Biodegradable Dual-Stimuli Hydrogel Scaffoldoid Synergizing Piezoionic and Lithium-Ion Release for Critical-Sized Bone Defect Regeneration

Critical bone defects require interventional treatment as they exceed the body's natural repair capacity. The emerging approaches involve implantable biomaterial or devices, but persist challenges in biodegradability, low cell migration, and differentiation efficiency, complex surgery procedures. This study presents a biodegradable piezoionic hydrogels assembly scaffoldoid composed of piezoelectric glycine-based hydrogel and Li⁺-contained injectable conductive hydrogel. Upon ultrasound stimulation, the piezoelectric hydrogel generates an electric field that propagates through the conductive hydrogel. The regulation of Li⁺ concentration to enhance the electrical conductivity of conductive hydrogels facilitates the recruitment of bone marrow mesenchymal stem cells (BMSCs) by the assembly. Under the synergistic stimulation of electrical signals and Li⁺, namely, dual-stimuli, the recruited BMSCs activated their PI3K/AKT and β-catenin/TCF7/CCN4 signaling pathways, thereby promoting the high expression of osteogenic genes such as RUNX2. Moreover, the conductive hydrogel is injectable, serving as a conformal scaffoldoid for full wound coverage, and the piezoelectric hydrogel can be seamlessly attached upon with the conductive hydrogel at the wound site, thereby simplifying the interventional repair procedures.