Abstract
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(16)GFOGER serving as an effective local depot, which to preserve mitochondrial integrity and dismantle the ferroptotic program. Concurrently, the SAPH-R(16)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.