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

Abstract

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.

Keywords

Tissue engineering heart valve / Nanofiber yarn / Mechanically interlocking / Hemodynamics / Anti-fibrosis / Immunoregulation

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Funding

the National Natural Science Foundation of China(32371402)

the fundamental research project of CNTAC(J202104)

the 111 Project(BP0719035)

the Fundamental Research Funds for the Central Universities and Graduate Student Innovation Fund of Donghua University(CUSF-DH-D-2023023)

the Fundamental Research Funds for the Central Universities(2232024G-01)

RIGHTS & PERMISSIONS

Donghua University, Shanghai, China