Astragalus polysaccharide-containing 3D-printed scaffolds promote cartilage regeneration by correcting metabolic disorders and promoting cellular matrix remodeling

<i>Background</i>: Astragalus polysaccharide-containing 3D-printed scaffolds show great potential for cartilage defect repair. The aim of this study is to investigate their repairing role, combine them with metabolomics technology to deeply analyze the related metabolite changes, and provide a new strategy for the treatment of cartilage defects. <i>Methods</i>: Biocompatible astragalus polysaccharide-containing 3D-printed scaffolds were prepared. Thirty New Zealand rabbits were divided into normal, model and scaffold groups, with 10 rabbits in each group. The repair of cartilage defects by the scaffolds was evaluated by gross observation, micro-CT, HE and ABH staining after 12 weeks of intervention. The expression of VEGFA, Col2a1 and Biglycan was detected by immunofluorescence. Newly formed cartilage tissues were collected for metabolomics analysis to comprehensively evaluate the mechanism of action of astragalus polysaccharide-containing 3D-printed scaffolds in cartilage repair. <i>Results</i>: The recovery of cartilage defects in the scaffold group was found to be significantly better than that in the model group and comparable to that of the normal group by gross observation, micro-CT, HE and ABH staining. Immunofluorescence results showed that the expression of VEGFA, Col2a1 and Biglycan in the scaffold group was higher than that in the model group (all <i>P</i> < 0.05), comparable to that in the normal group. Metabolomics revealed that 29 metabolites were reversed in the scaffold group, with a reversal rate of 58%. The reversal mainly included groups of phospholipids, sphingolipids, purines, amino acids and energy metabolism-related changes. Fifteen metabolic pathways may be involved, and phospholipid and sphingolipid metabolism, fatty acid metabolism and purine metabolism are the major differential metabolic pathway change groups. <i>Conclusion</i>: Astragalus polysaccharide-containing 3D-printed scaffolds may accelerate cartilage collagen matrix remodeling, correct cartilage tissue metabolic disorders by promoting the expression of vascular-related factors, and ultimately promote cartilage repair.