Immunoregulatory Nanofiber Patches with Locally Activated Delivery of ECM-Producing Drugs Improve Repair in an Intervertebral Disc Herniation Model

Abstract

Conventional microdiscectomy for intervertebral disc herniation (IVDH) effectively alleviates pain but fails to regenerate the annulus fibrosus (AF), resulting in an elevated risk of recurrent herniation and permanent disability. Moreover, the absence of reparative intervention, combined with aging-related inflammation, can exacerbate disc deterioration and degeneration. In this study, single-cell RNA-sequencing analysis revealed distinct cellular profiles in aging IVDH patients, which revealed marked reductions in both the cellular abundance and differentiation potential of senescent annulus fibrosus stem cells (AFSCs). To address this clinical need, we developed a parallel-oriented magnesium silicate (MgSiO₃) nanofiber patch (P-MgSi@TAT) for AF repair. The patch utilizes tannic acid (TA) to reversibly bind to transforming growth factor-β3 (TGF-β3). The sandwich-like structure of MgSiO₃—composed of two Si‒O tetrahedral layers and a Mg²⁺ layer—promotes the release of Mg²⁺–TA–TGF-β3 in an acidic inflammatory microenvironment. In vitro, the parallel fiber architecture exhibited significant anti-inflammatory properties and promoted M2 macrophage polarization via the TGF-β/YAP/TAZ signaling pathway. In addition, the cascade effect triggered by anti-inflammatory cytokines contributes to the alleviation of AFSCs senescence and extracellular matrix (ECM) metabolism homeostasis. In vivo, P-MgSi@TAT supported ECM formation and restored biomechanical properties, thereby facilitating AF regeneration. Thus, this patch holds promise as a therapeutic strategy for AF regeneration, with the potential to reduce recurrent herniation risk, and warrants further clinical trials.

Keywords

Intervertebral disc herniation / Aging rejuvenation / Topography-mediated immunoregulatory / Inflammatory microenvironment-activated drug delivery / Cascade effect

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Funding

the Special Fund for Leading Talent in Mount Tai of Shandong Province (NO.tscx202312075)

the Instrument Improvement Funds of Shandong University(ts20240102)

the Special Foundation for Taishan Scholars(tstp20240853)

RIGHTS & PERMISSIONS

Donghua University, Shanghai, China