Biomaterials for Corneal Regeneration

Abstract

Corneal blindness is a significant reason for visual impairment globally. Researchers have been investigating several methods for corneal regeneration in order to cure these patients. Biomaterials are favored due to their biocompatibility and capacity to promote cell adhesion. A variety of natural and synthetic biomaterials, along with decellularized cornea, have been employed in corneal wound healing. Commonly utilized natural biomaterials encompass proteins such as collagen, gelatin, and silk fibroin (SF), as well as polysaccharides including alginate, chitosan (CS), hyaluronic acid (HA), and cellulose. Synthetic biomaterials primarily consist of polyvinyl alcohol (PVA), poly(ε-caprolactone) (PCL), and poly (lactic-co-glycolic acid) (PLGA). Bio-based materials and their composites are primarily utilized as hydrogels, films, scaffolds, patches, nanocapsules, and other formats for the treatment of blinding ocular conditions, including corneal wounds, corneal ulcers, corneal endothelium, and stromal defects. This review attempts to summarize in vitro, preclinical, and clinical trial studies relevant to corneal regeneration using biomaterials within the last five years, and expect that these experiences and outcomes will inspire and provide practical strategies for the future development of biomaterials for corneal regeneration. Furthermore, potential improvements and difficulties for these biomaterials are discussed.

Keywords: biomaterials; corneal regeneration; natural materials; synthetic polymers; tissue engineering.

Figure 1

Biomaterials for corneal regeneration.

Figure 2

Development and evaluation of collagen‐based corneal substitutes. A) Schematic showing the electrochemically triggered kinetic assembly of collagen I. Adapted with permission.^{[ 24 ]} Copyright 2022, American Chemical Society. B) Six months after surgery, pachymetry maps depicting corneal thickness with thickness color‐coded. Adapted with permission.^{[ 25 ]} Copyright 2022, The Authors. C) Recombinant human collagen hydrogel featuring microstructures arranged in a hierarchical fashion. Adapted with permission.^{[ 26 ]} Copyright 2024, Elsevier B.V.

Figure 3

Development and evaluation of dECM‐based corneal substitutes. A) The fabrication process of LC‐COMatrix hydrogel.^{[ 54 ]} B) Rabbit corneal macroperforation healed in vivo using LC‐COMatrix hydrogel.^{[ 54 ]} C) In vitro repairs of corneal penetrations and perforations were used to evaluate the attachment strength of the LC‐COMatrix hydrogel. Burst pressure measurements were taken on a 2.75 mm full‐thickness cut injury. Adapted with permission.^{[ 54 ]} Copyright 2022, Wiley‐VCH GmbH.

Figure 4

Development and evaluation of gelatin‐based corneal substitutes. A) Chemical reaction schematic for the formation of GelCORE and the photocrosslinking of the prepolymer solution. Adapted with permission.^{[ 77 ]} Copyright 2019, The Authors. B) SEM captured at different magnifications of the grid scaffold demonstrates fiber spacing varying between 50 and 500 µm.^{[ 78 ]} C) Following 7 days of culture, LSSCs in SF medium on 2D TCPs, 3D GelMA, and the 100G construct were stained for cytoskeleton and ALDH3A1 expression. Adapted with permission.^{[ 78 ]} Copyright 2022, The Authors. D) Formation, application, and graphical representation of a light‐curable adhesive corneal cross‐linking hydrogel patch for the cornea. Adapted with permission.^{[ 79 ]} Copyright 2023, The Authors.

Figure 5

Development of gelatin‐based and SF‐based corneal substitutes. A) Schematic diagram of the GelMA/OHA hydrogel formation. Adapted with permission.^{[ 81 ]} Copyright 2022, Elsevier B.V. B) Proposed model of interaction between tropoe‐lastin and silk with its photographic image and Atomic Force Microscopy image. Adapted with permission.^{[ 83 ]} Copyright 2020, Elsevier B.V.

Figure 6

Schematic illustration of IonBAH. Adapted with permission.^{[ 99 ]} Copyright 2022, Wiley‐VCH GmbH.

Figure 7

Development and evaluation of polysaccharide‐based corneal substitutes. A) The interplay of corneal stromal stem cells and exosomes during ECM remodeling following anterior lamellar damage. Adapted with permission.^{[ 105 ]} Copyright 2021, Elsevier Ltd. B) Schematic illustrations of the pDCSM‐G/HAMA hydrogel. Adapted with permission.^{[ 57 ]} Copyright 2022, The Authors. C) Hyaluronate‐collagen hydrogel crosslinked via SPAAC. Adapted with permission.^{[ 110 ]} Copyright 2020, Elsevier Ltd.