Tong Junran, Sun Di, Sun Jinpeng, Zhang Jiahui, Chen Meiyi, Liu Xiangfei, Zhang Ruiyu, Zhang Fangyuan, Zheng Chuansheng, Wei Yumiao, Guo Xiaopeng
Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Mater Today Bio. 2025 Nov 19;35:102556. doi: 10.1016/j.mtbio.2025.102556. eCollection 2025 Dec.
Myocardial infarction (MI) is often accompanied by irreversible cardiomyocyte damage and limited tissue regeneration, posing a persistent challenge in clinical practice. In the early phase of MI, a burst of reactive oxygen species (ROS) and the resulting pro-inflammatory feedback loop lead to disruption of the myocardial microenvironment, immune dysregulation, and ultimately, impaired repair. Therefore, early clearance of ROS, inhibition of pro-inflammatory responses, and immune modulation toward a reparative phenotype are essential for effective intervention.To address this, we developed an intelligent, stimuli-responsive polyvinyl alcohol (PVA)-based hydrogel incorporating multifunctional MXene nanozymes for the localized and controllable delivery of 4-octyl itaconate (4-OI) to infarcted cardiac tissue. This system exhibits excellent fluidity, injectability, and in situ forming ability, enabling stable encapsulation and controlled release of 4-OI@MXene. Moreover, the mild reductive activity of MXene contributes to the creation of a more favorable microenvironment for tissue repair.Mechanistically, the hydrogel system activates the AMPK-Nrf2-Keap1 signaling axis to efficiently scavenge excessive ROS, while simultaneously suppressing NF-κB-mediated inflammation and promoting macrophage polarization toward the M2 phenotype. These coordinated effects substantially improve the oxidative and immune microenvironment post-MI, thereby facilitating myocardial repair and functional recovery.To our knowledge, this is the first study n the context of myocardial infarction to propose a synergistic activation of AMPK and Nrf2 signaling within a 4-OI@MXene-PVA hydrogel platform, offering a promising strategy for precise intervention and regenerative therapy following MI.
心肌梗死（MI）常伴有不可逆的心肌细胞损伤和有限的组织再生，这在临床实践中一直是个挑战。在MI的早期阶段，活性氧（ROS）的爆发以及由此产生的促炎反馈环会导致心肌微环境破坏、免疫失调，并最终损害修复。因此，早期清除ROS、抑制促炎反应以及将免疫调节为修复表型对于有效干预至关重要。为了解决这个问题，我们开发了一种智能的、刺激响应性的基于聚乙烯醇（PVA）的水凝胶，其中包含多功能MXene纳米酶，用于将衣康酸4-辛酯（4-OI）局部可控地递送至梗死心肌组织。该系统具有出色的流动性、可注射性和原位形成能力，能够稳定封装和控制释放4-OI@MXene。此外，MXene的温和还原活性有助于为组织修复创造更有利的微环境。从机制上讲，水凝胶系统激活AMPK-Nrf2-Keap1信号轴以有效清除过量的ROS，同时抑制NF-κB介导的炎症并促进巨噬细胞向M2表型极化。这些协同作用显著改善了MI后的氧化和免疫微环境，从而促进心肌修复和功能恢复。据我们所知，这是心肌梗死背景下第一项提出在4-OI@MXene-PVA水凝胶平台内协同激活AMPK和Nrf2信号的研究，为MI后的精确干预和再生治疗提供了一种有前景的策略。
