In this study, an injectable, photocurable gelatin system, consisting of acrylated gelatin and thiolated gelatin, with tunable mechanical, biodegradation, and biological properties was used as a potential cell-supportive scaffold for the repair of focal corneal wounds. The mechanical property of hydrogels can be readily modified (postcure shear modulus of between 0.3 and 22 kPa) by varying the ratio of acrylate to thiol groups, photointensity, and solid content, and the biodegradation times also varied with the change of solid content. More importantly, the generated hydrogels exhibited excellent cell viability in both cell seeding and cell encapsulation experiments. Furthermore, the hydrogels were found to be biocompatible with rabbit cornea and aided the regeneration of a new tissue under a focal corneal wound (exhibiting epithelial wound coverage in <3d), and ultraviolet irradiation did not have any obvious harmful effect on the cornea and posterior eye segment tissues. Along with their injectability and tunable mechanical properties, the photocurable thiol-acrylate hydrogels showed promise as corneal substitutes or substrates to construct a new corneal tissue.
Because of their ease of handling and excellent biocompatibility, injectable macroporous hydrogels have received a considerable interest in the fields of tissue engineering and drug delivery systems because of their unique application in minimally invasive surgical procedures. In this study, in situ forming, injectable, macroporous, self-healing gelatin (GE)/oxidized alginate (OSA)/adipic acid dihydrazide (ADH) hydrogels were prepared using a highspeed shearing treatment and were stabilized by Schiff base reaction and acylhydrazone bonds. Their injectability, self-healing ability, rheology, microstructure, equilibrium water content, and in vitro biodegradation were investigated. We found that the injectable GE/OSA/ADH precursors remained in a liquid form and flowed easily for several minutes at room temperature, but however, gelled rapidly at body temperature. The gelation time could be regulated by varying the ratio of GE, OSA, and ADH. The obtained hydrogels had an interconnected macroporous structure and self-healing ability. The porosity of hydrogels was in the range of approximately 60−83%, and pore size varied from approximately 125−380 μm. The porous structure of hydrogel was visualized by field-emission scanning electron microscope, micro-computed tomography, and laser confocal microscope. Human epidermal growth factor was loaded by in situ mixing in GE/OSA/ADH hydrogels and was released with good bioactivity as evaluated by ELISA. Moreover, L929 cells proliferated on GE/OSA/ADH hydrogels, as verified by Cell Counting Kit-8 and LIVE/DEAD assays. Furthermore, encapsulation of NIH 3T3 cells within GE/OSA/ADH hydrogels demonstrated that the hydrogel can support cell survival, proliferation, and migration. In vivo studies showed that the hydrogels had a good injectability, in situ gelation, and tissue biocompatibility. Therefore, GE/OSA/ADH hydrogel represented a novel and safe injectable macroporous self-healing hydrogel for tissue engineering scaffold and drug delivery vehicle purposes.
To enhance the epithelization of poly(2-hydroxyethyl methacrylate) hydrogels and provide a biocompatible alternative for keratoplasty, this paper presents a novel double network scaffold and its preparation methods, in which a cell-affinitive hydrogel was made by poly(2-hydroxyethyl methacrylate) and modified gelatin. Methacrylic anhydride modified gelatin was interpenetrated into the as-prepared poly-2-hydroxyethyl methacrylate to form a porous double network to facilitate cell behavior on the hydrogels. Physico-chemical measurements such as X-ray photoelectron spectroscopy, transparency, swelling ratio, scanning electron microscopy, thermal gravimetric analysis as well as dynamic mechanical analysis have been performed in order to correlate the material composition with the corresponding properties. The in vitro cell assays of the porous double networks revealed that cells remained viable and, depending on the composition, were able proliferate, as was demonstrated by the deposition of gelatin. All of these results demonstrated that these porous double networks possess more advantages compared with poly(2-hydroxyethyl methacrylate) alone and improved epithelization due to methacrylated gelatin. The obtained double network scaffold could act as an attractive material for corneal repair application.
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