3D-printed shape memory scaffolds from Pickering emulsion for codelivery of exosomes and Mg²⁺ to promote bone regeneration

Repairing critical-sized bone defects, particularly those with irregular geometries, remains a significant clinical challenge. Stem cell-derived exosomes have been shown to promote bone defect repair. However, effective encapsulation and delivery of exosomes are still not well solved. To address this, we developed a composite bioink by encapsulating exosomes within a Pickering emulsion system (Water in oil. Water phase: MgO/exosomes; Oil phase: hydroxyapatite/silica/Poly (D, L-lactide-co-trimethylene carbonate)). This bioink was used to fabricate an exosome-laden MgO composite scaffold (PHS/MgO-EXO) via 3D printing. The PHS/MgO-EXO scaffold featured an excellent hierarchical interconnecting porous structure, capable of sustained release of Mg²⁺ ions and exosomes, which collectively promoted cell proliferation, adhesion, and osteogenic differentiation. Notably, the scaffold exhibited an excellent shape memory effect, enabling it to achieve conformal fitting and repair of irregular defects upon external stimulation. Moreover, the PHS/MgO-EXO scaffold could promote the repair and regeneration of bone defect in rat skull defect experiment. Transcriptome analyses revealed the mechanism: the PHS/MgO-EXO scaffold regulated the osteogenic differentiation of mBMSCs through the Hippo signaling pathways, and promoted tissue regeneration by modulating the immune response through the TNF-α and IL-17 pathways. Taken together, this PHS/MgO-EXO scaffold with shape memory properties can release exosomes and sustain the release of Mg²⁺ ions, which will provide a highly promising strategy for clinical repair of irregular bone defects.