ABSTRACT
Corneal transplantation is the most effective clinical treatment for corneal defects, but it requires precise size of donor corneas, surgical sutures, and overcoming other technical challenges. Postoperative patients may suffer graft rejection and complications caused by sutures. Ophthalmic glues that can long-term integrate with the corneal tissue and effectively repair the focal corneal damage are highly desirable. Herein, a hybrid hydrogel consisting of porcine decellularized corneal stroma matrix (pDCSM) and methacrylated hyaluronic acid (HAMA) was developed through a non-competitive dual-crosslinking process. It can be directly filled into corneal defects with various shapes. More importantly, through formation of interpenetrating network and stable amide bonds between the hydrogel and adjacent tissue, the hydrogel manifested excellent adhesion properties to achieve suture-free repair. Meanwhile, the hybrid hydrogel not only preserved bioactive components from pDCSM, but also exhibited cornea-matching transparency, low swelling ratio, slow degradation, and enhanced mechanical properties, which was capable of withstanding superhigh intraocular pressure. The combinatorial hydrogel greatly improved the poor cell adhesion performance of HAMA, supported the viability, proliferation of corneal cells, and preservation of keratocyte phenotype. In a rabbit corneal stromal defect model, the experimental eyes treated with the hybrid hydrogel remained transparent and adhered intimately to the stroma bed with long-term retention, accelerated corneal re-epithelialization and wound healing. Giving the advantages of high bioactivity, low-cost, and good practicality, the dual-crosslinked hybrid hydrogel served effectively for long-term suture-free treatment and tissue regeneration after corneal defect.
ABSTRACT
Conventional administration of eye drops often requires high dosages and/or repetitive treatments to achieve therapeutic efficacy. This is inefficient and may result in side effects or even toxicity. Although many delivery systems of ophthalmic drugs have been reported, most of them work in a fixed format in which both the type and dose of the loaded drugs cannot be changed upon demand. To overcome this limitation, a hybrid double network hydrogel system composed of methacryloyl gelatin, pluronic F127 diacrylate, and ß-cyclodextrin-modified oxidized dextran was developed. The hydrogels presented good mechanical strength and biocompatibility. In vitro assessments demonstrated that the hydrogels loaded with commonly used ophthalmic drugs could sustain the drug release for more than 21 days. This hydrogel system exhibited features of mechanoresponsive drug loading, and the capacity of drug loading could be significantly enhanced by macroscopically mechanical compression. Further in vivo evaluation of the drug delivery capacity showed that a dexamethasone-loaded hydrogel as a fornix insert effectively suppressed upregulation of proangiogenic factors and suture-induced corneal neovascularization in rats. This novel hydrogel system represents a promising drug delivery platform, which could potentially improve the treatments of ocular surface and other diseases.
