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明胶/透明质酸/硫酸软骨素/积雪草酸基生物聚合支架的制备及评价及其在治疗二度烧伤创面中的应用- Wistar 大鼠模型研究。

Fabrication and evaluation of gelatin/hyaluronic acid/chondroitin sulfate/asiatic acid based biopolymeric scaffold for the treatment of second-degree burn wounds - Wistar rat model study.

机构信息

Centre for Biomedical Engineering, Indian Institute of Technology Delhi, New Delhi, India. Biomedical Engineering Unit, All India Institute of Medical Sciences, New Delhi, India.

出版信息

Biomed Mater. 2020 Aug 10;15(5):055016. doi: 10.1088/1748-605X/ab8721.

Abstract

An extracellular matrix (ECM) mimicking architecture was introduced with gelatin glycosaminoglycans like hyaluronic acid and chondroitin sulfate and a triterpenoid using asiatic acid, possessing biodegradable and biocompatible properties that mark the functionality for the treatment of second-degree burn wounds. In the present work, a foam-based scaffold was fabricated and sterilized with gamma radiation at a 2.5 Mrad dose. The scaffolds were further characterized for morphology, swelling, degradation behaviour, release of bioactive components, ATR-FTIR, mechanical, thermal properties and compared with control. In vitro cytocompatibility of the developed scaffold was studied with L929 mouse fibroblast cells and human mesenchymal stem cells based on deoxyribonucleic acid and lactate dehydrogenase assay. Additionally, the developed scaffold was evaluated for its biocompatibility on the Wistar rat to assess any toxicity induced to the animal based on blood biochemistry and histopathology analysis. Finally, we assessed the efficacy of developed foam scaffolds on the second-degree burn wound-induced Wistar rat with a scaffold alone and a scaffold seeded with human bone-marrow-derived mesenchymal stem cells in a wound healing study for 28 d. The wound contraction assay, histopathology, immunohistochemistry analysis and pro-healing marker quantification using hexosamine, hydroxyproline, and pro-inflammatory markers like TNF-α and MMP-2 were carried out and compared with the commercially available wound dressing. The results revealed that foam-based ECM mimic was cytocompatible, biocompatible and biodegradable in 18 ± 3 d in in vivo conditions and the scaffold fostered the process of healing of second-degree burns within 28 d of treatment. The obtained result proved that the scaffold has a potential for clinical settings in second-degree burn wound treatment.

摘要

引入了一种模仿细胞外基质 (ECM) 的架构,其中包含明胶糖胺聚糖(如透明质酸和硫酸软骨素)和一种具有生物可降解和生物相容性特性的三萜酸(齐墩果酸),可用于治疗二度烧伤创面。在本工作中,使用伽马射线在 2.5 Mrad 剂量下对基于泡沫的支架进行了灭菌。进一步对支架的形态、溶胀、降解行为、生物活性成分的释放进行了表征,并与对照进行了比较。采用脱氧核糖核酸和乳酸脱氢酶测定法,对 L929 小鼠成纤维细胞和人骨髓间充质干细胞进行了所开发支架的体外细胞相容性研究。此外,还在 Wistar 大鼠上评估了所开发支架的生物相容性,以根据血液生化和组织病理学分析评估对动物的任何毒性。最后,我们在二度烧伤创面诱导的 Wistar 大鼠上评估了所开发泡沫支架的功效,分别单独使用支架和支架接种人骨髓源性间充质干细胞,在 28 天的伤口愈合研究中进行了评估。进行了创面收缩测定、组织病理学、免疫组织化学分析以及使用己糖胺、羟脯氨酸和 TNF-α和 MMP-2 等促愈合标志物的定量分析,并与市售的伤口敷料进行了比较。结果表明,基于泡沫的 ECM 模拟物在体内条件下的细胞相容性、生物相容性和生物降解性为 18 ± 3 d,支架在 28 天的治疗期内促进了二度烧伤的愈合过程。所得结果证明,该支架在治疗二度烧伤创面方面具有临床应用的潜力。

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