2. Academic Validation
  3. Bioinspired Engineering of Streamlined Skeletal Interoception: Neural Bioprinted Piezoelectric Scaffolds for Neuro-Vascularized Bone Regeneration

Bioinspired Engineering of Streamlined Skeletal Interoception: Neural Bioprinted Piezoelectric Scaffolds for Neuro-Vascularized Bone Regeneration

  • Adv Sci (Weinh). 2026 Apr;13(21):e24181. doi: 10.1002/advs.202524181.
Yingze Su 1,  Haomin Wang 2,  Weixi Liu 1,  Kangming Chen 3,  Yiyang Min 4,  Jinbo Zhu 1,  Xueyang Li 5,  Anning Su 6,  Hao Yang 7,  Lei Yang 8,  Yun Ji 9,  Yuxin Zhang 10,  Jisi Zheng 10,  Chi Yang 10,  Chuanglong He 8,  Tao Li 1,  Shuo Chen 8,  Tao Wu 11,  Xiaodong Chen 1
Affiliations

Affiliations

  • 1 Department of Orthopaedics, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
  • 2 State Key Lab of Tropic Ocean Engineering Materials and Materials Evaluation, Hainan University, Haikou, People's Republic of China.
  • 3 Department of Orthopaedics, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.
  • 4 Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
  • 5 Department of Orthopaedics, the Second Hospital of Dalian Medical University, Dalian, People's Republic of China.
  • 6 Department of Biomedical Engineering, University of Shanghai for Science and Technology, Shanghai, People's Republic of China.
  • 7 Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
  • 8 State Key Laboratory of Advanced Fiber Materials, College of Biological Science and Medical Engineering, Donghua University, Shanghai, People's Republic of China.
  • 9 Department of Pain Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
  • 10 Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
  • 11 Shanghai University of Medicine & Health Sciences, Shanghai, People's Republic of China.
PMID: 41691467 DOI: 10.1002/advs.202524181
Abstract

The skeletal interoception system that orchestrates bone homeostasis and regeneration through a coordinated "afferent-integration-efferent" reflex arc has been overlooked in bone tissue engineering. The dorsal root ganglion (DRG) neurons constitute the hubs of this system. Moreover, beyond their canonical role within the interoceptive pathway, these neurons exert a direct effector role by secreting Calcitonin gene-related peptide (CGRP) to promote bone repair. However, current sensory nerve-targeted strategies in bone tissue engineering remain static, bypassing the dynamic reflex arc and failing to establish an autonomous functional system. To address this, a streamlined interoception unit was engineered using neural bioprinting of DRG neurons within piezoelectric scaffolds. Upon sensing ultrasound (US) stimulation, the piezoelectric poly(l-lactide) (PLLA) component mediates mechanoelectrical coupling, triggering a CA2 + influx-induced effector response in the incorporated DRG neurons that enhances CGRP secretion and expression. The secreted CGRP subsequently promotes osteogenesis and angiogenesis in vitro and accelerates neuro-vascularized bone regeneration in a rat femoral condyle defect model. This study established a bioinspired platform with a self-contained "sensor-effector" circuit, offering a novel engineered strategy for bone regeneration.

Keywords

3D printing; bone regeneration; calcitonin gene‐related peptide; piezoelectric biomaterials; sensory nerve.

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