Regenerative Medicine in the Cornea

The potential role of bioengineering and three-dimensional printing in curing global corneal blindness

“…Due to this complication, most keratoprostheses employ the “core and skirt” design ( Figure 1 ) which involves a transparent core that is surrounded by porous material that enables host cellular association and the anchoring of the prosthesis through fibroblast in-growth. 36 Poly(methyl methacrylate) (PMMA) was the first synthetic polymer to be used in artificial cornea construction, and the introduction of the “core and skirt” model slightly improved the rate of successful prosthokeratoplasties. However, insufficient host tissue integration into the prosthetic skirts remains one of the significant barriers to the creation of a scalable keratoprosthetic design successful in the majority of cases.…”

“… 37 – 41 It is notable that keratoprostheses can fail due to retroprosthetic membrane formation and calcification in addition to the more general keratoplasty complications of infection, glaucoma, and retinal detachment. 36 Synthetic keratoprostheses have historically carried increased risk of microbial infection or prosthesis protrusion due to their inability to support intact epithelium establishment. 42 Extrusion of the keratoprosthesis is largely due to necrosis around the edge of the prosthesis and consequent dislodging.…”

Corneal Tissue Engineering: Recent Advances and Future Perspectives

“…Despite the critical role of innervation in corneal functions, few attempts have been made to induce peripheral nerve proliferation within corneal tissue-engineered constructs. In vitro studies have shown that decoration of substrate with laminin-derived peptides promoted epithelial stratification and Griffith et al, 59 and Liu et al 77 Color images available online at www.liebertpub.com/teb 282 GHEZZI ET AL.…”

“…58 The combination of synthetic polymers together with natural-derived materials provides enhanced biological responses and more amenable optical properties. 59 As an example, hydrogels films prepared from chitosan blended with poly(ethylene glycol) and poly (l,d lactic acid) nanofibers in a composite with type I collagen hydrogel displayed improved mechanical, optical, and biological performances compared with synthetic fibers alone. 56,60 Among the natural polymers, hydrogels from reconstituted type I collagen offer the advantage of encapsulating living cells and, 61 particularly in the context of the human cornea, are widely used due to type I collagen dominant content in the corneal stroma.…”

“…However, due to insufficient mechanical properties and the susceptibility to cell-mediated remodeling and degradation, chemical cross-linkers are commonly used with type I collagen hydrogels for corneal stromal replacements or regeneration. 59,62,63 Alternatively, organized arrays of electrospun type I collagen nanofibers have been developed to provide spatial guidance to corneal fibroblasts, although reducing construct transparency. 64 In an effort to combine mechanical, biological, and optical properties, corneal stromal substrates from silk films have been developed by optimizing topography, surface chemistry, porosity, and degradation profiles, demonstrating a capability to support corneal stromal cell differentiation in 2D and 3D film architectures (Fig.…”