Table 2.
Summary of current advances in natural hydrogel formulations for corneal tissue engineering.
| Natural Base Material (s) | Novelty | Research Model | Ref. | ||
|---|---|---|---|---|---|
| Material Characterization | Cells for In Vitro Evaluation | In Vivo or Ex Vivo Studies | |||
| Epithelium | |||||
| Silk fibroin | Production of transparent silk hydrogels with tunable mechanical properties using organic solvents and metal ions | –Mechanical properties –Morphology –Transparency |
–Human CEpCs –Human dermal fibroblasts |
-- | [47] |
| Collagen/gelatin/alginate | Three-dimensional printing human CEpCs laden constructs with tunable degradation based on varying inclusion of sodium citrate | –Degradation –Morphology –Transparency |
–Human CEpCs | -- | [51] |
| Collagen | Methacrylation of collagen for improved flexibility |
–Degradation –Mechanical properties –Spectroscopy |
–Human CEpCs –Murine CPCs |
-- | [52] |
| Gelatin | Injectable, photocurable gelatin system, consisting of acrylated gelatin and thiolated gelatin, with tunable mechanical, biodegradation, and biological properties |
–Degradation –Mechanical properties –Morphology –Spectroscopy –Transparency |
–L929 murine fibroblasts | –Focal corneal injury in NZW rabbits | [67] |
| Chitosan | Thermosensitive chitosan-gelatin hydrogels releasing stromal cell derived factor-1 alpha |
–Morphology | –Rat LESCs –Rat MSCs |
–Alkali burn-injury in SD rats | [30] |
| Stroma | |||||
| Silk fibroin | PVA/silk/nano-hydroxyapatite hydrogels with structurally enhancing genipin crosslinking | –Degradation –Mechanical properties –Morphology |
–Human CFs | -- | [48] |
| Collagen | Three-dimensional printed collagen-I based bio-ink with varied amounts of methacrylated collagen and sodium alginate | –Mechanical properties –Morphology –Transparency |
–Human CKs | -- | [53] |
| Collagen | Bio-orthogonally crosslinked hyaluronate-collagen hydrogel | –Degradation –Mechanical properties –Morphology –Transparency |
–Human CEpCs | –Anterior lamellar keratoplasty in NZW rabbits | [54] |
| Collagen | 3D printable collagen/agarose | –Mechanical properties –Transparency |
–Human CKs | -- | [55] |
| Gelatin | Gelatin/ascorbic acid cryogels | –Degradation –Mechanical properties –Morphology –Spectroscopy |
–Rabbit CKs | –Anterior lamellar keratoplasty in NZW rabbits | [68] |
| GelMA | Visible light cross-linkable | –Degradation –Mechanical properties |
–Human CFs | –Half thickness stromal defect in NZW rabbits | [69] |
| GelMA | Three-dimensional printed using stereolithography | –Morphology –Transparency |
–Human CSCs | -- | [70] |
| GelMA | GelMA hydrogel with PCL-PEG scaffold support | –Mechanical properties –Transparency |
–Rat LSSCs | –Intrastromal keratoplasty in SD Rats | [71] |
| GelMA | Hybrid Cellularized GelMA and decellularized bovine corneal ECM | –Degradation –Mechanical properties –Spectroscopy –Transparency |
–Bovine CKs | -- | [72] |
| GelMA | Three-dimensional printed with organized, encapsulated keratocytes |
–Degradation –Mechanical properties –Morphology –Spectroscopy –Transparency |
–Human CKs | -- | [73] |
| Bacterial Cellulose |
Composite Bacterial cellulose and PVA | –Morphology –Transparency |
–Human CSCs | –Intrastromal keratoplasty in NZW rabbits | [31] |
| Endothelium | |||||
| GelMA | Nanopatterning and hybrid crosslinking for improved monolayers |
–Degradation –Mechanical properties –Morphology –Spectroscopy |
–Human CEnCs | –Anterior keratoplasty in NZW rabbits | [74] |
| HA | Porous HA hydrogel as endothelial cell sheet delivery system |
–Degradation –Morphology |
–Rabbit CEnCs | –Endothelial scrape wound in NZW rabbits | [32] |
| Poly-ε-lysine | Porous hydrogel for expansion of corneal endothelial cells with improved expansion when ECM proteins were adsorbed to the surface |
–Mechanical properties –Transparency –Contact angle |
–Human CEnCs (HCEC-12) –Porcine CEnCs |
[21] | |
| Full Thickness | |||||
| Collagen | Bottom-up assemblies of decellularized porcine corneal sheets and human CSC laden collagen gel layers with human CEpCs seeded at top surface |
–Degradation –Transparency |
–Human CSCs –Human CEpCs |
–Ex vivo porcine anterior lamellar keratoplasty model | [57] |
| Collagen + Laminin | Laser assisted bioprinting with collagen and laminin-based inks |
–Degradation –Morphology |
–Human LESCs –Human ASCs |
-- | [58] |
| Collagen-like peptides | Collagen-like peptides/PEG/fibrinogen liquid hydrogel matrix that gels spontaneously at body temperature | –Mechanical properties –Transparency |
–Human CEpCs | –Epithelial perforation wound in NZW rabbits –Anterior lamellar keratoplasty in Gottingen mini pigs |
[59] |
| Collagen | Dual-layered collagen vitrigel with synthetic Bowman’s membrane and stromal layer. Contains ECM microparticles |
–Degradation –Mechanical properties –Morphology –Transparency |
–Rabbit CFs | –Anterior lamellar keratoplasty in NZW rabbits | [60] |
| Collagen | In situ forming collagen gels crosslinked with PEG-NHS have tunable transparency, degradation, and stiffness |
–Degradation –Mechanical properties –Transparency |
–Human CEpCs –Human LSSCs |
–Keratectomy in NZW rabbits | [61] |
| Decellularized Porcine cornea | Thermoresponsive in situ forming hydrogel | –Mechanical properties –Morphology –Transparency |
–Human CEpCs –Human MSCs |
-- | [33] |