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Advanced Science · 2024 · IF 14.3

Copper-loaded Milk-Protein Derived Microgel Preserves Cardiac Metabolic Homeostasis After Myocardial Infarction

Xiaoqian Hong,Geer Tian,Binyao Dai,Xuhao Zhou,Ying Gao,Lianlian Zhu,Haoran Liu,Qinchao Zhu,Liwen Zhang,Yang Zhu,Daxi Ren,Chengchen Guo,Jinliang Nan,Xianbao Liu,Jian'an Wang,Tanchen Ren

Myocardial Infarction (MI) is a leading cause of death worldwide. Metabolic modulation is a promising therapeutic approach to prevent adverse remodeling after MI. However, whether material-derived cues can treat MI through metabolic regulation is mainly unexplored. Herein, a Cu 2+ loaded casein microgel (CuCMG) aiming to rescue the pathological intramyocardial metabolism for MI amelioration is developed. Cu 2+ is an important ion factor involved in metabolic pathways, and intracardiac copper drain is observed after MI. It is thus speculated that intramyocardial supplementation of Cu 2+ can rescue myocardial metabolism. Casein, a milk-derived protein, is screened out as Cu 2+ carrier through molecular-docking based on Cu 2+ loading capacity and accessibility. CuCMGs notably attenuate MI-induced cardiac dysfunction and maladaptive remodeling, accompanied by increased angiogenesis. The results from unbiased transcriptome profiling and oxidative phosphorylation analyses support the hypothesis that CuCMG prominently rescued the metabolic homeostasis of myocardium after MI. These findings enhance the understanding of the design and application of metabolic-modulating biomaterials for ischemic cardiomyopathy therapy.

研究领域: 心脏病学 · 生物材料 · 代谢工程 · 组织工程
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ADVANCED MATERIALS · 2023 · IF 29.4

Cellular Membrane-Engineered Nanovesicles as Three-Stage Booster to Target Lesion Core

Fanyi Huang,Yawei Du,Yanjia Chen,Zeping Qiu,Zhiyan Wang,Yingze Fan,Yunjing Shi,Zhuojin Li,Ke Yang,Wenguo Cui,Wei Jin

Lesion core is the area with the most serious injury and vigorous repair. Existing nanocarriers are difficult to break through the targeted delivery to lesion core and the precise treatment for intracellular and extracellular microenvironment. Herein, a cellular membrane-engineered nanovesicle (CMEV) with hierarchical structure is constructed using double emulsion-extrusion method, by integrating neutrophil membrane, functional antibody and gelled drug-loaded core, as ‘three-stage booster’ to target the lesion core and deliver catestatin (CST), a small therapeutic peptide, for ischemic cardiomyopathy therapy. By coating neutrophil membrane outside the shell, CMEV is endowed with the function of neutrophil-like migration to achieve the first stage of tissue targeting. Based on the specific anchoring to injured myocardium, myosin light chain 3 (MLC3) antibody was embedded to fulfill the second stage of CMEV accumulation in lesion core. The gelled core containing CST-sodium alginate (NaAlg) with pH-responsive shell is prepared by ionic cross-linking to accomplish the third stage of precise CST administration. Triggered by the microenvironment, NaAlg electrostatically adheres to the lesion core for sustained release, enhancing the efficacy of CST in improving cardiomyocyte apoptosis, excessive fibrosis, macrophage polarization and angiogenesis. Thus, the “three-stage booster” nanovesicle significantly ameliorates cardiac function and adverse remodeling to treat ischemic cardiomyopathy. This article is protected by copyright. All rights reserved

研究领域: 纳米技术 · 药学 · 心脏病学 · 生物材料 · 药物递送系统
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ADVANCED MATERIALS · 2025 · IF 26.8

Melt-Based Embedded Printing of Macroscopically-Conformal, Electro-Conductive and Elastomeric Patches for Improved Myocardial Infarction Repair

Xiangbin Zeng,Zhenlong Li,Xiao Tan,Zhishuo Ren,Jingyuan Gao,Zijie meng,Dichen Li,Jinhai Fan,Mao Mao,Baolin Guo,Jiankang He

Poly(glycerol sebacate) (PGS) is promising for engineering flexible cardiac patches for myocardial infarction repair due to its unique elasticity. However, its insulating nature and complex thermal curing process hinder existing 3D printing techniques from producing patches that recapitulate the mechanical, electrical, and anatomical features of native myocardium. Here, a melt-based embedded printing strategy enabling direct, freeform fabrication of thermosetting PGS architectures with in situ thermal curing is proposed. The viscoelastic matrix enables high-fidelity extrusion of PGS prepolymer into microscale filaments while providing temporary support for in situ curing of PGS elastomeric architectures with seamless interface fusion and mechanical stability. This platform further allows direct printing of electro-conductive cardiac patches using carbon nanotube-incorporated PGS that mimic ventricular curvature and mechanical anisotropy. Compared to pure PGS controls, the electro-conductive patches enhance cardiomyocyte maturation in vitro, evidenced by improved sarcomere organization, calcium handling, and electrical synchronization. In vivo, these acellular patches improve mechanical integration with host myocardium, promote vascularization, reduce inflammation, and preserve cardiomyocyte survival, collectively maintaining ejection fraction and attenuating adverse remodeling. This work, therefore, establishes a generalizable manufacturing strategy for printing thermosetting elastomeric constructs with integrated conductivity as acellular, mechanically and electrically functional patches for structural cardiac repair.

研究领域: 生物医学工程 · 心脏组织工程 · 3D打印 · 生物材料 · 再生医学 · 柔性电子 · 高分子科学
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