Biodegradable piezoelectric PHB-BT nanofiber scaffolds combined with ultrasound stimulation to accelerate bone regeneration by regulating Ca2+/CaN/NFAT

Theranostics. 2026 Jan 22;16(8):4283-4303. doi: 10.7150/thno.124648. eCollection 2026.

Abstract

Rationale: Bone defects pose a persistent challenge in orthopedic medicine due to their limited self-repair capacity. Although guided bone regeneration scaffolds have shown therapeutic potential, their clinical efficacy remains constrained by their suboptimal osteoinductive capability. Methods: Herein, we developed biodegradable piezoelectric polyhydroxybutyrate-barium titanate (PHB-BT) nanofiber scaffolds capable of generating synergistic piezoelectric stimulation for bone repair when integrated with low-intensity pulsed ultrasound (LIPUS). Results: Compared with conventional PHB scaffolds, ​PHB-BT nanofiber scaffolds​ ​showed enhanced piezoelectric properties​ and ​excellent biocompatibility, ​thereby facilitating​ sustained osteogenic activity. ​In vitro​ studies revealed that these scaffolds ​significantly promoted​ the osteogenic differentiation of bone marrow mesenchymal stem cells under LIPUS stimulation. ​Notably, ​in vivo​ evaluations ​demonstrated​ that these scaffolds ​substantially accelerated bone defect repair​, with complete scaffold degradation observed after eight weeks. Mechanistically, PHB-BT nanofibers improved osteogenesis via activating the Ca2+/calcineurin/nuclear factor of activated T-cells signaling pathway in response to ultrasound stimulation. Conclusions: These findings have significant implications for the design of next-generation, implantable electrical stimulators capable of providing sustained electromechanical cues for personalized bone tissue engineering applications.

Keywords: bone defect; electrical stimulation; nanofiber scaffold; piezoelectric effects; ​ osteogenesis.

MeSH terms

  • Animals
  • Barium Compounds* / chemistry
  • Bone Regeneration* / drug effects
  • Calcium / metabolism
  • Cell Differentiation / drug effects
  • Humans
  • Hydroxybutyrates* / chemistry
  • Male
  • Mesenchymal Stem Cells / drug effects
  • NFATC Transcription Factors / metabolism
  • Nanofibers* / chemistry
  • Osteogenesis / drug effects
  • Polyesters* / chemistry
  • Polyhydroxybutyrates
  • Prohibitins
  • Rats
  • Tissue Engineering / methods
  • Tissue Scaffolds* / chemistry
  • Titanium* / chemistry
  • Ultrasonic Waves

Substances

  • Prohibitins
  • Barium Compounds
  • Hydroxybutyrates
  • Titanium
  • barium titanate(IV)
  • NFATC Transcription Factors
  • poly-beta-hydroxybutyrate
  • PHB protein, human
  • Calcium
  • Polyesters
  • Polyhydroxybutyrates