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<p>Silk fibroin scaffolds (SFCs) that exploit piezoelectricity for osteochondral repair have been hampered by both insufficient electromechanical output and a pro‑inflammatory joint microenvironment that erodes therapeutic efficacy. To overcome these barriers, we developed an intra‑articular implantable scaffold with enhanced piezoelectricity, called FENS@MF, via covalently integrating ultradispersible magnetic nanoparticles (MNPs) into SFCs via EDC/NHS crosslinking. Under magnetically controlled stimulation, FENS@MF generates an ~ 8.5‑fold increase in output voltage, a threefold enhancement in tensile strength, and undergoes only 15.65% degradation by protease XIV over 15 d, thereby sustaining potent electromechanical signaling. In vitro, it markedly upregulates chondrogenic (COL2, SOX9), osteogenic (RUNX2, BMP2), and angiogenic (VEGF, eNOS) markers, while inducing M1‑to‑M2 macrophage polarization to attenuate inflammation. In rat osteochondral defect models, FENS@MF outperforms conventional SFC and FENS scaffolds, achieving cartilage and subchondral bone regeneration with bone mineral density and trabecular thickness comparable to autologous grafts. FENS@MF enhances the piezoelectric effect by responding to the magnetic field (MF) and absorbing electromagnetic waves, and cooperates with magnetic stimulation and immune microenvironment regulation to achieve efficient osteochondral regeneration. Enhanced piezoelectric signals may drive SOX9-mediated chondrogenesis through activation of p38 MAPK phosphorylation (upregulation of COL2/ACAN) and trigger osteogenic differentiation through β-catenin nuclear translocation (upregulation of RUNX/BMP2).This study is the first to integrate the piezoelectric effect, magnetic stimulation and immunomodulation, which breaks through the limitation of a single functional scaffold, establishes a ‘structure-function-signal’ paradigm for intelligent osteochondral repair, and provides a multifunctional platform for functional tissue regeneration.</p>

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Piezoelectric scaffold with enhanced effect drives the healing of osteochondral defects through electromechanical-immune coupling

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月9日

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  • Xin Liu,
  • Congyang Xue,
  • Jun Guo,
  • Nan Chen,
  • Bo Chen,
  • Zihan Wang,
  • Xuan Han,
  • Liping Chen,
  • Tian Tang,
  • Nan Wang,
  • Jun Gu,
  • Ding Qu,
  • Ran Kang

摘要

Silk fibroin scaffolds (SFCs) that exploit piezoelectricity for osteochondral repair have been hampered by both insufficient electromechanical output and a pro‑inflammatory joint microenvironment that erodes therapeutic efficacy. To overcome these barriers, we developed an intra‑articular implantable scaffold with enhanced piezoelectricity, called FENS@MF, via covalently integrating ultradispersible magnetic nanoparticles (MNPs) into SFCs via EDC/NHS crosslinking. Under magnetically controlled stimulation, FENS@MF generates an ~ 8.5‑fold increase in output voltage, a threefold enhancement in tensile strength, and undergoes only 15.65% degradation by protease XIV over 15 d, thereby sustaining potent electromechanical signaling. In vitro, it markedly upregulates chondrogenic (COL2, SOX9), osteogenic (RUNX2, BMP2), and angiogenic (VEGF, eNOS) markers, while inducing M1‑to‑M2 macrophage polarization to attenuate inflammation. In rat osteochondral defect models, FENS@MF outperforms conventional SFC and FENS scaffolds, achieving cartilage and subchondral bone regeneration with bone mineral density and trabecular thickness comparable to autologous grafts. FENS@MF enhances the piezoelectric effect by responding to the magnetic field (MF) and absorbing electromagnetic waves, and cooperates with magnetic stimulation and immune microenvironment regulation to achieve efficient osteochondral regeneration. Enhanced piezoelectric signals may drive SOX9-mediated chondrogenesis through activation of p38 MAPK phosphorylation (upregulation of COL2/ACAN) and trigger osteogenic differentiation through β-catenin nuclear translocation (upregulation of RUNX/BMP2).This study is the first to integrate the piezoelectric effect, magnetic stimulation and immunomodulation, which breaks through the limitation of a single functional scaffold, establishes a ‘structure-function-signal’ paradigm for intelligent osteochondral repair, and provides a multifunctional platform for functional tissue regeneration.