<p>Intervertebral disc degeneration (IVDD) is driven by severe oxidative stress, a loss of extracellular matrix (ECM) homeostasis, and ferroptosis of nucleus pulposus cells (NPCs) as a core pathological mechanism. Therapeutic strategies based on microenvironment engineering that can simultaneously combat oxidative damage and promote tissue repair are urgently needed. Here, we reestablish the IVDD microenvironment using a dual-function nanogel, which integrates a catalytic 2D Mo₂C MXene within a supramolecular Collagen II-mimetic matrix formed by a GFOGER-functionalized self-assembling peptide hydrogel (SAPH). The function of clearing oxidative stress be attribute to the catalytic Mo₂C MXene and the SAPH-R<sub>16</sub>GFOGER serving as an effective local depot, which to preserve mitochondrial integrity and dismantle the ferroptotic program. Concurrently, the SAPH-R<sub>16</sub>GFOGER mimic Collagen II matrix to promoting NPC adhesion and proliferation, upregulating the synthesis of new ECM, and shifting the cellular phenotype from catabolic to anabolic. It is notable that in a rat IVDD model, this dual-function engineering strategy effectively mitigated oxidative stress, preserved disc height and hydration, and restored the native ECM-rich architecture of the nucleus pulposus. This work presents a synergistic microenvironment engineering strategy, demonstrating that the integration of an antioxidant MXene within a biomimetic matrix is a promising platform for attenuating degenerative diseases.</p> Graphical abstract <p></p>

错误:搜索内容不能为空,请输入英文关键词
错误:关键词超出字数限制,请精简
高级检索

Synergistic microenvironment therapy: a dual-function nanogel of supramolecular collagen ll-mimetic matrix and antioxidant MXene for attenuating intervertebral disc degeneration

  • Gan Lyu,
  • Zhan Gao,
  • Zhuoyi Cao,
  • Qiwei Zhou,
  • Yuli Chen,
  • Shu Yang,
  • Haibo Liang,
  • Xun Lu,
  • Sunlong Li,
  • Xinzhou Wang,
  • Shuai Sun,
  • Xiaoqing Gao,
  • Yunlong Zhou,
  • Aimin Wu,
  • Xiaolin Zhou,
  • Xiangyang Wang

摘要

Intervertebral disc degeneration (IVDD) is driven by severe oxidative stress, a loss of extracellular matrix (ECM) homeostasis, and ferroptosis of nucleus pulposus cells (NPCs) as a core pathological mechanism. Therapeutic strategies based on microenvironment engineering that can simultaneously combat oxidative damage and promote tissue repair are urgently needed. Here, we reestablish the IVDD microenvironment using a dual-function nanogel, which integrates a catalytic 2D Mo₂C MXene within a supramolecular Collagen II-mimetic matrix formed by a GFOGER-functionalized self-assembling peptide hydrogel (SAPH). The function of clearing oxidative stress be attribute to the catalytic Mo₂C MXene and the SAPH-R16GFOGER serving as an effective local depot, which to preserve mitochondrial integrity and dismantle the ferroptotic program. Concurrently, the SAPH-R16GFOGER mimic Collagen II matrix to promoting NPC adhesion and proliferation, upregulating the synthesis of new ECM, and shifting the cellular phenotype from catabolic to anabolic. It is notable that in a rat IVDD model, this dual-function engineering strategy effectively mitigated oxidative stress, preserved disc height and hydration, and restored the native ECM-rich architecture of the nucleus pulposus. This work presents a synergistic microenvironment engineering strategy, demonstrating that the integration of an antioxidant MXene within a biomimetic matrix is a promising platform for attenuating degenerative diseases.

Graphical abstract