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钛和姜黄素共嵌入脱细胞骨细胞外基质水凝胶的双重协同效应:在脂肪来源间充质干细胞成骨分化中的潜在应用。

A dual synergistic effect of titanium and curcumin co-embedded on extracellular matrix hydrogels of decellularized bone: Potential application in osteoblastic differentiation of adipose-derived mesenchymal stem cells.

作者信息

Amirazad Halimeh, Baradar Khoshfetrat Ali, Zarghami Nosratollah

机构信息

Department of Medical Biotechnology, Faculty of Advanced Medical Science, Tabriz University of Medical Sciences, Tabriz, Iran.

Chemical Engineering Faculty, Sahand University of Technology, Tabriz, Iran.

出版信息

J Biomater Sci Polym Ed. 2023 Feb;34(3):372-397. doi: 10.1080/09205063.2022.2123216. Epub 2022 Oct 2.

DOI:10.1080/09205063.2022.2123216
PMID:36071650
Abstract

This research aims to design and fabricate a novel hydrogel-based composite as a functional biomimetic and biocompatible scaffold for amended osteoblastic differentiation of adipose-derived mesenchymal stem cells (ADMSCs). The extracellular matrix (ECM) hydrogel is an ideal scaffold in tissue engineering in terms of its structure mimics natural tissue. In this study, the fresh bovine femur was demineralized and decellularized; next, ECM hydrogel was obtained by digesting these matrices. Then, TiO and curcumin-loaded hydrogel (Hy/Ti/Cur) was fabricated besides TiO-loaded hydrogel (Hy/Ti) and curcumin-loaded hydrogel (Hy/Cur). Comparing the scanning electron microscopy (SEM) images of the pure network hydrogel and the rough morphology of Hy/Ti/Cur revealed that curcumin and titanium dioxide were successfully loaded into the hydrogel. In addition, FTIR spectroscopy and X-ray diffraction (XRD) validated these findings. The findings of the hydrogels' swelling test indicated the favourable impact of curcumin and titanium dioxide in hydrogels, which enhances water absorption capacity. Our results showed that the hydrogels were cytocompatible, and the cell viability on the hydrogels was elevated compared to the control. The synergistic effect of TiO and Cur co-embedded on ECM hydrogel (Hy/Ti/Cur) stimulates bone differentiation markers, such as Runt-related transcription factor 2 (RUNX-2) and osteocalcin (OCN) in ADMSCs cultured in normal and osteogenic medium. Moreover, Alkaline Phosphatase (ALP) activity and calcium deposition of ADMSCs cultured on engineered hydrogels were increased. These experiments showed that newly fabricated hydrogel has the potential to induce osteogenesis, which is recommended as an attractive scaffold in bone tissue engineering.

摘要

本研究旨在设计并制备一种新型水凝胶基复合材料,作为一种功能性仿生且生物相容的支架,用于改善脂肪来源间充质干细胞(ADMSCs)的成骨分化。细胞外基质(ECM)水凝胶在组织工程中是一种理想的支架,因其结构模拟天然组织。在本研究中,将新鲜牛股骨进行脱矿质和脱细胞处理;接下来,通过消化这些基质获得ECM水凝胶。然后,除了制备负载二氧化钛的水凝胶(Hy/Ti)和负载姜黄素的水凝胶(Hy/Cur)外,还制备了负载二氧化钛和姜黄素的水凝胶(Hy/Ti/Cur)。比较纯网络水凝胶的扫描电子显微镜(SEM)图像与Hy/Ti/Cur的粗糙形态,结果表明姜黄素和二氧化钛成功负载到了水凝胶中。此外,傅里叶变换红外光谱(FTIR)和X射线衍射(XRD)验证了这些结果。水凝胶溶胀试验的结果表明,姜黄素和二氧化钛对水凝胶有良好影响,可提高其吸水能力。我们的结果表明,这些水凝胶具有细胞相容性,与对照组相比,水凝胶上的细胞活力有所提高。共嵌入到ECM水凝胶(Hy/Ti/Cur)中的二氧化钛和姜黄素的协同作用,刺激了在正常和成骨培养基中培养的ADMSCs中的骨分化标志物,如Runx相关转录因子2(RUNX - 2)和骨钙素(OCN)。此外,在工程水凝胶上培养的ADMSCs的碱性磷酸酶(ALP)活性和钙沉积增加。这些实验表明,新制备的水凝胶具有诱导成骨的潜力,推荐作为骨组织工程中有吸引力的支架。

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