HydroWrap治疗t2dm相关骨折：智能h2s输送控制器调节巨噬细胞衰老

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials Pub Date : 2025-05-14 DOI:10.1016/j.bioactmat.2025.05.007

Siqi Zhang , Hannan Cui , Jing Wang , Jie Zhou , Hongli Chen , Xinli Wang , Qian Yang , Jiahao Cao , Kaili Hao , Shanshan Fu , Wuyang Zhang , Xu Wang , Xinsen Lin , Xiqing Sun , Wei Lei , Tengjiao Wang , Yafei Feng

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引用次数: 0

摘要

2型糖尿病（T2DM）骨折愈合受损带来了重大的临床挑战，主要是由于衰老巨噬细胞及其放大效应驱动的骨微环境受损。硫化氢（H2S）水平的降低是这种病理的关键因素。为了解决这个问题，我们开发了HydroWrap，一种先进的h2s递送控制器，旨在调节巨噬细胞衰老的不同阶段。在近红外（NIR）照射下，HydroWrap温度升高，导致水凝胶网络收缩，加速H2S生成。这种快速递送恢复H2S水平，减轻线粒体功能障碍，抑制衰老相关分泌表型（SASP），从而中断衰老级联。在T2DM的高血糖骨微环境中，HydroWrap提供持续的葡萄糖响应性H2S释放，促进线粒体自噬，防止巨噬细胞衰老进程。这种双重机制解决了与衰老相关的急性和慢性功能障碍。体内研究表明，HydroWrap通过缩短恢复时间和提高骨质量显著改善骨折愈合。这些发现强调了使用生物相容性药物输送系统调节T2DM巨噬细胞衰老的治疗潜力。HydroWrap为改善糖尿病患者骨折预后提供了一种有希望的策略，并可能在衰老相关疾病中有更广泛的应用。

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HydroWrap for T2DM-Related Fractures: A smart H2S-delivery controller modulating Macrophage senescence

Impaired fracture healing in type 2 diabetes mellitus (T2DM) poses a significant clinical challenge, primarily due to a compromised bone microenvironment driven by senescent macrophages and their amplifying effects. Reduced hydrogen sulfide (H₂S) levels are a critical contributor to this pathology. To address this, we developed HydroWrap, an advanced H₂S-delivery controller designed to modulate distinct stages of macrophage senescence. Under near-infrared (NIR) irradiation, HydroWrap underwent an increase in temperature, causing the hydrogel network to contract and accelerate H₂S generation. This rapid delivery restores H₂S levels, alleviating mitochondrial dysfunction and suppressing senescence-associated secretory phenotypes (SASP), thereby interrupting the senescence cascade. In T2DM's hyperglycemic bone microenvironment, HydroWrap provides sustained, glucose-responsive H₂S release, promoting mitophagy and preventing macrophage senescence progression. This dual mechanism addresses both acute and chronic dysfunctions associated with senescence. In vivo studies demonstrated that HydroWrap significantly improved fracture healing by reducing recovery time and enhancing bone quality. These findings underscore the therapeutic potential of modulating macrophage senescence in T2DM using a biocompatible drug delivery system. HydroWrap offers a promising strategy for improving fracture outcomes in diabetic patients and may hold broader applications in senescence-related diseases.

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来源期刊

Bioactive Materials Biochemistry, Genetics and Molecular Biology-Biotechnology

CiteScore

28.00

自引率

6.30%

发文量

436

审稿时长

20 days

期刊介绍： Bioactive Materials is a peer-reviewed research publication that focuses on advancements in bioactive materials. The journal accepts research papers, reviews, and rapid communications in the field of next-generation biomaterials that interact with cells, tissues, and organs in various living organisms. The primary goal of Bioactive Materials is to promote the science and engineering of biomaterials that exhibit adaptiveness to the biological environment. These materials are specifically designed to stimulate or direct appropriate cell and tissue responses or regulate interactions with microorganisms. The journal covers a wide range of bioactive materials, including those that are engineered or designed in terms of their physical form (e.g. particulate, fiber), topology (e.g. porosity, surface roughness), or dimensions (ranging from macro to nano-scales). Contributions are sought from the following categories of bioactive materials: Bioactive metals and alloys Bioactive inorganics: ceramics, glasses, and carbon-based materials Bioactive polymers and gels Bioactive materials derived from natural sources Bioactive composites These materials find applications in human and veterinary medicine, such as implants, tissue engineering scaffolds, cell/drug/gene carriers, as well as imaging and sensing devices.