Biomimetic Barium Titanate/PLA Scaffold with Shape Memory and Bioelectro-Active Capacities Promotes Bone Regeneration

Shiyan Lv,1,* Yuechi Zhang,2,* Xiongjie Liang,1,* Wenbo Xu,1 Zhibin Geng,1 Weifeng Hu,1 Xiaoyan Wang,1 Helin Li,1 Wenhui Guo,1 Yongbin Jing,1 Xiaoqi Liu,1 Huichao Fu,1 Gongping Xu,1 Chunyang Xi,1 Jinglong Yan,1 Hui Chi1 1Department of Orthopedic Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, 150086, People’s Republic of China; 2Department of Astronautical Science and Mechanics, Harbin Institute of Technology (HIT), Harbin, 150001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinglong Yan; Hui Chi, Email [email protected]; [email protected]: Bone, a natural piezoelectric material, converts mechanical stress to electrical signals; local bioelectric changes in defects affect repair. Current biomimetic bone materials focus on composition, bioactivity and structure, neglecting bioelectric effects. Piezoelectric materials reconstruct electrical microenvironments, simulating natural regulation and addressing traditional materials’ structural reliance, offering effective repair strategies.Methods: In this study, barium titanate piezoelectric nanoceramic particles were embedded into thermoresponsive shape-memory polylactic acid via 4D printing to fabricate BT/PLA composite scaffolds. The scaffolds were characterized using scanning electron microscopy, X-ray diffraction, surface roughness analysis, water contact angle measurement, as well as mechanical and piezoelectric property tests. Cellular experiments were performed to verify the effects of these scaffolds on the proliferation, adhesion, and osteogenic capacity of bone marrow mesenchymal stem cells under low-intensity pulsed ultrasound stimulation. Additionally, a rat calvarial defect model was established to evaluate the in vivo bone repair efficacy of the scaffolds.Results: A shape-memory piezoelectric BT/PLA scaffold was 4D-printed. The 20 wt% BT scaffold showed excellent mechanics (~25 MPa compressive strength) and shape memory (full recovery in 5s), meeting clinical needs. All scaffolds were non-cytotoxic; BT/PLA with LIPUS generated ~1 μA current, promoting BMSC proliferation and osteogenesis. BT/PLA + LIPUS showed superior in vivo bone formation in rats, validating clinical potential for critical defects.Conclusion: The BT/PLA scaffold, combining shape-memory and piezoelectric effects, shows significant bone regeneration potential. Its degradability with 4D printing may facilitate translation of personalized bone repair implants from bench to bedside. Transcriptome sequencing suggests its osteogenic effect may involve the PI3K-Akt pathway, providing a basis for optimizing molecular targets in future bone regenerative materials and reinforcing the study’s scientific value in material design and mechanistic exploration. Keywords: 4D-printing, bone regeneration, electric stimulation, piezoelectric scaffolds, shape memory