Functionalized hydrogel-based corneal bandage for treatment of corneal diseases

Abstract

The cornea serves as a barrier for eye against the external environment, while the optimal barrier hinges upon the completeness of the corneal structure. However, the cornea is constantly exposed to a range of threats from the outside environment, such as pathogen invasion and physical injury. Bacterial keratitis is commonly encountered that can rapidly deteriorate the cornea which can give rise to complications, including severe damage to the corneal epithelial layer. Excessive use of antibiotics for treatment of bacterial keratitis can result in the emergence of drug-resistance. Consequently, development of a treatment method to effectively eliminate bacteria without fostering drug-resistance becomes an urgent necessity. Furthermore, it is imperative to facilitate the recovery of the impaired corneal epithelial layer and other corneal tissues once the bacteria are eradicated to prevent subsequent corneal inflammation or scarring. Approaches have been explored for management of these corneal disease. Notably, hydrogels garnered growing interest due to their excellent transparency, exceptional biocompatibility, and ease of modification. This study primarily centers around the development of a treatment approach for bacterial keratitis and epithelial defect, utilizing a modified biocompatible hydrogel, poly-lysine (PεK) hydrogel. Near-infrared activated nanomaterials were encapsulated within PεK hydrogel to fabricate an antibacterial tear-responsive photo-activated hydrogel bandage (tgr-PAHB), with the aim of treating bacterial infections. The antibacterial efficacy and biocompatibility of tgr-PAHB were evaluated through in-vitro investigations. Tgr-PAHB exhibited exceptional antibacterial capabilities, achieving nearly 100% elimination of Pseudomonas aeruginosa, while maintaining approximately 90% viability of epithelial cells. Additionally, tgr-PAHB demonstrated promising ability to eliminate drug-resistant bacteria in ex-vivo models compared to antibiotics employed in clinical treatment. Following the successful development of the tgr-PAHB, our endeavors extended to the construction of a living corneal bandage (LCB) for healing of substantial corneal epithelial defects. A scaffold-free cell planar structure was prepared within an aqueous two-phase system and subsequently transferred onto a PεK hydrogel to form the LCB. In-vitro experiments substantiated that cells in LCB retain proliferation and migration capabilities. Furthermore, ex-vivo investigations demonstrate that the application of the LCB promptly filled the epithelial defect, covering over 50% of the affected area following transplantation. These findings supported that the LCB holds the promise as a viable approach for the treatment of extensive epithelial defects. Additionally, constructing of cell structures with diverse spatial shapes was also conducted within an all-aqueous system aiming at regenerating damaged corneal tissue. By introducing a controllable droplet phase, cell structures exhibiting monolayer and hollow configurations can be fabricated with the ability to vary in size accordingly. Explorations to the physical nature of the aqueous system and the assembly behavior of the cells were conducted to enhance the control of synthesis. These results showcase the potential for precise manipulation of cell structures, which can inspire avenues for the regeneration of injured corneal tissue. This study provides potential approaches with modified hydrogels for treatment of bacterial keratitis and epithelial defects, as well as methods for preparing various cell structures for corneal tissue regeneration. These innovative solutions may be developed and undergo commercialization in the future.