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用于止血和临界尺寸骨再生的多功能载柚皮苷生物玻璃/羧甲基壳聚糖/丝素蛋白多孔支架的研制

Development of a multi-functional naringin-loaded bioglass/carboxymethyl chitosan/silk fibroin porous scaffold for hemostasis and critical size bone regeneration.

作者信息

Wang Zhaozhen, Shi Yiwan, Gao Botao, Dang Zhaohui, Yang Shan, Chung Chia-Hsuan, Yu Xiaolu, Zhou Xinting, Lin Zefeng, Cheang Lek Hang, Tam Man Seng, Wang Huajun, Zheng Xiaofei, Wu Tingting

机构信息

National Engineering Research Center for Healthcare Devices, Guangdong Provincial Key Laboratory of Medical Electronic Instruments and Materials, Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, Guangzhou 510316, China; Department of Sports Medicine, The First Affiliated Hospital, Guangdong Provincial Key Laboratory of Speed Capability, The Guangzhou Key Laboratory of Precision Orthopedics and Regenerative Medicine, Jinan University, 510630 Guangzhou, China; Orthopedic and traumatology department, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.

National Engineering Research Center for Healthcare Devices, Guangdong Provincial Key Laboratory of Medical Electronic Instruments and Materials, Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, Guangzhou 510316, China; Department of Sports Medicine, The First Affiliated Hospital, Guangdong Provincial Key Laboratory of Speed Capability, The Guangzhou Key Laboratory of Precision Orthopedics and Regenerative Medicine, Jinan University, 510630 Guangzhou, China.

出版信息

Int J Biol Macromol. 2025 Feb;290:138888. doi: 10.1016/j.ijbiomac.2024.138888. Epub 2024 Dec 17.

DOI:10.1016/j.ijbiomac.2024.138888
PMID:39701255
Abstract

Persistent bleeding and limited repair capacity greatly threaten patients with bone destruction. Designing inorganic-organic biomimetic scaffolds with quick hemostasis and osteogenesis functions will solve this problem. A novel degradable and naringin (NG) loaded porous scaffold (SCB-N) based on APTES-modified bioactive glass (ABG), carboxymethyl chitosan and silk fibroin is developed. ABG and NG enhance the strength of the scaffolds. The scaffolds can release NG and bioactive ions (Ca and Si), promoting the expression of osteogenesis (OCN, BMP-2), angiogenesis (VEGF), and neurogenesis (TB3, GFAP) genes in bone mesenchymal stem cells (BMSCs) and the related proteins (OCN, BMP-2, VEGF, GFAP). When implanting the scaffolds in rat cranial critical size defects, all scaffolds exhibit good compatibility, and SCB-N2 (with ABG and 1 mg/mL NG) group significantly promotes new bone regeneration and the formation of M2-type macrophages. Transcriptome sequencing results confirmed the osteogenic differentiation of BMSCs stimulated by SCB-N2 scaffolds is mainly regulated through MAPK and Wnt signaling pathways. Moreover, SCB-N2 group demonstrates quick hemostasis in vitro and in vivo due to the high adsorption ability and Ca ions release. The novel bionic scaffolds loaded with ion/traditional Chinese medicine monomer, possess the capabilities of hemostasis, neurovascularization, osteogenesis and immunomodulation, therefore exhibiting potential in bone repair.

摘要

持续性出血和有限的修复能力对骨破坏患者构成了极大威胁。设计具有快速止血和成骨功能的无机-有机仿生支架将解决这一问题。基于APTES修饰的生物活性玻璃(ABG)、羧甲基壳聚糖和丝素蛋白,开发了一种新型的可降解且负载柚皮苷(NG)的多孔支架(SCB-N)。ABG和NG增强了支架的强度。该支架能够释放NG和生物活性离子(钙和硅),促进骨间充质干细胞(BMSCs)中与成骨(OCN、BMP-2)、血管生成(VEGF)和神经生成(TB3、GFAP)相关的基因以及相关蛋白(OCN、BMP-2、VEGF、GFAP)的表达。当将该支架植入大鼠颅骨临界尺寸缺损处时,所有支架均表现出良好的生物相容性,且SCB-N2(含ABG和1mg/mL NG)组显著促进了新骨再生和M2型巨噬细胞的形成。转录组测序结果证实,SCB-N2支架刺激的BMSCs的成骨分化主要通过MAPK和Wnt信号通路进行调节。此外,由于具有高吸附能力和钙离子释放,SCB-N2组在体外和体内均表现出快速止血的效果。这种负载离子/中药单体的新型仿生支架具有止血、神经血管化、成骨和免疫调节能力,因此在骨修复方面具有潜力。

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