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基于硫酸化木糖鼠李糖醛酸的富含鼠李糖的水凝胶的开发及其在伤口愈合中的应用。

Development of rhamnose-rich hydrogels based on sulfated xylorhamno-uronic acid toward wound healing applications.

机构信息

ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, Innovation Campus, University of Wollongong, NSW 2522, Australia.

Venus Shell Systems Pty Ltd, Mundamia, NSW 2540, Australia and School of Medicine, Science, Medicine & Health, University of Wollongong, Wollongong, NSW 2500, Australia.

出版信息

Biomater Sci. 2019 Aug 1;7(8):3497-3509. doi: 10.1039/c9bm00480g. Epub 2019 Jul 10.

DOI:10.1039/c9bm00480g
PMID:31290861
Abstract

An array of biological properties is demonstrated in the category of extracts broadly known as ulvans, including antibacterial, anti-inflammatory and anti-coagulant activities. However, the development of this category in biomedical applications is limited due to high structural variability across species and a lack of consistent and scalable sources. In addition, the modification and formulation of these molecules is still in its infancy with regard to progressing to product development. Here, a sulfated and rhamnose-rich, xylorhamno-uronic acid (XRU) extract from the cell wall of a controlled source of cultivated Australian ulvacean macroalgae resembles mammalian connective glycosaminoglycans. It is therefore a strong candidate for applications in wound healing and tissue regeneration. This study targets the development of polysaccharide modification for fabrication of 3D scaffolds for skin cell (fibroblast) culture. The XRU extract is methacrylated and UV-crosslinked to produce hydrogels with tuneable mechanical properties. The hydrogels demonstrate high cell viability and support cell proliferation over 14 days, which are far more functional than comparable alginate gels. Importantly, an XRU-based bioink is developed for extrusion printing 3D constructs both with and without cell encapsulation. These results highlight the close to product potential of this rhamnose-rich XRU extract as a promising biomaterial toward wound healing. Future studies should be focused on in-depth in vitro characterizations to examine the role of the material in dermal extracellular matrix (ECM) secretion of 3D printed structures, and in vivo characterizations to assess its capacity in supporting wound healing.

摘要

一系列生物特性在被广泛称为岩藻聚糖的提取物类别中得到了证明,包括抗菌、抗炎和抗凝血活性。然而,由于物种间结构变异性高以及缺乏一致和可扩展的来源,该类别的生物医学应用发展受到限制。此外,这些分子的修饰和配方在向产品开发推进方面仍处于起步阶段。在这里,一种来自澳大利亚受控培养的大型绿藻细胞壁的硫酸化和富含鼠李糖的木糖-鼠李糖醛酸(XRU)提取物类似于哺乳动物结缔组织糖胺聚糖。因此,它是应用于伤口愈合和组织再生的强有力候选者。本研究旨在开发多糖修饰,用于制造用于皮肤细胞(成纤维细胞)培养的 3D 支架。XRU 提取物被甲基丙烯酰化并通过 UV 交联,以产生具有可调机械性能的水凝胶。水凝胶表现出高细胞活力,并支持细胞增殖超过 14 天,其功能远远超过可比的海藻酸盐凝胶。重要的是,开发了基于 XRU 的生物墨水,用于挤出打印具有和不具有细胞封装的 3D 结构。这些结果突出了富含鼠李糖的 XRU 提取物作为一种有前途的生物材料在伤口愈合方面的接近产品潜力。未来的研究应集中在深入的体外特性分析上,以研究该材料在 3D 打印结构的真皮细胞外基质(ECM)分泌中的作用,以及体内特性分析,以评估其在支持伤口愈合方面的能力。

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