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从伤口敷料到组织再生:用于慢性伤口个性化治疗的双层药物贴片

From Wound Dressing to Tissue Regeneration: Bilayer Medicated Patches for Personalized Treatments of Chronic Wounds.

作者信息

Bernardoni Sara, Campodoni Elisabetta, Vicinelli Gaia, Saqawa Mohamed, Bonvicini Francesca, Pulze Laura, Baranzini Nicoló, Costantini Giorgia, Montesi Monica, Gentilomi Giovanna Angela, Grimaldi Annalisa, Sandri Monica

机构信息

Institute of Science Technology and Sustainability for Ceramics (ISSMC), National Research Council (CNR), Via Granarolo 64, Faenza 48018, Italy.

Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Studies of Messina, Messina, ME 98122, Italy.

出版信息

ACS Appl Mater Interfaces. 2025 Jun 18;17(24):35240-35261. doi: 10.1021/acsami.5c06444. Epub 2025 Jun 5.

Abstract

Chronic wounds pose a significant healthcare challenge, impairing the quality of life for millions of affected individuals. This phenomenon escalates due to the aging of the population and rising comorbidities. Traditional wound care methods often prove inadequate in dealing with the complexities of chronic wounds; therefore, biomaterials have emerged as promising solutions. In response to this need, this work focuses on the development of a bilayered hybrid patch for the treatment of chronic wounds, designed with a chemical composition and morphology to exert antimicrobial activity to combat local infection and to provide specific support for cell adhesion and tissue regeneration. In particular, using gelatin and chitosan as the main constituent materials, bioactive membranes were developed and functionalized with bioresorbable hydroxyapatite nanoparticles doped with magnesium ions grown on gelatin molecules to boost regenerative stimuli. Then, they were assembled into a bilayered structure with highly tuned chemical and structural features through different fabrication techniques and biodegradation by cross-linking processes. Lastly, to confer antibacterial properties, the lower layer was medicated in situ with Vancomycin hydrochloride (VNC), selected as a case study antibiotic. The developed patches exhibit excellent physiochemical properties, including exudate absorption and moisture permeability, with both features falling within the recommended range for materials for wound healing applications. In addition, both patches exhibit adequate biodegradation times to support effective cell adhesion and proliferation, as well as drug release kinetics, with almost complete release of VNC after 48 h, necessary to achieve thorough wound disinfection. In vitro biological studies have proved their biocompatibility and on-site, long-lasting antimicrobial potential, while in vivo tests, with medicinal leeches' model, have demonstrated their affinity for live tissue and efficacy in supporting endothelial cell proliferation by stimulating the epidermal tissue healing process.

摘要

慢性伤口给医疗保健带来了重大挑战,影响了数百万患者的生活质量。由于人口老龄化和合并症增多,这一现象愈发严重。传统的伤口护理方法往往不足以应对慢性伤口的复杂性;因此,生物材料已成为有前景的解决方案。针对这一需求,本研究致力于开发一种用于治疗慢性伤口的双层混合贴片,其化学成分和形态设计旨在发挥抗菌活性以对抗局部感染,并为细胞黏附和组织再生提供特定支持。具体而言,以明胶和壳聚糖作为主要构成材料,制备了生物活性膜,并通过在明胶分子上生长掺杂镁离子的可生物吸收羟基磷灰石纳米颗粒对其进行功能化处理,以增强再生刺激。然后,通过不同的制造技术和交联过程中的生物降解作用,将它们组装成具有高度可调化学和结构特征的双层结构。最后,为赋予抗菌性能,下层原位用盐酸万古霉素(VNC)进行药物处理,VNC被选为案例研究抗生素。所开发的贴片具有优异的物理化学性质,包括渗出液吸收和透湿性,这两个特性均在伤口愈合应用材料的推荐范围内。此外,两种贴片都具有足够的生物降解时间,以支持有效的细胞黏附和增殖以及药物释放动力学,48小时后VNC几乎完全释放,这对于实现彻底的伤口消毒是必要的。体外生物学研究证明了它们的生物相容性和现场持久的抗菌潜力,而在水蛭模型的体内试验中,证明了它们对活组织的亲和力以及通过刺激表皮组织愈合过程支持内皮细胞增殖的功效。

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