Bioactive Decellularized Extracellular Matrix Platform Integrating Multifunctional Nanozymes and Cell-Laden Microgels for Acute Liver Failure Treatment

作者：Xiaodie Chen, Jiabin Zhang, Tong Lin, Feng Zhou, Fenfang Li, Tiantian Xue, Qingguo Zhong, Wei‐Jen Lee, Guipan Chen, Haixia Wang, Enguo Ju, Mingqiang Li, Yu Tao · 发表于：ACS Nano · 年份：2025 · DOI：10.1021/acsnano.4c13709 · 被引用次数：21 · 研究领域：Graphene and Nanomaterials Applications、Advanced Nanomaterials in Catalysis、Tissue Engineering and Regenerative Medicine

Mesenchymal stem cell (MSC) therapy has emerged as a promising alternative approach for treating acute liver failure (ALF) while confronting the shortage of low efficiency and poor engraftment within a hostile liver milieu. In this study, we establish a bioactive decellularized extracellular matrix (dECM) platform that incorporates dihydrolipoic acid (DHLA)-protected Pt nanoclusters doped with Cu (PtCu-DHLA) nanozymes and cell-laden microgels. The PtCu-DHLA nanozymes, selected for their versatility, function as antioxidant, anti-inflammatory, pro-proliferative, and pro-angiogenic agents, enhancing ALF alleviation and providing an optimal microenvironment for MSC transplantation. Additionally, a methacrylic anhydride (MA)-modified porcine liver-derived decellularized extracellular matrix (PLdECM) hydrogel (PLdECMMA) has been developed for the construction of microgels via microfluidic devices. Interferon γ (IFNγ) preconditioned MSCs encapsulated in PLdECMMA microgels exhibit enhanced immunomodulating activity and prolonged survival. PtCu-DHLA nanozymes and cell-laden microgels are codelivered by leveraging the PLdECM hydrogel for orthotopic transplantation. The transplanted dECM platform enables an efficient and successful rescue of CCl 4 -induced ALF by counteracting oxidative stress, suppressing inflammatory storms, and promoting cellular regeneration. Overall, this study highlights a synergistic and reinforced strategy that combines biomimetic nanozymes with MSC therapy, of...