In vitro and in vivo assessment of a non-animal sourced chitosan scaffold loaded with xeno-free umbilical cord mesenchymal stromal cells cultured under macromolecular crowding conditions

Q3 Biochemistry, Genetics and Molecular Biology
Alessia Di Nubila , Meletios-Nikolaos Doulgkeroglou , Mehmet Gurdal , Stefanie H. Korntner , Dimitrios I. Zeugolis
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Abstract

There is an increasing demand to not only accelerate the development of advanced therapy tissue engineered medicines, but to also eliminate xenogeneic materials from their development cycle. With these in mind, herein we first assessed the influence of carrageenan as macromolecular crowding agent to enhance and accelerate extracellular matrix deposition in xeno-free human umbilical cord mesenchymal stromal cell cultures and we developed and characterised a non-animal sourced chitosan scaffold. Following appropriate in vitro experimentation, a splinted nude mouse wound healing model was used to assess wound closure and scar size of non-treated control, non-animal sourced chitosan scaffold, non-animal sourced chitosan scaffold loaded with xeno-free human umbilical cord mesenchymal stromal cells and non-animal sourced chitosan scaffold loaded with xeno-free human umbilical cord mesenchymal stromal cells cultured under macromolecular crowding conditions groups. Across all three donors, carrageenan supplementation significantly increased collagen deposition at day 5, day 8 and day 11 without affecting cell morphology, viability, DNA concentration and metabolic activity. Through freeze drying, a non-animal sourced chitosan sponge was developed with appropriate structural and mechanical properties for wound healing applications. In vitro biological analysis made apparent that neither the scaffold nor macromolecular crowding negatively impacted xeno-free human umbilical cord mesenchymal stromal cell metabolic activity and proliferation. In vivo biological analysis revealed no significant differences between the groups in wound closure and scar size, raising question about the suitability of the model. In any case, this work sets the foundations for the development of completely xeno-free tissue engineered medicines.

Abstract Image

在大分子拥挤条件下培养的无异种脐带间充质基质细胞负载的非动物来源壳聚糖支架的体外和体内评估
人们不仅要求加快先进治疗组织工程药物的开发,而且还要求在其开发周期中剔除异种材料,这种需求与日俱增。有鉴于此,我们在本文中首先评估了卡拉胶作为大分子排挤剂对增强和加速细胞外基质在无异种人脐带间充质基质细胞培养物中沉积的影响,并开发和鉴定了一种非动物来源壳聚糖支架。在进行适当的体外实验后,我们用夹板裸鼠伤口愈合模型评估了未经处理的对照组、非动物来源壳聚糖支架组、负载无异氧人脐带间充质基质细胞的非动物来源壳聚糖支架组和负载无异氧人脐带间充质基质细胞的非动物来源壳聚糖支架组在大分子拥挤条件下培养的伤口闭合情况和疤痕大小。在所有三种供体中,角叉菜胶补充剂显著增加了第 5 天、第 8 天和第 11 天的胶原沉积,而不会影响细胞形态、存活率、DNA 浓度和代谢活性。通过冷冻干燥,开发出了一种非动物来源的壳聚糖海绵,具有适当的结构和机械性能,可用于伤口愈合。体外生物分析表明,支架和大分子拥挤都不会对无异种人脐带间充质基质细胞的代谢活性和增殖产生负面影响。体内生物学分析表明,各组之间在伤口闭合和疤痕大小方面没有明显差异,这不禁让人怀疑该模型是否合适。无论如何,这项工作为开发完全不含异种组织工程药物奠定了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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