Harnessing extracellular vesicles-mediated signaling for enhanced bone regeneration: novel insights into scaffold design.

Hemalatha Kanniyappan, Varun Gnanasekar, Vincent Parise, Koushik Debnath, Yani Sun, Shriya Thakur, Gitika Thakur, Govindaraj Perumal, Raj Kumar, Rong Wang, Aftab Merchant, Ravindran Sriram, Mathew T Mathew
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Abstract

The increasing prevalence of bone replacements and complications associated with bone replacement procedures underscores the need for innovative tissue restoration approaches. Existing synthetic grafts cannot fully replicate bone vascularization and mechanical characteristics. This study introduces a novel strategy utilizing pectin, chitosan, and polyvinyl alcohol to create interpenetrating polymeric network (IPN) scaffolds incorporated with extracellular vesicles (EVs) isolated from human mesenchymal stem cells (hMSCs). We assess the osteointegration and osteoconduction abilities of these modelsin vitrousing hMSCs and MG-63 osteosarcoma cells. Additionally, we confirm exosome properties through Transmission Electron Microscopy (TEM), immunoblotting, and Dynamic Light Scattering (DLS).In vivo, chick allantoic membrane assay investigates vascularization characteristics. The study did not includein vivoanimal experiments. Our results demonstrate that the IPN scaffold is highly porous and interconnected, potentially suitable for bone implants. EVs, approximately 100 nm in size, enhance cell survival, proliferation, alkaline phosphatase activity, and the expression of osteogenic genes. EVs-mediated IPN scaffolds demonstrate promise as precise drug carriers, enabling customized treatments for bone-related conditions and regeneration efforts. Therefore, the EVs-mediated IPN scaffolds demonstrate promise as precise carriers for the transport of drugs, allowing for customized treatments for conditions connected to bone and efforts in regeneration.

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利用细胞外囊泡介导的信号传导促进骨再生:支架设计的新见解。
骨替代手术越来越普遍,而与骨替代手术相关的并发症也越来越多,这凸显了对创新组织修复方法的需求。现有的合成移植物无法完全复制骨的血管化和机械特性。本研究介绍了一种利用果胶、壳聚糖和 PVA 创建互穿聚合物网络(IPN)支架的新策略,其中包含从人间充质干细胞中分离出的细胞外囊泡(EVs)。我们利用人间充质干细胞和 MG-63 骨肉瘤细胞在体外评估了这些模型的骨整合和骨传导能力。此外,我们还通过 TEM、免疫印迹和 DLS 确认了外泌体的特性。在体内,CAM 试验研究了血管化特征。该研究不包括体内动物实验。我们的研究结果表明,IPN 支架具有高度多孔性和互连性,可能适用于骨植入物。大小约为 100 nm 的 EVs 可提高细胞存活率、增殖率、ALP 活性和成骨基因的表达。由 EVs 介导的 IPN 支架有望成为精确的药物载体,为骨骼相关疾病和再生工作提供定制治疗。因此,EVs 介导的 IPN 支架有望成为精确的药物运输载体,从而为骨骼相关疾病和再生工作提供定制化治疗。
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