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活性氧清除水凝胶作为保护性载体,用于调节干细胞活性并促进骨质疏松症中3D打印多孔钛假体的骨整合。

ROS-scavenging hydrogel as protective carrier to regulate stem cells activity and promote osteointegration of 3D printed porous titanium prosthesis in osteoporosis.

作者信息

Ding Wenbin, Zhou Qirong, Lu Yifeng, Wei Qiang, Tang Hao, Zhang Donghua, Liu Zhixiao, Wang Guangchao, Wu Dajiang

机构信息

Department of Orthopaedics, Changhai Hospital, Second Military Medical University, Shanghai, China.

Department of Histology and Embryology, College of Basic Medicine, Shanghai, China.

出版信息

Front Bioeng Biotechnol. 2023 Jan 17;11:1103611. doi: 10.3389/fbioe.2023.1103611. eCollection 2023.

Abstract

Stem cell-based therapy has drawn attention as an alternative option for promoting prosthetic osteointegration in osteoporosis by virtue of its unique characteristics. However, estrogen deficiency is the main mechanism of postmenopausal osteoporosis. Estrogen, as an effective antioxidant, deficienncy also results in the accumulation of reactive oxygen species (ROS) in the body, affecting the osteogenic differentiation of stem cells and the bone formation i osteoporosis. In this study, we prepared a ROS-scavenging hydrogel by crosslinking of epigallocatechin-3-gallate (EGCG), 3-acrylamido phenylboronic acid (APBA) and acrylamide. The engineered hydrogel can scavenge ROS efficiently, enabling it to be a cell carrier of bone marrow-derived mesenchymal stem cells (BMSCs) to protect delivered cells from ROS-mediated death and osteogenesis inhibition, favorably enhancing the tissue repair potential of stem cells. Further investigations seriously demonstrated that this ROS-scavenging hydrogel encapsulated with BMSCs can prominently promote osteointegration of 3D printed microporous titanium alloy prosthesis in osteoporosis, including scavenging accumulated ROS, inducing macrophages to polarize toward M2 phenotype, suppressing inflammatory cytokines expression, and improving osteogenesis related markers (e.g., ALP, Runx-2, COL-1, BSP, OCN, and OPN). This work provides a novel strategy for conquering the challenge of transplanted stem cells cannot fully function in the impaired microenvironment, and enhancing prosthetic osteointegration in osteoporosis.

摘要

基于干细胞的疗法凭借其独特特性,作为促进骨质疏松症中假体骨整合的替代选择而备受关注。然而,雌激素缺乏是绝经后骨质疏松症的主要机制。雌激素作为一种有效的抗氧化剂,其缺乏还会导致体内活性氧(ROS)的积累,影响干细胞的成骨分化以及骨质疏松症中的骨形成。在本研究中,我们通过表没食子儿茶素 -3- 没食子酸酯(EGCG)、3- 丙烯酰胺基苯硼酸(APBA)和丙烯酰胺交联制备了一种ROS清除水凝胶。这种工程化水凝胶能够有效清除ROS,使其成为骨髓间充质干细胞(BMSCs)的细胞载体,保护递送的细胞免受ROS介导的死亡和成骨抑制,从而有利地增强干细胞的组织修复潜力。进一步的研究确切表明,这种包裹有BMSCs的ROS清除水凝胶能够显著促进骨质疏松症中3D打印微孔钛合金假体的骨整合,包括清除积累的ROS、诱导巨噬细胞向M2表型极化、抑制炎性细胞因子表达以及改善成骨相关标志物(如碱性磷酸酶、Runx-2、I型胶原、骨唾液蛋白、骨钙素和骨桥蛋白)。这项工作为克服移植干细胞在受损微环境中不能充分发挥功能的挑战以及增强骨质疏松症中假体骨整合提供了一种新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d4b/9887181/af0d6e433699/FBIOE_fbioe-2023-1103611_wc_sch1.jpg

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