Efficacy of photo-crosslinked gelatin hydrogel scaffolds loaded with tauroursodeoxycholic acid on knee cartilage defect repair in a rabbit model

doi:10.3969/j.issn.1674-8115.2025.07.004

Abstract

Abstract:

Objective ·To investigate the reparative effects of photo-crosslinked gelatin methylacrylated (GelMA) hydrogel scaffolds loaded with tauroursodeoxycholic acid (TUDCA) on cartilage defects in rabbit knee joints. Methods ·Photo-crosslinked GelMA hydrogel scaffolds loaded with TUDCA were prepared by the ultraviolet light irradiation method. The physicochemical properties of GelMA hydrogel scaffolds were characterized, and the cumulative release rate of TUDCA was determined. A rabbit knee cartilage defect model was established, and 18 rabbits were randomly assigned into three groups, with six rabbits in each group: the control group (no treatment was applied to the cartilage defect), the GelMA group (the cartilage defect was filled with GelMA hydrogel scaffold), and the GelMA+TUDCA group (the cartilage defect was filled with the GelMA hydrogel scaffold loaded with TUDCA). At 12 weeks postoperatively, the concentrations of two inflammatory factors in synovial fluid, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), were detected by enzyme-linked immunosorbent assay (ELISA). After euthanasia, knee cartilage samples were harvested for gross observation, safranin O-fast green staining, and toluidine blue staining. The repair of the cartilage defects was evaluated according to the International Cartilage Repair Society (ICRS) and Modified O′Driscoll Score (MODS) systems. Immunohistochemical staining was performed to detect type Ⅱ collagen (COL-Ⅱ) protein in the cartilage tissue, and Western blotting was used to assess the protein levels of aggrecan (ACAN) and COL-Ⅱ. Results ·GelMA hydrogel scaffolds exhibited a more compact microstructure after ultraviolet light irradiation, along with an suitable mass swelling ratio and compressive modulus. The TUDCA-loaded photo-crosslinked GelMA hydrogel scaffolds demonstrated effective and sustained TUDCA release, achieving a cumulative release rate of 90.2%±2.5% within 28 d. ELISA results showed that compared to the control and GelMA groups, the concentrations of TNF-α and IL-1β in the synovial fluid of the GelMA+TUDCA group were significantly reduced (P<0.001). In the GelMA+TUDCA group, the cartilage defects were nearly fully repaired, with a smooth surface and good integration with the surrounding tissue. The number of newly formed chondrocytes increased, displaying orderly alignment, and the neocartilage exhibited excellent formation. Both ICRS and MODS scores were significantly higher in the GelMA+TUDCA group than those in the control and GelMA groups (P<0.001). Additionally, the expression levels of ACAN and COL-Ⅱ proteins were significantly elevated in the GelMA+TUDCA group compared to the control and GelMA groups (P<0.001). Conclusion ·Photo-crosslinked GelMA hydrogel scaffolds loaded with TUDCA can effectively promote the repair of cartilage defects in rabbit knee joints.

Key words: cartilage defect, osteoarthritis, tauroursodeoxycholic acid, gelatin methylacrylated, chondrocyte, tissue engineering

CLC Number:

R782

WEI Xiang, WEI Lingfei, XU Chunfeng, GAO Yujie, NIE Ping, YU Dedong. Efficacy of photo-crosslinked gelatin hydrogel scaffolds loaded with tauroursodeoxycholic acid on knee cartilage defect repair in a rabbit model[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(7): 829-837.

Figures/Tables 7

Fig 1 Synthesis and physicochemical characterization of GelMA hydrogel scaffolds

Fig 2 Fabrication of GelMA/TUDCA hydrogel scaffolds and the release kinetics of TUCDA from the scaffolds

Fig 3 Concentrations of IL-1β and TNF-α in knee synovial fluid detected by ELISA

Fig 4 Morphological observation and ICRS scores of repaired knee articular cartilage defects in each group

Fig 5 Histological observation and MODS scores of repaired knee articular cartilage defects

Fig 6 Immunohistochemical staining of COL-Ⅱ in repaired knee articular cartilage defects

Fig 7 ACAN and COL-Ⅱ protein levels in repaired knee articular cartilage defects detected by Western blotting

TrendMD

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