(227c) 3D Printed Self-Powered Piezoelectric Smart Scaffolds for Enhanced Bone Tissue Regeneration

Piezoelectricity in native bones has been recognized as a key factor in bone regeneration. Piezoelectric materials can mimic this effect by providing electrical stimulation that recruits host cells, enhances osteogenic differentiation, and promotes mineralization. To further strengthen their regenerative potential, calcium phosphate (CaP) is often incorporated to support osteoconductivity and stimulate the secretion of endogenous bone-growth factors, thereby creating a beneficial osteogenic microenvironment. Nevertheless, conventional fabrication methods face significant challenges in producing personalized piezoelectric scaffolds with both functional and structural precision. Extrusion based three-dimensional (3D) printing uses layer-by-layer deposition to customize scaffold geometry and induces molecular chain alignment through heating and stretching during extrusion, which promotes the formation of the β-phase crystalline structure and enhances piezoelectricity (Figure A). In this study, we developed 3D printed piezoelectric smart scaffolds composed of poly(L-lactic acid) (PLLA) blended with β-tricalcium phosphate (β-TCP) by extrusion-based 3D printing, with a uniform pore size of ~200 μm with high interconnectivity (Figure B & C). These 3D printed piezoelectric smart scaffolds can be remotely activated by ultrasound to promote bone regeneration through the synergistic effects of piezoelectric self-charging and the osteo-inductive ions (e.g.,Ca²⁺ and PO₄³⁻) released during β-TCP degradation.

In vitro studies demonstrated that rat bone marrow–derived mesenchymal stem cells (BMSCs) exhibited enhanced osteogenic differentiation when cultured on the piezoelectric smart scaffolds under ultrasound stimulation. Cell proliferation progressively increased on days 1, 3, and 5 (Figure D). After 7 days of ultrasound stimulation, qPCR analysis revealed upregulated expression of key osteogenic genes, including runt-related transcription factor 2 (Runx2), collagen type I alpha 1 (COLIa1), and alkaline phosphatase (ALP) (Figure E). Alkaline phosphatase activity was significantly elevated at both 7 and 14 days, indicating early osteoblast lineage commitment. At later stages, alizarin red staining (ARS) demonstrated extensive calcium deposition and mineralized nodule formation at 14 and 21 days, confirming enhanced extracellular matrix mineralization (Figure F). Current research involves assessing the 3D-printed piezoelectric smart scaffolds' long-term bioactivity in promoting important regenerative processes including angiogenesis and cell migration, as well as how well they function in a model of calvarial defects.

In summary, 3D-printed piezoelectric smart scaffolds exhibited enhanced piezoelectric responsiveness and biological activity, thereby promoting osteogenesis both in vitro and in vivo. This study demonstrates that the integration of piezoelectric scaffolds with ultrasound stimulation provides a self-powered and bioactive platform, offering great promise for accelerating bone regeneration in orthopedic defects.