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具有免疫调节和胶原蛋白重塑功能的仿酶羟基磷灰石用于糖尿病伤口敷料

Enzyme-Mimetic Hydroxyapatite for Diabetic Wound Dressing with Immunomodulation and Collagen Remodeling Functions.

作者信息

Gao Jiaze, Wu Xiaoyang, Hu Yucai, Wu Kai, Zhou Ting, Wei Dan, Wu Chengheng, Ding Jie, Luo Fang, Sun Jing, Fan Hongsong

机构信息

National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu, Sichuan 610065, China.

Institute of Regulatory Science for Medical Devices, Sichuan University, Chengdu 610065, PR China.

出版信息

ACS Appl Mater Interfaces. 2025 Jun 18;17(24):35116-35127. doi: 10.1021/acsami.5c04696. Epub 2025 Jun 4.

Abstract

Wound dressing is expected to provide protection and a regenerative environment for healing. For diabetic chronic wounds, the characteristic persistent oxidative stress and impaired collagen remodeling present additional challenges. Hydroxyapatite (HAp) with inherent biocompatibility is newly found to have a collagen-stimulating capacity for matrix remodeling. On the other hand, nanoenzyme-like carbon dots (CDs) are feasible for anti-inflammatory and antioxidative stress applications. Inspired by the shared high-temperature synthesis conditions of HAp and CDs, we developed a one-step hydrothermal method to fabricate iron-doped CDs-functionalized HAp (CDs-HAp) to integrate the collagen-stimulating bioactivity of HAp and the multienzyme activity of Fe-CDs. By embedding the CDs-HAp into a biomimetic hydrogel film of dual-cross-linked silk fibroin (DSF), we created a flexible and adhesive wound dressing (CDs-HAp@DSF) with robust ROS scavenging and immunomodulatory functions. We demonstrated that CDs-HAp@DSF can facilitate fibroblast proliferation and collagen synthesis while mitigating oxidative damage and promoting macrophage polarization toward the anti-inflammatory M2 phenotype. , it accelerates diabetic wound healing by synergistically enhancing collagen deposition, suppressing pathological inflammation, and reshaping the regenerative immune microenvironment. This design leverages matrix remodeling and enzymatic ROS elimination to concurrently target oxidative stress, inflammation, and ECM dysregulation, offering a potential therapeutic strategy for chronic diabetic wound healing.

摘要

伤口敷料有望为伤口愈合提供保护和再生环境。对于糖尿病慢性伤口,其特有的持续氧化应激和受损的胶原蛋白重塑带来了额外的挑战。新发现具有固有生物相容性的羟基磷灰石(HAp)具有刺激胶原蛋白进行基质重塑的能力。另一方面,类纳米酶碳点(CDs)可用于抗炎和抗氧化应激应用。受HAp和CDs共有的高温合成条件启发,我们开发了一种一步水热法来制备铁掺杂CDs功能化的HAp(CDs-HAp),以整合HAp的胶原蛋白刺激生物活性和Fe-CDs的多酶活性。通过将CDs-HAp嵌入双交联丝素蛋白(DSF)的仿生水凝胶膜中,我们创建了一种具有强大活性氧清除和免疫调节功能的柔性粘性伤口敷料(CDs-HAp@DSF)。我们证明,CDs-HAp@DSF可以促进成纤维细胞增殖和胶原蛋白合成,同时减轻氧化损伤并促进巨噬细胞向抗炎M2表型极化。此外,它通过协同增强胶原蛋白沉积、抑制病理性炎症和重塑再生免疫微环境来加速糖尿病伤口愈合。这种设计利用基质重塑和酶促活性氧清除来同时针对氧化应激、炎症和细胞外基质失调,为慢性糖尿病伤口愈合提供了一种潜在的治疗策略。

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