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.

Highlights

  • 10 g of silkworm cocoons from bombyx mori (Kyebong Farm, Cheongyang, Korea) were boiled in 0.02 M of sodium carbonate (Na2 CO3, Showa Chemical, Tokyo, Japan) that was dissolved in distilled water (DW) at 100 ◦ C for 30 min to remove the sericin

  • The final concentration of the silk fibroin (SF) solution was 8% (w/v) and the SF solution was stored at 4 ◦ C until further use

  • These results show that the 0.5% gellan gum (GG)/3.5% SF/chondroitin sulfate (CS) hydrogel can effectively maintain chondrocytes in substrate-generated phenotypes

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Summary

Introduction

One of the major challenges faced by developed societies today is the transition to a much older population. Osteoarthritis (OA) is a challenge and priority in healthcare systems around the world [1]. Damaged cartilage is difficult to self-recover due to its avascular, aneural, and nonlymphatic properties, and it leads to OA [2]. Several surgical methods such as microfractures, bone grafts, and prosthetic joint replacements are employed to treat cartilage defects [3,4].

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