Fiber reinforced GelMA hydrogel to induce the regeneration of corneal stroma

Abstract

Regeneration of corneal stroma has always been a challenge due to its sophisticated structure and keratocyte-fibroblast transformation. In this study, we fabricate grid poly (ε-caprolactone)-poly (ethylene glycol) microfibrous scaffold and infuse the scaffold with gelatin methacrylate (GelMA) hydrogel to obtain a 3 D fiber hydrogel construct; the fiber spacing is adjusted to fabricate optimal construct that simulates the stromal structure with properties most similar to the native cornea. The topological structure (3 D fiber hydrogel, 3 D GelMA hydrogel, and 2 D culture dish) and chemical factors (serum, ascorbic acid, insulin, and β-FGF) are examined to study their effects on the differentiation of limbal stromal stem cells to keratocytes or fibroblasts and the phenotype maintenance, in vitro and in vivo tissue regeneration. The results demonstrate that fiber hydrogel and serum-free media synergize to provide an optimal environment for the maintenance of keratocyte phenotype and the regeneration of damaged corneal stroma.

Application of bioactive hydrogels combined with dental pulp stem cells for the repair of large gap peripheral nerve injuries

“…However, due to the poor thermostability and low melting point, gelatin is required for chemical modifications to overcome the shortcomings and avoid thermo reversibility [ 25 , 27 ]. When gelatin is chemically modified by methacryloyl (MA) then crosslinked by photoinitiator at a fixed wavelength of light, a gelatin methacryloyl (GelMA) hydrogel is synthesized with excellent thermostability [ 25 , 28 , 29 ]. Meanwhile, GelMA hydrogel keeps up the most of functional amino acid motifs (e.g.…”

Prospects and Challenges of Translational Corneal Bioprinting

“…Regeneration of corneal stroma has always been an obstacle in tissue engineered approaches, due to its sophisticated microstructure, consisting of orthogonally aligned collagen nanofibrous lamellae [87]. The transparency and mechanical properties of the stroma are attributed to its unique tight packing and uniform diameter of collagen fibers.…”

“…The transparency and mechanical properties of the stroma are attributed to its unique tight packing and uniform diameter of collagen fibers. A recent study fabricated orthogonally aligned PCL-PEG sub-micro fibers, which were perfused by rat LSC-loaded 15% GelMA hydrogel, to form 3D fiber-reinforced constructs ( Figure 3 B) [ 87 ]. The combination of the PCL-PEG fibers with the 15% GelMA gel improved the strength of the constructs to address issues with the suture-ability.…”

“…Fluorescent staining shows cellular filopodial extensions up to 50 µm. Scale bars represent 10 mm (left) and 100 µm (right) [ 87 ]. ( C ) Extrusion bioprinting of human turbinate-derived mesenchymal stem cells cultured in CSK differentiation media and embedded in a cornea-derived decellularized ECM bioink.…”

Spatiotemporally Controlling the Release of Biological Effectors Enhances Their Effects on Cell Migration and Neurite Outgrowth

“…For example, uniaxially aligned fibers can be stacked orthogonally to obtain a grid-type of scaffold, upon which the cytoskeletons of cells will be extended along two perpendicular directions. [58] In addition, during the electrospray process, a mask can also be introduced between the needle and the collector to deposit PCM microparticles loaded with specific types of biological effectors onto certain regions of the scaffold, giving more flexibility in controlling the spatiotemporal distributions of various types of biological effectors. This technique should be extendible to other types of scaffolds such as hydrogels and 3D porous sponges, as long as the PCM microparticles loaded with biological effectors can be integrated into the scaffold and the NIR light can penetrate through and reach the microparticles.…”