Fabrication and characterization of poly(ε-caprolactone)/gelatin nanofibrous scaffolds for retinal tissue engineering

Retinal cell regeneration using tissue engineered polymeric scaffolds

“…Future research should also investigate the use of scaffolds as dual-purpose platforms, to both regenerate cells and deliver drugs and biologics to target ocular tissues. PCL Synthetic Biocompatible; nontoxic; low cost; elastic, easy pore size and shape control; slow degradation rate (24 and 48 months); PCL nanofibrous scaffolds prepared by electrospinning; scaffold with high surface-to-volume ratio; high porosity (85%); high pore interconnectivity; sufficient tensile strength; promoted cell proliferation; scaffolds prepared by electrospinning with smaller pore size; PCL fiber orientation similar to native collagen; scaffolds prepared by electrospinning with average pore size 13.3±5.5 mm and thickness 114±16 mm maintaining high cell viability; similar fiber orientation to native collagen in ECM; pore size: 1.2 m; promote cell attachment and proliferation; nanofibrous scaffold of PCL and gelatin with lower cytotoxicity [48,61,68,109,110] PCL-treated plasma Synthetic Biocompatible; convenient; cost-effective; nanofibrous scaffolds prepared by electrospinning with porous structure, good cell adhesion and proliferation [110] PLGA Synthetic FDA approved;, biodegradable; biocompatible;, tailored degradation time; limited flexibility; degrade within weeks; scaffold prepared by electrospinning technique with pore size of 10.4±6.2 mm and thickness of 109±17 mm maintained high cell viability and preserved human corneal epithelial cell morphology; scaffold of PLLA and PLGA; high degree of porosity; uniform pore structure; controllable configurations and thickness; poor flexibility; caused inflammatory, fibrosis and foreign body responses; bulk degradation resulted in non-uniform release profile [66,93] PLDLA Synthetic Hydrophilic; similar mechanical properties to PLC with shorter degradation time; scaffolds with relatively high membrane porosity with surface coating to mimic collagen on BrM; enhance interaction with cells and tissues [111] PMMA Synthetic No foreign body response; limitations to supporting cell growth; toxic; nondegradable; scaffolds prepared by electrospinning with pore size diameter of 26.8±17.5 mm and thickness of 150±12 mm; lowest viscosity resulted in thickest fibers, largest interstitial spaces, thickest scaffolds, and best light transmission [65,66] Parylene-C Synthetic Biocompatible; nontoxic; good mechanical strength and biostability; semipermeable to macromolecules when thickness reduced to submicron range; mesh-supported submicron membrane; can withstand significant stretching force; epithelial-like morphology; tight intracellular junctions; correct polarization; well-developed microvilli; good cell adherence [112] A C C E P T E D M A N U S C R I P T…”

“…The simplest way to deliver cells to the retina is the direct injection of a cell suspension into the vitreous humor. This approach has resulted in disorganized or incorrectly localized grafts along with reflux of cells from the injection site [48]. Additionally, the injected cells might not survive or diffuse through the viscous vitreous humor to reach the target site.…”

“…Furthermore, they should not trigger any inflammatory, adverse, or immunological responses that might result in scaffold rejection by the body [18]. So far, a large variety of biomaterials has been used to prepare ophthalmic scaffolds, including: natural proteins, such as collagens [4,60] and gelatin [61,62]; natural polysaccharides, such as alginate [63,64] and chitosan [65]; and synthetic polymers, such as poly lactic-co-glycolic acid (PLGA) [66,67] and poly(ε-caprolactone) (PCL) [48,68]. Each of these polymers has its own advantages and disadvantages [18].…”

“…Indeed, hybrid scaffolds (synthetic and natural biomaterials) show enhanced properties when the synthetic components of the scaffold control the structural properties, whereas the natural components provide natural signals [78]. For example, PCL-gelatin scaffolds can act as a substrate for RPE cells in vitro, whereby the presence of gelatin improves the hydrophilicity and biodegradation rate of the scaffold, and PCL enhances the physical properties of the scaffold and reduced its cytotoxicity [48]. In another study, cationic chitosan-graft-PCL hybrid scaffolds were fabricated that improved the proliferation and differentiation of murine retinal progenitor cells compared with PCL scaffolds [79].…”

“…The fabrication of nanofibrous scaffold comprising silk fibroin and poly(Llactic-co-ε-caprolactone) has potential application for retinal progenitor cells [98]. Additionally, the fabrication of electrospun porous PCL/gelatin scaffolds for subretinal implantation has also been reported [48], as has the fabrication of ultrathin nanofibrous scaffolds based on collagen and PLGA. Interestingly, the fiber diameter and packing density were similar to native human BrM, enabling the seeded human RPE cells to grow and form a correctly oriented monolayer with a polygonal structure and abundant sheet-like microvilli on apical surfaces of cells [70].…”