Further Investigations on Natural and Synthetic Bis-(1,2,3,4-tetrahydroisoquinoline) Derivatives Interacting with the Apamin-Sensitive Site of Small-Conductance Calcium-Activated Potassium Channels.

The cornea, located at the anterior portion of the eye, serves as a transparent and protective tissue that refracts incoming light onto the retina, enabling vision []. Structurally, it consists of three primary layers: the epithelium, stroma, and endothelium. Among these, the stroma constitutes nearly 85% of the total corneal thickness and is mainly composed of orthogonally arranged collagen (Col) fibrils, proteoglycans, and keratocytes []. The highly ordered lamellar architecture of these stromal components is crucial for maintaining both corneal transparency and mechanical stability []. Damage caused by trauma, infection, or degenerative diseases can disrupt this organization, resulting in stromal opacification and vision loss []. Corneal transplantation remains the clinical gold standard for visual restoration; however, its broad implementation is restricted by the global shortage of donor tissue, high costs, and potential immune rejection []. These limitations have motivated the development of alternative regenerative strategies, particularly tissue-engineered scaffolds designed to recapitulate the native stromal structure and function []. Among natural polymers, sodium alginate (SA) has attracted attention in corneal stromal engineering (CSE) due to its biocompatibility, hydrophilicity, and structural similarity to glycosaminoglycans, which support favorable cell–matrix interactions []. However, its intrinsic brittleness, rapid degradation, and limited optical clarity restrict its use as a standalone material []. To address these limitations, SA is often combined with other natural or synthetic polymers to improve mechanical and physicochemical properties. For instance, Tonsomboon et al. [,] demonstrated that embedding electrospun gelatin (Gel) nanofibers into SA–Gel hydrogels enhanced mechanical strength by nearly an order of magnitude while preserving transparency, indicating their potential as scaffolds for corneal transplantation when donor tissue is unavailable. Furthermore, Datta et al. [] showed that SA can be formulated into crosslinked nanoparticles with tunable stability, high drug loading, and enhanced mucoadhesion, demonstrating the polymer’s versatility for ocular applications and highlighting its potential for future bioactive or drug-delivering corneal scaffolds. Polyvinyl alcohol (PVA) is a promising candidate for CSE due to its optical transparency, flexibility, and tunable biodegradability []. PVA-based materials exhibit high mechanical strength, water retention, and oxygen permeability []. The incorporation of PVA into Col- or chitosan (CS)-based scaffolds enhances their tensile strength and light transmittance, thereby improving their suitability for corneal applications [,]. For example, Seyed et al. [] showed that PVA/CS nanofibrous scaffolds support corneal epithelial cell adhesion, proliferation, and phenotype maintenance while providing mechanical stability and transparency. Similarly, Ulag et al. [] demonstrated that 3D-printed PVA/CS corneal stroma constructs maintain optical clarity, mechanical robustness, and cell viability, highlighting the potential of PVA blends for fabricating patient-specific corneal scaffolds suitable for CSE. Recent studies have further demonstrated the potential of electrospun PVA-based and composite scaffolds for corneal tissue engineering. For example, Wu et al. [] developed an aligned PVA/Col nanofibrous scaffold capable of mimicking the native stromal architecture and promoting cellular organization. Jung et al. [] fabricated multilayered keratin/PVA electrospun scaffolds with enhanced physicochemical properties for corneal implantation. Likewise, Bakhshandeh et al. [] proposed a two-part artificial cornea consisting of a PVA hydrogel integrated with a polycaprolactone (PCL) nanofibrous ring, while Mirzaeei et al. [] developed single- and multilayered PVA/CS-based electrospun matrices for ocular drug delivery applications. These studies collectively demonstrate the versatility of PVA-based systems for ophthalmic applications while highlighting the continued need for scaffold designs that integrate structural reinforcement, optical transparency, and biomimetic architecture for CSE.