Preparation and characterization of an injectable dexamethasone-cyclodextrin complexes-loaded gellan gum hydrogel for cartilage tissue engineering.

In this study, 6-(6-aminohexyl) amino-6-deoxy-ß-cyclodextrin-gellan gum complex hydrogel (HCD-GG) was developed to enhance the affinity of anti-inflammatory drug dexamethasone (Dx), improve chondrogenesis, and decrease the inflammatory response. The modified chemical structure was confirmed by NMR and FTIR. Mechanical and physicochemical properties were characterized by performing viscosity study, compression test, injection force test, swelling kinetic, weight loss, and morphological study. The release profile of the drug-loaded hydrogels was analyzed to confirm the affinity of the hydrophobic drugs and the matrix and characterize cumulative release. In vitro test was carried out with MTT assay, live/dead staining, glycosaminoglycan (GAGs) content, double-stranded DNA (dsDNA) content, morphological analysis, histology, and gene expression. In vivo experiment was conducted by implanting the samples under a subcutaneous area of SPD rat and cartilage defected rabbit model. The results displayed successfully synthesized HCD-GG. The gelation temperature of the modified hydrogels was decreased while the mechanical property was improved when the drug was loaded in the modified hydrogel. Swelling and degradation kinetics resulted in a higher level compared to the pristine GG but was a sufficient level to support drugs and cells. The affinity and release rate of the drug was higher in the HCD-GG group which shows an improved drug delivery system of the GG-based material. The microenvironment provided a suitable environment for cells to grow. Also, chondrogenesis was affected by the existence of Dx and microenvironment, resulting in higher expression levels of cartilage-related genes while the expression of the inflammation mediators decreased when the Dx was loaded. In vivo study showed an improved anti-inflammatory response in the drug-loaded hydrogel. Furthermore, the cartilage defected rabbit model showed an enhanced regenerative effect when the Dx@HCD-GG was implanted. These results suggest that HCD-GG and Dx@HCD-GG have the potential for cartilage regeneration along with multiple applications in tissue engineering and regenerative medicine.

Application of double network of gellan gum and pullulan for bone marrow stem cells differentiation towards chondrogenesis by controlling viscous substrates.

Hydrogels have a large amount of water that provides a cartilage-like environment and is used in tissue engineering with biocompatibility and adequate degradation rates. In order to differentiate stem cells, it is necessary to adjust the characteristics of the matrix such as stiffness, stress-relaxing time, and microenvironment. Double network (DN) hydrogels provide differences in cellular biological behavior and have interpenetrating networks that combine the advantages of the components. In this study, by varying the viscous substrate of pullulan (PL), the DN hydrogels of gellan gum (GG) and PL were prepared to determine the cartilage differentiation of bone marrow stem cell (BMSC). The characteristics of GG/PL hydrogel were investigated by examining the swelling ratio, weight loss, sol fraction, compressive modulus, and gelation temperature. The viability, proliferation, and toxicity of BMSCs encapsulated in hydrogels were evaluated. Cartilage phenotype and cartilage differentiation were confirmed by morphology, GAG content, and cartilage-specific gene expression. Overall results demonstrate that GG/PL hydrogels can form cartilage differentiation of BMSCs and can be applied for tissue engineering purposes.

Advanced gellan gum-based glycol chitosan hydrogel for cartilage tissue engineering biomaterial.

Gellan gum (GG), a nature-derived polysaccharide, is one of the materials widely used in cartilage tissue engineering (TE). Glycol chitosan (GC), a derivative of chitosan, is a water-soluble natural polymer that has excellent biocompatibility and biodegradability as well as cell adhesion. Herein, GG was physically blended with GC to enhance the mechanical properties and microenvironment of the GG to apply in cartilage TE. The study was conducted with a hydrogel model which is similar to the extracellular matrix (ECM) of cartilage tissue. The physicochemical studies were carried out with morphological study, swelling ratio, weight loss, and sol fraction. The mechanical characterization was conducted with compression test and rheological study to confirm availability in cartilage TE material. Furthermore, in vitro studies such as morphology investigation, viability assay, GAG content, qRT-PCR, and histological study were performed to verify biocompatibility and chondrogenesis of the material. The mechanical and biological properties improved with a proper amount of GC. Overall results verify the potential of the material and can be further used for the cartilage TE.

Characterization of Gelatin/Gellan Gum/Glycol Chitosan Ternary Hydrogel for Retinal Pigment Epithelial Tissue Reconstruction Materials.

The cellular transplantation approach to treat damaged or diseased retina is limited because of poor survival, distribution, and integration of cells after implantation to the sub-retinal space. To overcome this, it is important to develop a cell delivery system. In this study, a ternary hydrogel of gelatin (Ge)/gellan gum (GG)/glycol chitosan (CS) is suggested as a cell carrier for retinal tissue engineering (TE). Physicochemical properties such as porosity, swelling, sol fraction, and weight loss were measured. The mechanical study was performed with compressive strength and viscosity to confirm applicability in retinal TE. An in vitro experiment was carried out by encapsulating ARPE-19 in the designed hydrogel to measure viability and expression of retinal pigment epithelium-specific proteins and genes. The results showed that the ternary hydrogel system improves the mechanical properties and stability of the composite. Cell growth, survival, adhesion, and migration were enhanced as the CS was incorporated into the matrix. In particular, real-time polymerase chain reaction analysis showed a markedly improved specific gene expression rate in the Ge/GG/CS. Therefore, it is expected that the ternary system suggested in this study can be used as a promising material for retinal TE.

Evaluation of double network hydrogel of poloxamer-heparin/gellan gum for bone marrow stem cells delivery carrier.

In this study, a double network hydrogel of a natural polysaccharide gellan gum (GG) hydrogel and a synthetic hydrogel poloxamer-heparin (PoH) hydrogel (PoH/GG DNH) is introduced to complement disadvantages of each hydrogel and improve the microenvironment for cell delivery. The microstructure, surface morphology, gelation temperature, swelling and weight loss, sol fraction, mechanical property and thermal stability was examined. The potential of the composite hydrogel for cell vehicle was demonstrated by encapsulation of bone marrow stem cells isolated from rabbits (rBMSCs) within the PoH/GG DNH in vitro. The results showed that the DNH system supported cell survival and retained rBMSCs morphology and phenotype. Moreover, cell distribution, adherence, and ECM production were supported by PoH/GG DNH in vivo. Overall results provide a potential opportunity to apply the composite hydrogels in tissue engineering purpose.