Development and Evaluation of Gellan Gum/Silk Fibroin/Chondroitin Sulfate Ternary Injectable Hydrogel for Cartilage Tissue Engineering

Abstract

Hydrogel is in the spotlight as a useful biomaterial in the field of drug delivery and tissue engineering due to its similar biological properties to a native extracellular matrix (ECM). Herein, we proposed a ternary hydrogel of gellan gum (GG), silk fibroin (SF), and chondroitin sulfate (CS) as a biomaterial for cartilage tissue engineering. The hydrogels were fabricated with a facile combination of the physical and chemical crosslinking method. The purpose of this study was to find the proper content of SF and GG for the ternary matrix and confirm the applicability of the hydrogel in vitro and in vivo. The chemical and mechanical properties were measured to confirm the suitability of the hydrogel for cartilage tissue engineering. The biocompatibility of the hydrogels was investigated by analyzing the cell morphology, adhesion, proliferation, migration, and growth of articular chondrocytes-laden hydrogels. The results showed that the higher proportion of GG enhanced the mechanical properties of the hydrogel but the groups with over 0.75% of GG exhibited gelling temperatures over 40 °C, which was a harsh condition for cell encapsulation. The 0.3% GG/3.7% SF/CS and 0.5% GG/3.5% SF/CS hydrogels were chosen for the in vitro study. The cells that were encapsulated in the hydrogels did not show any abnormalities and exhibited low cytotoxicity. The biochemical properties and gene expression of the encapsulated cells exhibited positive cell growth and expression of cartilage-specific ECM and genes in the 0.5% GG/3.5% SF/CS hydrogel. Overall, the study of the GG/SF/CS ternary hydrogel with an appropriate content showed that the combination of GG, SF, and CS can synergistically promote articular cartilage defect repair and has considerable potential for application as a biomaterial in cartilage tissue engineering.

Chitosan/Pluronic F127 Thermosensitive Hydrogel as an Injectable Dexamethasone Delivery Carrier

“…On the other hand, the morphology of the C28/I2 cells was analyzed after being seeded on the surface of the hydrogels for 72 h. Cell shape plays an important role in the phenotypic expression of chondrocytes. The rounded morphology indicates characteristics of the chondrogenic phenotype [ 57 , 58 ]. Figure 3 B shows the SEM micrographs of the cells seeded in the materials, (a) CS1-PF25 and (b) CS1-PF25-TPP.…”

Fabrication and Characterization of Chicken- and Bovine-Derived Chondroitin Sulfate/Sodium Alginate Hybrid Hydrogels

“…However, no distinct peak change were observed between the FTIR spectra of the SA, CCS/SA (1/3), CCS/SA (2/3), BCS/SA (1/3), and BCS/SA (2/3) hydrogels in this study. This demonstrated that the cross-linking reaction between CS and SA was a physical process, and no chemical cross-linking occurred between the polymers [ 30 ].…”

Advanced injectable hydrogels for cartilage tissue engineering

“…Naturally derived polymers are widely used in injectable hydrogels for repairing cartilage defects due to their excellent biodegradability, biocompatibility, and similar 3D microenvironment in vivo . However, rapid degradation, poor mechanical properties, and enhanced microenvironment for cell proliferation and differentiation are challenges in practical applications ( Jian et al, 2012 ; Lee et al, 2021 ). The combination of natural and synthetic polymers can play to their respective strengths and compensate for their weaknesses ( Peng et al, 2019 ; Li et al, 2021c ).…”