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.

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.

Characterization and Potential of a Bilayered Hydrogel of Gellan Gum and Demineralized Bone Particles for Osteochondral Tissue Engineering.

Osteochondral (OC) tissue engineering (TE) is a promising strategy to regenerate acute or degenerative chondral and OC lesions. However, advancing a proper model for OC TE is still under way. Herein, a bilayer hydrogel (BH) based on gellan gum (GG) hydrogel and demineralized bone particles (DBPs) is suggested as a new model. The BH composite can be fabricated easily with a cell-friendly biomaterial and cross-linker. The BH composite was characterized by a morphological method and physicochemical aspect. The mechanical and rheological characters were further confirmed to verify its applicability in OC TE. The thermodynamic property of the composite was determined to analyze thermal stability and interaction among matrices. The bioactivity of the material was studied by treating simulated body fluid (SBF) solution for 28 days to examine the formation of crystalline structure in the BH construct. In vitro studies were carried out to study the viability and biochemical characters of the developed biomaterial. An in vivo study was performed to analyze the biocompatibility of the material and regeneration of the injured OC region implanted with BH composites. The data displayed stable physicochemical properties and mechanical characters when the DBPs were incorporated with a proper amount. The bioactivity of the DBP-loaded hydrogels displayed a high amount of apatite formation. The cytotoxicity of the fabricated material was low, which allows application in vitro and in vivo. The biochemical studies displayed a high level of alkaline phosphatase (ALP) activity and gene expression, which shows promising application of DBP-loaded GG in the bone layer of the BH model. The long-term in vivo study displayed excellent biocompatibility and great potential in the OC defected region. Overall, these results suggest the significance of combined and innovative approaches to improve the therapeutic strategies for OC regeneration, and the BH model suggested in this study can be a promising biomaterial model for OC 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.