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<p>Intervertebral disc degeneration, the leading cause of chronic low back pain, remains incurable with traditional conservative therapies limited to symptomatic alleviation. We present an ECM-mimetic injectable hydrogel (HPTC) synthesized via dynamic crosslinking of hyaluronic acid-phenylboronic acid (HA-PBA) and tannic acid-cerium(III) metal-polyphenol networks (TA-Ce³⁺ MPNs), which faithfully recapitulates native nucleus pulposus ECM to enable functional tissue regeneration. In vitro, HPTC presented broad-spectrum reactive oxygen species scavenging and downregulated pro-inflammatory cytokine expression (TNF-α, IL-1β, IL-6), while upregulating anti-inflammatory markers (IL-4, IL-10). Crucially, Ce³⁺ effectively reduced dissolved oxygen levels (to 105% vs. 115% in control at 15&#xa0;min), thereby promoting HIF-1α signal expression and mitigating nucleus pulposus cells senescence under H₂O₂-induced oxidative stress. In rat and rabbit intervertebral disc degeneration models, a single, minimally invasive injection of the ECM-mimetic HPTC hydrogel preserved the disc height index and magnetic resonance imaging signal intensity, enhanced aggrecan and collagen II deposition, suppressed inflammatory mediators, and elevated HIF-1α while reducing p21 expression in situ. Transcriptomic analysis further implicated HIF-1α pathways in ECM regeneration. All these findings demonstrate that the HPTC hydrogel leverages metal-polyphenol chemistry within an ECM-inspired framework to synergistically modulate oxygen homeostasis, oxidative stress, and inflammation, offering a bifunctional and biomimetic platform for disc regeneration.</p> Graphical Abstract <p></p>

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An ECM-mimetic hydrogel for disc repair: reconstituting hypoxia and alleviating NPC senescence to halt intervertebral disc degeneration

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月10日

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  • Yifan Wang,
  • Minglang Zou,
  • Junyao Cheng,
  • Cuiping Chen,
  • Chuyue Zhang,
  • Taoxu Yan,
  • Xianzheng Wang,
  • Zheng Tian,
  • Zhenyue Zhang,
  • Kaige Mao,
  • Bo Li,
  • Xuanhui Liu,
  • Haoming Liu,
  • Pengfei Chi,
  • Zhimin Pan,
  • Zuquan Weng,
  • Da Huang,
  • Jianheng Liu,
  • Zheng Wang

摘要

Intervertebral disc degeneration, the leading cause of chronic low back pain, remains incurable with traditional conservative therapies limited to symptomatic alleviation. We present an ECM-mimetic injectable hydrogel (HPTC) synthesized via dynamic crosslinking of hyaluronic acid-phenylboronic acid (HA-PBA) and tannic acid-cerium(III) metal-polyphenol networks (TA-Ce³⁺ MPNs), which faithfully recapitulates native nucleus pulposus ECM to enable functional tissue regeneration. In vitro, HPTC presented broad-spectrum reactive oxygen species scavenging and downregulated pro-inflammatory cytokine expression (TNF-α, IL-1β, IL-6), while upregulating anti-inflammatory markers (IL-4, IL-10). Crucially, Ce³⁺ effectively reduced dissolved oxygen levels (to 105% vs. 115% in control at 15 min), thereby promoting HIF-1α signal expression and mitigating nucleus pulposus cells senescence under H₂O₂-induced oxidative stress. In rat and rabbit intervertebral disc degeneration models, a single, minimally invasive injection of the ECM-mimetic HPTC hydrogel preserved the disc height index and magnetic resonance imaging signal intensity, enhanced aggrecan and collagen II deposition, suppressed inflammatory mediators, and elevated HIF-1α while reducing p21 expression in situ. Transcriptomic analysis further implicated HIF-1α pathways in ECM regeneration. All these findings demonstrate that the HPTC hydrogel leverages metal-polyphenol chemistry within an ECM-inspired framework to synergistically modulate oxygen homeostasis, oxidative stress, and inflammation, offering a bifunctional and biomimetic platform for disc regeneration.

Graphical Abstract