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Vitreous, an essential dioptric medium for the human eyes, must be filled with artificial materials once damaged. Carboxymethyl chitosan (CMCTS) is one of the most important water-soluble chitosan derivatives with improved biocompatibility and biodegradability. In this study, oxidized hyaluronic acid (OHA) was prepared as crosslinking reagent. CMCTS and OHA were used to develop a biocompatible, self-repairing and in-situ injectable hydrogel for vitreous substitutes. Results showed the hydrogel with controllable swelling properties, high transparency, acceptable cytocompatibility on mouse fibroblast L929 and histocompatibility in vivo. Furthermore, hydrogel was injected in-situ into the vitreous cavity after vitrectomy on New Zealand Rabbits, no significant and persistent adverse effects were observed during the 90-day follow-up period. In addition, the hydrogel maintained intraocular pressure of the operated eyes and the inherent position of the retina. Collectively, this injectable, biodegradable, nontoxic hydrogel possessed enormous potential to become a vitreous substitute material.

Although various biopolymers and synthetic compounds have been proposed and tested as the vitreous substitutes, no ideal material has been identified yet. In the present study, we developed an in situ-formed hydrogel by crosslinking hydroxypropyl chitosan with alginate dialdehyde. Physical properties of the hydrogel were studied and the cytotoxicity was evaluated using L929 fibroblasts, rabbit corneal endothelial cells and retinal pigment epithelial cells. In a preliminary in vivo study, the hydrogel was employed as vitreous substitute after vitrectomy surgery on rabbits and multiple parameters indicating biosafety and biocompatibility were measured and analyzed postoperatively. Our results showed that the refractive index, transmittance, pH value and density of the hydrogel were similar to those of human vitreous. Cytotoxicity tests demonstrated the hydrogel to be nontoxic to all of the three cell lines selected. Using the rabbit model, we showed that the hydrogel could form in situ and postoperative analysis of slit-lamp observation, intraocular pressure, corneal endothelium examination, B-scan ultrasound and fundus photography showed no significant adverse reactions in the operated eyes during the 90-day follow-up. However, electroretinogram and histopathological examinations indicated minor vision decline and decrease of the densities of cones and rods in the operated rabbit eyes. Collectively, our study suggested that the in situ-formed hydrogel could potentially be used as a vitreous substitute, with its long-term safety and efficacy to be further assessed. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1997-2006, 2018.

Hydroxyethyl chitosan (HECTS) is a critical derivative of chitosan that has been widely used as biomedical materials due to great water-solubility and excellent biocompatibility. Here, photosensitive hydroxyethyl chitosan was synthesized by introducing azide group on NH2 of HECTS (HECTS-AZ), afterwards FTIR and 1H NMR spectra were detected to confirm the formation of HECTS-AZ. The solution of HECTS-AZ can achieve a sol–gel transition through UV irradiation for 30 s. The evaluation of biocompability and biodegradability in vivo was conducted in rats, visual and pathological examinations exhibited the HECTS-AZ has excellent biocompability and degradation time of the hydrogel is more than 14 weeks. Furthermore, HECTS-AZ hydrogel as an ocular drug delivery system loading heparin was prepared to implant under sclera of rabbit after glaucoma filtration surgery (GFS). The experimental results demonstrated the heparin loaded hydrogel can effectively maintain filtration bleb and lowing intraocular pressure (IOP) after GFS for prolonged time. Besides, obvious inflammatory reactions and side effects have not been observed in ocular during the experimental period. In conclusion, the HECTS-AZ hydrogel is a potential drug delivery device for the treatment of glaucoma and other ocular diseases.

A novel chitosan-based membrane that was made of hydroxypropyl chitosan, gelatin and chondroitin sulfate was used as a carrier of corneal endothelial cells. The characteristics of the blend membrane, such as transparency, equilibrium water content, permeability, mechanical properties, protein absorption ability, hydrophilicity and surface morphology, were determined. To study the effects of the membrane on cell attachment and growth, rabbit corneal endothelial cells were cultured on this artificial membrane. The biodegradability and biocompatibility of the blend membrane were in vivo evaluated by its implantation into the muscle of the rats. Glucose permeation results demonstrated that the blend membrane had higher glucose permeability than natural human cornea. Scanning electron microscopy (SEM) analysis of the membranes demonstrated that no fibrils were observed. As a result, the optical transparency of the membrane was as good as the natural human cornea. The average value of tensile strength of the membrane was 13.71 MPa for dry membrane and 1.48 MPa for wet membrane. The value of elongation at break of the wet was 45.64%. The cultured rabbit corneal endothelial cells formed a monolayer on the blend membrane which demonstrated that the membrane was suitable for corneal endothelial cells to attach and grow. In addition, the membranes in vivo showed a good bioabsorption property. The mild symptoms of inflammation at sites of treatment could be resolved as the implant was absorbed by the host. The results of this study demonstrated that the hydroxypropyl chitosan-chondroitin sulfate-gelatin blend membrane can potentially be used as a carrier for corneal endothelial cell transplantation.

A novel chitosan-based membrane that made of hydroxyethyl chitosan, gelatin and chondroitin sulfate was used as a carrier of corneal endothelial cells. The characteristics of the blend membrane including transparency, equilibrium water content, ion and glucose permeability were determined. The results showed that the optical transparency of the membrane was as good as the natural human cornea. The water content of this scaffold was 81.32% which was remarkably close to the native cornea. The membrane had a good ion permeability and its glucose permeability was even higher than natural human cornea. The cultured rabbit corneal endothelial cells formed a monolayer on the membrane. The results demonstrated that the membrane was suitable for corneal endothelial cells to attach and grow on it. In addition, the membranes in vivo could be degraded steadily with less inflammation and showed a good histocompatibility. These results demonstrated that the hydroxyethyl chitosan-chondroitin sulfate-gelatin blend membrane can potentially be used as a carrier for corneal endothelial cell transplantation.

Biodegradable hydrogels are important biomaterials for tissue engineering and drug delivery. For the purpose of corneal regenerative medicine, we describe an in situ formed hydrogel based on a water-soluble derivative of chitosan, hydroxypropyl chitosan (HPCTS), and sodium alginate dialdehyde (SAD). Periodate oxidized alginate rapidly cross-links HPCTS due to Schiff's base formation between the available aldehyde and amino groups. Hydrogel cytotoxicity, degradability and histocompatibility in vivo were examined. The potential of the composite hydrogel for corneal endothelium reconstruction was demonstrated by encapsulating corneal endothelial cells (CECs) to grow on Descemet's membranes. The results demonstrate that the composite hydrogel was both non-toxic and biodegradable and that CECs transplanted by the composite hydrogel could survive and retain normal morphology. These results provide an opportunity for corneal endothelium reconstruction based on tissue engineering by the in situ formed composite hydrogel.