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<p>The regeneration of articular cartilage is challenged by local avascularity and mechanically inferior neo-fibrocartilagenesis. While electrical stimulations promote chondrogenesis, their therapeutic application is limited by signal delivery issues and cytotoxicity. Conductive polymer hydrogels, though beneficial, cause inflammation and mechanical mismatch due to non-degradability. Herein, we reported an innovative strategy for the hyaline cartilagenesis of mesenchymal stem cells (MSCs) within a conductive Gelatin methacryloyl/Polydopamine-Polyaniline-Graphene Oxide (GelMA/PDA-PAni-GO) hydrogel under programmed electrical stimulation (PES). The electro-primed MSCs were harvested and re-encapsulated into a non-conductive, benign GelMA hydrogel for implantation. This approach decoupled the programmed ES phase from the implantation phase. In a rat articular cartilage defect model, re-encapsulated PES-MSCs generated hyaline neocartilage with a native-like mechanical property and significantly enhanced defect repair outcomes compared to those in permanent GelMA/PDA-PAni-GO hydrogel, as supported by finite element analysis. Collectively, this study establishes a novel paradigm of “electro-priming and benign implantation” for achieving functional hyaline cartilage regeneration, offering a clinically viable pathway to synergize biophysical cues and stem cell therapy.</p>

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Decoupling electro-priming from implantation enables functional hyaline chondrogenesis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月21日

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  • Zhijun Yu,
  • Xinning Yu,
  • Yu Yan,
  • Jiayu Chen,
  • Wangsiyuan Teng,
  • Minjun Yao,
  • Jinfeng Zhou,
  • Yu Zhang,
  • Haibin Xiang,
  • Zhiyi Wang,
  • Bin Shi,
  • Liang Chen,
  • Xiaoqiang Jin

摘要

The regeneration of articular cartilage is challenged by local avascularity and mechanically inferior neo-fibrocartilagenesis. While electrical stimulations promote chondrogenesis, their therapeutic application is limited by signal delivery issues and cytotoxicity. Conductive polymer hydrogels, though beneficial, cause inflammation and mechanical mismatch due to non-degradability. Herein, we reported an innovative strategy for the hyaline cartilagenesis of mesenchymal stem cells (MSCs) within a conductive Gelatin methacryloyl/Polydopamine-Polyaniline-Graphene Oxide (GelMA/PDA-PAni-GO) hydrogel under programmed electrical stimulation (PES). The electro-primed MSCs were harvested and re-encapsulated into a non-conductive, benign GelMA hydrogel for implantation. This approach decoupled the programmed ES phase from the implantation phase. In a rat articular cartilage defect model, re-encapsulated PES-MSCs generated hyaline neocartilage with a native-like mechanical property and significantly enhanced defect repair outcomes compared to those in permanent GelMA/PDA-PAni-GO hydrogel, as supported by finite element analysis. Collectively, this study establishes a novel paradigm of “electro-priming and benign implantation” for achieving functional hyaline cartilage regeneration, offering a clinically viable pathway to synergize biophysical cues and stem cell therapy.