintegration.
• Ex vivo culture, detachment, and in vitro transplantation of human corneal endothelial lamellae using the hydrogel system.

Main Results:

• The hydrogel remained stable in cell culture without FXa, supporting tissue growth.
• Introduction of FXa led to rapid hydrogel degradation and gentle release of engineered tissues.
• Successful ex vivo development and detachment of human corneal endothelial lamellae suitable for Descemet Membrane Endothelial Keratoplasty (DMEK).

Conclusions:

• The FXa-cleavable hydrogel system offers a versatile platform for scaffold-free tissue engineering.
• This technology enables controlled release of functional tissues, advancing organoid regenerative therapies.
• The system holds potential for next-generation regenerative medicine applications, including corneal transplantation.