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含铜介孔生物活性玻璃与纳米原纤化纤维素的生物复合材料:在慢性伤口愈合应用中的生物相容性及促血管生成作用

Biocomposites of copper-containing mesoporous bioactive glass and nanofibrillated cellulose: Biocompatibility and angiogenic promotion in chronic wound healing application.

作者信息

Wang Xiaoju, Cheng Fang, Liu Jun, Smått Jan-Henrik, Gepperth David, Lastusaari Mika, Xu Chunlin, Hupa Leena

机构信息

Johan Gadolin Process Chemistry Centre, Åbo Akademi University, FI-20500 Åbo/Turku, Finland.

Cell Biology, Biosciences, Faculty of Science and Engineering, Åbo Akademi University & Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland.

出版信息

Acta Biomater. 2016 Dec;46:286-298. doi: 10.1016/j.actbio.2016.09.021. Epub 2016 Sep 17.

Abstract

UNLABELLED

Biocomposites of copper-containing mesoporous bioactive glass (Cu-MBG) and nanofibrillated cellulose (NFC) were designated as potential dressing material for chronic wound healing. The phase composition and mesoporous micro-structure of the synthesized Cu-MBGs were elaborately characterized by combining several techniques, including TEM, SEM, XRD, SXAS and N physisorption. High bioactivity of the Cu-MBG was confirmed in stimulated body fluids in vitro. A controlled dissolution of Cu from the glass suggests Cu-MBG a suitable source for Cu release in wound healing dressings. Depending on the content of Cu-MBG in the composite formulation, the composites were fabricated as membranes and aerogels. In biocompatibility assessment of the composites, a dose-dependent cytotoxicity of Cu on 3T3 fibroblasts was found. Importantly, a critical biological level of Cu below 10mg/L was suggested for the survival and growth of 3T3 fibroblasts. The Cu released from the composite aerogel of NFC and Cu-MBG showed a profound angiogenic effect in the 3D spheroid culture system of human umbilical vein endothelial cells. Moreover, the angiogenic gene expression of 3T3 fibroblast was upregulated in the real-time quantitative PCR analysis, which also confirms that the incorporation of Cu-MBG into NFC matrix enhances the proangiogenic potential of the biocomposites. In addition, composites of NFC and Cu-MBG also showed an inhibiting effect on the growth of E. coli.

STATEMENT OF SIGNIFICANCE

To address an urgent need in clinics on developing a new generation of therapeutic dressings with advanced functionalities, this study has exploited the utilization of Cu-containing mesoporous bioactive glass in the nanocellulose matrix to release Cu as therapeutic ions for its angiogenic effect on promoting wound healing. This manuscript reports research work on biomaterial design, fabrication development, material characterizations and bioassessments in 2D cellular studies. To utilize nanocellulose derived from the wood resource in biomedical applications is of great significance, due to its vast availability and bioeconomy competence. The use of Cu-containing bioactive glass in tissue engineering scaffolds, including wound healing, is an intriguing research topic, which has been recently discussed in the field of biomaterials. I think that our manuscript title with 'Biocomposites of copper-containing mesoporous bioactive glass and nanofibrillated cellulose: biocompatibility and angiogenic promotion in chronic wound healing application' will make its own contribution on understanding the complex effects of Cu on wound-healing-relevant events with acceptable novelty for Acta Biomaterialia.

摘要

未标记

含铜介孔生物活性玻璃(Cu-MBG)与纳米原纤化纤维素(NFC)的生物复合材料被指定为慢性伤口愈合的潜在敷料材料。通过结合多种技术,包括透射电子显微镜(TEM)、扫描电子显微镜(SEM)、X射线衍射(XRD)、软X射线吸收光谱(SXAS)和N物理吸附,对合成的Cu-MBG的相组成和介孔微观结构进行了详细表征。在体外模拟体液中证实了Cu-MBG具有高生物活性。玻璃中Cu的可控溶解表明Cu-MBG是伤口愈合敷料中Cu释放的合适来源。根据复合配方中Cu-MBG的含量,将复合材料制成膜和气凝胶。在复合材料的生物相容性评估中,发现Cu对3T3成纤维细胞具有剂量依赖性细胞毒性。重要的是,建议3T3成纤维细胞存活和生长的Cu临界生物学水平低于10mg/L。从NFC和Cu-MBG的复合气凝胶中释放的Cu在人脐静脉内皮细胞的3D球体培养系统中显示出显著的血管生成作用。此外,实时定量PCR分析中3T3成纤维细胞的血管生成基因表达上调,这也证实了将Cu-MBG掺入NFC基质中可增强生物复合材料的促血管生成潜力。此外,NFC和Cu-MBG的复合材料对大肠杆菌的生长也表现出抑制作用。

意义声明

为满足临床对开发具有先进功能的新一代治疗性敷料的迫切需求,本研究利用含铜介孔生物活性玻璃在纳米纤维素基质中的应用,释放Cu作为治疗离子,以发挥其促进伤口愈合的血管生成作用。本手稿报告了二维细胞研究中生物材料设计、制造开发、材料表征和生物评估的研究工作。由于其丰富的可用性和生物经济竞争力,将源自木材资源的纳米纤维素用于生物医学应用具有重要意义。在包括伤口愈合在内的组织工程支架中使用含铜生物活性玻璃是一个有趣的研究课题,最近在生物材料领域进行了讨论。我认为我们的手稿标题“含铜介孔生物活性玻璃与纳米原纤化纤维素的生物复合材料:在慢性伤口愈合应用中的生物相容性和血管生成促进作用”将为理解Cu对伤口愈合相关事件的复杂影响做出贡献,对《生物材料学报》具有可接受的新颖性。

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