Collagen-sodium alginate-silk fibroin 3D-printed scaffold loaded with polydatin promotes cartilage regeneration by improving lipid metabolism and cell apoptosis

Abstract

Cartilage defects negatively impact the quality of life of over 500 million people worldwide. 3D-printed scaffolds loaded with polydatin (PD) have shown significant potential in cartilage defect repair. This study aims to investigate their reparative effects and analyze the associated metabolic changes using lipidomics techniques, providing new strategies for treating cartilage defects. Biocompatible 3D-printed scaffolds containing PD were prepared and 30 New Zealand rabbits were divided into three groups (10 rabbits per group) that underwent either sham surgery (Normal group) or surgical creation of a cartilage defect without scaffold filling (Model group) or with the developed scaffold filling (Scaffold group). After three months of intervention, the repair of cartilage defects was evaluated through macroscopic observation, micro-CT, hematoxylin and eosin (H&E) staining, and Safranin O/fast green (SFO/FG) staining. The expression of vascular endothelial growth factor A vascular endothelial growth factor A (VEGFA), Col2a1, and biglycan was detected by immunofluorescence while lipid metabolic profiling analysis was conducted on newly formed cartilage tissue to comprehensively evaluate the scaffold’s mechanism of action. Macroscopic observation, micro-CT, H&E staining, and SFO/FG staining indicated that the repair of cartilage defects in the Scaffold group was significantly better than in the Model group, closely resembling the Normal group. Lipidomics revealed that the Scaffold group modulated 36 metabolites, with a recovery rate of 69.23%, including ceramides (Cers), glycerophospholipids (GPs), and sphingomyelins (SMs). Immunofluorescence analysis showed increased expression of cartilage cell markers Sox9, Col2a1, biglycan, and VEGFA, along with a reduction in cell apoptosis (all p <0.05) after scaffold implantation. These findings collectively suggest that the PD-loaded 3D-printed scaffold promotes cartilage repair by restoring lipid metabolites in cartilage tissue, inhibiting chondrocyte apoptosis, enhancing vascular-related protein expression, and accelerating cartilage collagen matrix remodeling.

Keywords

3D printing / Cartilage regeneration / Lipid metabolism / Cell apoptosis / Polydatin

Funding

This research was supported by multiple funds from the following: the National Natural Science Foundation of China (No. 81904053); Zhejiang Provincial Natural Science Foundation of China (No. LTGY24H290006); Zhejiang Province Medical and Health Science and Technology Project (No. 2025KY191); Special Research Project of the Affiliated Hospital of Zhejiang Chinese Medical University (No. 2021FSYYZY43); Hangzhou Science and Technology Planning Project (No. 20220919Y084); Zhejiang Province Traditional Chinese Medicine Science and Technology Project (No. 2023ZR046); and Hangzhou Bio-Medicine and Health Industry Development Support Science and Technology Project (Nos. 2023WJC243 and 2023WJC249).

Conflict of interest

All the authors declare that they have no conflicts of interest.

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