A comparative analysis of different cell-based approaches for promoting cartilage regeneration using a salidroside-loaded injectable hydrogel

Abstract Objective . Cartilage defects associated with temporomandibular joint osteoarthritis (TMJOA) demonstrate limited repair capacity and are influenced by a complex biomechanical environment, leading to suboptimal clinical repair outcomes. This study aims to develop an injectable hydrogel system incorporating salidroside (SAL) and to address two primary objectives. First, to optimize the hydrogel concentration to achieve effective SAL loading and controlled release. Second, to compare the cartilage regeneration potential of hydrogels loaded with chondrocytes versus those loaded with cultured cartilage tissue within an anti-inflammatory micro-environment. Methods . The material properties and anti-inflammatory effects of SAL were systematically evaluated in GelMA hydrogels at concentrations of 8%, 10%, and 12% to determine the optimal formulation. Subsequently, chondrocytes (CC) and cultured cartilage tissue (CT) were each incorporated into the optimized SAL-Gel to fabricate CC/SAL-Gel and CT/SAL-Gel composites. In vitro biocompatibility of both composites was initially assessed using Phalloidin staining and Live/Dead assays. Thereafter, the cartilage regeneration capacity of the two groups was compared through histological analyses, including HE, SO, and COL-2 staining, as well as evaluation of cartilage formation marker expression. Results . Material characterization indicated that the 10% GelMA hydrogel exhibited an optimal balance among mechanical strength, degradation rate, and sustained release of SAL. The incorporation of SAL effectively conferred anti-inflammatory properties. In vitro experiments demonstrated that the CT/SAL-Gel group significantly surpassed the CC/SAL-Gel group in preserving the cartilage phenotype and promoting extracellular matrix synthesis. Conclusion . This study successfully developed an injectable hydrogel system incorporating SAL. The results demonstrate that employing pre-formed cultured CT as a regenerative construct, in conjunction with the anti-inflammatory effects of SAL, more effectively facilitates the formation of functional cartilage-like tissue. These findings offer novel theoretical insights and practical strategies for advancing TMJ cartilage regeneration by leveraging the synergistic interaction between cultured tissue and an anti-inflammatory microenvironment.