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<p>In situ tissue-engineered heart valves (TEHVs) present significant potential to address critical limitations of conventional replacements: suboptimal hemo-compatibility in mechanical valves and compromised durability in bio-prosthetic valves, alongside their inherent inability to support growth and regeneration. However, current research predominantly employs single-scale fiber-based scaffolds with a focus on short-term outcomes, facing challenges in long-term mechanical instability and pathological remodeling. Herein, we propose an innovative mechano-immunological strategy to engineer a multiscale all-fiber TEHV scaffold, spanning drug-loaded polymer nanofibers to integrated “1D yarn–2D fabric–3D valve” via stepwise conjugate electrospinning–weaving–thermoforming assembly. Mechanical testing confirms that the hierarchically interlocked architecture exhibits excellent interfacial stability, anti-contraction capability, bending compliance, and wrinkle recovery at 1D/2D scales. The resultant 3D valve demonstrates ISO 5840-compliant hemodynamic performance while maintaining functional stability during progressive leaflet thickening. In vitro/in vivo biological evaluations further validate biosafety and concurrent functionalities: fibrotic capsule resistance, suppression of α-SMA-dominant pathological fibrosis, and M2 macrophage-polarization-driven anti-inflammatory remodeling. Collectively, this mechano-immunological combination strategy provides a potential pathway toward sustaining functional homeostasis in preclinical TEHV development.</p> Graphical Abstract <p></p>

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A Mechano-Immunological Combination Strategy for In Situ Heart Valve Regeneration via a Multiscale All-Fiber Scaffold

  • 期刊论文

  • 发表日期：

    2026年2月9日

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  • Shiping Chen,
  • Gaowei Zhu,
  • Xiaofan Zheng,
  • Leqian Wei,
  • Yajuan Wang,
  • Shengzhang Wang,
  • Fan Zhao,
  • Fujun Wang,
  • Ze Zhang,
  • Jifu Mao,
  • Lu Wang

摘要

In situ tissue-engineered heart valves (TEHVs) present significant potential to address critical limitations of conventional replacements: suboptimal hemo-compatibility in mechanical valves and compromised durability in bio-prosthetic valves, alongside their inherent inability to support growth and regeneration. However, current research predominantly employs single-scale fiber-based scaffolds with a focus on short-term outcomes, facing challenges in long-term mechanical instability and pathological remodeling. Herein, we propose an innovative mechano-immunological strategy to engineer a multiscale all-fiber TEHV scaffold, spanning drug-loaded polymer nanofibers to integrated “1D yarn–2D fabric–3D valve” via stepwise conjugate electrospinning–weaving–thermoforming assembly. Mechanical testing confirms that the hierarchically interlocked architecture exhibits excellent interfacial stability, anti-contraction capability, bending compliance, and wrinkle recovery at 1D/2D scales. The resultant 3D valve demonstrates ISO 5840-compliant hemodynamic performance while maintaining functional stability during progressive leaflet thickening. In vitro/in vivo biological evaluations further validate biosafety and concurrent functionalities: fibrotic capsule resistance, suppression of α-SMA-dominant pathological fibrosis, and M2 macrophage-polarization-driven anti-inflammatory remodeling. Collectively, this mechano-immunological combination strategy provides a potential pathway toward sustaining functional homeostasis in preclinical TEHV development.

Graphical Abstract