Alginate-Based Composites for Corneal Regeneration: The Optimization of a Biomaterial to Overcome Its Limits

Abstract

For many years, corneal transplantation has been the first-choice treatment for irreversible damage affecting the anterior part of the eye. However, the low number of cornea donors and cases of graft rejection highlighted the need to replace donor corneas with new biomaterials. Tissue engineering plays a fundamental role in achieving this goal through challenging research into a construct that must reflect all the properties of the cornea that are essential to ensure correct vision. In this review, the anatomy and physiology of the cornea are described to point out the main roles of the corneal layers to be compensated and all the requirements expected from the material to be manufactured. Then, a deep investigation of alginate as a suitable alternative to donor tissue was conducted. Thanks to its adaptability, transparency and low immunogenicity, alginate has emerged as a promising candidate for the realization of bioengineered materials for corneal regeneration. Chemical modifications and the blending of alginate with other functional compounds allow the control of its mechanical, degradation and cell-proliferation features, enabling it to go beyond its limits, improving its functionality in the field of corneal tissue engineering and regenerative medicine.

Alginate-Based Biomaterials in Tissue Engineering and Regenerative Medicine

“…Alginates with biocompatibility, non-toxicity, and biodegradability can be deployed for corneal TE-RM, but more elaborative studies are still required to overcome the challenges pertaining to the optimal manufacturing and processing conditions for obtaining alginate-based composites with specific properties [ 88 ]. A micro-patterned bioadhesive film with a double-layered structure was developed using silk nanofibrils and gelatin methacrylate-alginate, leading to the sustained release of ascorbic acid for corneal regeneration as well as stimulation of the attachment, alignment, and proliferation of corneal stroma cells ( Figure 5 ) [ 89 ].…”

“…The hydrogel could significantly improve epithelial reconstruction, leading to rapid and efficient corneal wound healing [ 90 ]. It appears that several challenges still exist to specifically control the mechanical and degradation properties of these alginate-based composites for corneal TE-RM purposes [ 88 ]. The blend of alginate hydrogels with the protein derived from the ECM (e.g., gelatin and collagen) could provide an improvement in cell adherence, proliferation, and viability in alginate networks.…”

“…The blend of alginate hydrogels with the protein derived from the ECM (e.g., gelatin and collagen) could provide an improvement in cell adherence, proliferation, and viability in alginate networks. At the post-crosslinking stages, the utilization of suitable chelating agents along with the employment of oxidized alginate form could help improve the biodegradability, drug kinetic release, and functionality of the final alginate-based TE composites [ 88 ].…”

Biodegradable Polymer-Based Drug-Delivery Systems for Ocular Diseases

“…The burgeoning domain of ocular tissue engineering and regenerative medicine also acknowledges the value of alginate. Its similarity to the natural extracellular matrix composition allows it to function as an optimal scaffold for cell proliferation and differentiation, with studies exploring its use in corneal and retinal tissue reconstruction [ 73 , 74 , 75 ].…”

3D cell culture model: From ground experiment to microgravity study

“…From an architectural perspective, the fibrous network of hydrogels with relatively large (on the order of millimeter size) holes makes it easy for cell growth, spreading, and metabolic chemicals to move between cells (Kikuchi et al, 2017). Because of these properties, hydrogels have been widely used in tissue engineering (Hou et al, 2022;Tarsitano et al, 2022).…”