SMART peptides-loaded HYdrogel deriVed from acellular cornea: an Innovative Strategy for corneal regeneratION - (Acronym: SmarthyVision)

The human eye is an extraordinary organ formed by the coordinated development of multiple tissues, with contributions of neuroectodermal, ectodermal, and mesodermal origin. The impairment of any of these ocular tissues can lead to blindness. To date, diseases affecting the cornea represent the most common causes of blindness in the world. The human cornea, together with the surrounding sclera, constitutes the protective outer barrier of the eye. It exerts two essential functions, protecting from external physical trauma and providing about 70% refractive power of the eye. To perform these functions, the corneal tissue is both mechanically strong and transparent. The direct contact of the cornea with the external environment makes it frequently exposed to various types of injuries. To date, the surgical replacement of lesioned cornea with healthy donor tissue is the most frequently used therapeutic approach. However, the high cost, the high graft failure rate, the legal issues, and the lack of donors, require new options for treating corneal lesions (Golchet et al., 2000; Gain et al., 2016). The actual challenge is to discover new therapeutic compounds promoting the regeneration of the native cornea in patients. The aim of this project is to realize and validate an innovative regenerative-based therapy for the treatment of corneal damage. Specifically, the goal is to investigate the therapeutic potential of an innovative injectable adhesive hydrogel based on the acellular porcine cornea which functions as a scaffold to promote corneal tissue ingrowth, and serves as a delivery depot for pituitary adenylate cyclase-activating polypeptide (PACAP) and/or activity-dependent neuroprotective protein (ADNP)-derived peptide (NAP), which will be used for prompt and long-term repair of corneal alterations. The project will be achieved over the two years by completing the following work packages (WPs): • WP_1: Synthesis and chemical-physical characterization of the peptides-loaded hydrogel obtained from the decellularization of the porcine cornea. • WP_2: In vitro cytocompatibility of peptides-loaded hydrogel on human corneal epithelial, human corneal endothelial cells, and human corneal keratocytes. • WP_3: In vivo assessment of peptides-loaded adhesive hydrogel in a rat model of corneal injury. The innovation of the research proposed is the optimization of a smart strategy able to (1) provide the appropriate enriched substrate to promote corneal tissue regeneration, (2) restore normal tissue function in vivo, and (3) guide and enhance the corneal native regenerative ability. The therapeutic efficacy and feasibility of the project will be extensively investigated both in vitro and in vivo. The successful conclusion of the project could yield an essential stepping-stone toward the development of a promising therapeutic intervention for the treatment of corneal wounds in the clinical setting.