Small intestine submucosa decorated 3D printed scaffold accelerated diabetic bone regeneration by ameliorating the microenvironment

The 3D printed scaffolds constructed from polymers have shown significant potential in the field of bone defect regeneration. However, the efficacy of these scaffolds can be markedly reduced in certain pathological conditions like diabetes, where an altered inflammatory microenvironment and diminished small blood vessels complicate the integration of these polymers with the host tissue. In this study, the bioactivity of a 3D-printed poly(lactide- co -glycolide) (PLGA) scaffold is enhanced through the integration of hydroxyapatite (HA), icariin (ICA), and small intestine submucosa (SIS), a form of decellularized extracellular matrix (dECM). The decoration of SIS on the 3D-printed PLGA/HA/ICA scaffold not only improves the mechanical and degradative performance, but also extends the release of ICA from the scaffold. Both in vitro and in vivo studies demonstrate that this functionalized scaffold mitigates the persistent inflammatory conditions characteristic of diabetic bone defects through inducing macrophages towards the M2 phenotype. Additionally, the scaffold promotes angiogenesis by enhancing the migration and tube formation of vascular cells. Furthermore, the synergistic effects of ICA and SIS with the HA scaffolds contribute to the superior osteogenic induction capabilities. This functionalization approach holds significant promise in advancing the treatment of bone defects within the diabetic population, paving a step forward in the application of polymer-based 3D printing technologies in regenerative medicine. 3D-printed PLGA/hydroxyapatite/icariin scaffolds with small intestine submucosa coating offer immunoregulatory abilities, enhance angiogenesis and osteogenesis, and show promise for treating bone defects in diabetic patients.