Synergistic effects of astragalus on 3D-printed calcium silicate/poly-ε-caprolactone scaffolds to regulate inflammation/osteogenesis for bone regeneration

IF 5.2 Q2 MATERIALS SCIENCE, MULTIDISCIPLINARY
Jian-Jr Lee, Yen-Hong Lin, Ting-You Kuo, Alvin Kai-Xing Lee, Cheng-Yu Chen and Ming-You Shie
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Abstract

Bone defects represent a significant clinical challenge, traditionally addressed primarily through scaffold-based repair strategies. However, recent studies have revealed that relying solely on scaffolds may not fully overcome the bottlenecks in bone defect repair. Mounting evidence suggests that modulating the inflammatory response plays a crucial role in the bone healing process. While moderate inflammation can promote bone tissue regeneration, excessive or prolonged inflammatory responses may impede the repair process. Our previously developed calcium silicate (CS) scaffold, known to stimulate osteoblast proliferation and accelerate bone tissue formation, was enhanced with magnesium–strontium to boost cellular biological activity and foster bone formation and angiogenesis. In this study, the effects of 3D-printed CS scaffolds reinforced with astragalus (Ast) on inflammation regulation and osteogenic gene expression were examined. X-ray diffraction and Fourier transform infrared spectroscopy confirmed that the Ast phase structure and chemical functional groups were added to the materials. The findings revealed that integrating Ast improves scaffold biocompatibility, bioactivity, and bone and vascular tissue formation efficacy, enhances mechanical strength, and decelerates biodegradation. The 5% Ast-containing CS scaffold exhibited superior capabilities in promoting cell proliferation and differentiation, indicative of effective bone regeneration. Moreover, analysis of hMSC-seeded AstCS scaffold supernatants revealed significantly reduced levels of pro-inflammatory cytokines IL-1β and IL-6, coupled with elevated expression of the anti-inflammatory factor IL-1RA. These results suggest that Astragalus incorporation effectively modulates inflammatory signaling in the scaffold microenvironment. Transcriptome RNA sequencing revealed that this scaffold modulated multiple signaling pathways crucial for bone regeneration, such as WNT, AKT, and PI3K, and significantly influenced genes associated with cellular bone regeneration, angiogenesis, and immune responses. These results highlight the potential of combining Ast with CS in 3D-printed scaffolds for bone tissue engineering, offering new strategies for employing natural pharmaceutical ingredients as bioactivity enhancers and providing a substantial foundation for designing future bone regeneration materials with immune-modulating capabilities.

Abstract Image

黄芪对三维打印硅酸钙/聚ε-己内酯支架的协同作用,可调节炎症/骨生成,促进骨再生
骨缺损是一项重大的临床挑战,传统上主要通过基于支架的修复策略来解决。然而,最近的研究表明,仅仅依靠支架可能无法完全克服骨缺损修复的瓶颈。越来越多的证据表明,调节炎症反应在骨愈合过程中起着至关重要的作用。虽然适度的炎症可以促进骨组织再生,但过度或长时间的炎症反应可能会阻碍修复过程。我们之前开发的硅酸钙(CS)支架具有刺激成骨细胞增殖和加速骨组织形成的作用,通过添加镁锶来增强细胞的生物活性,促进骨形成和血管生成。本研究考察了用黄芪(Ast)增强的三维打印 CS 支架对炎症调节和成骨基因表达的影响。X 射线衍射和傅立叶变换红外光谱证实,材料中添加了 Ast 相结构和化学官能团。研究结果表明,添加 Ast 能改善支架的生物相容性、生物活性、骨和血管组织形成效果,提高机械强度,并减缓生物降解。含5% Ast的CS支架在促进细胞增殖和分化方面表现出卓越的能力,这表明它能有效促进骨再生。此外,对播种了 AstCS 支架的 hMSC 上清液的分析表明,促炎细胞因子 IL-1β 和 IL-6 的水平显著降低,而抗炎因子 IL-1RA 的表达则有所升高。这些结果表明,黄芪的加入能有效调节支架微环境中的炎症信号转导。转录组 RNA 测序显示,这种支架调节了对骨再生至关重要的多种信号通路,如 WNT、AKT 和 PI3K,并显著影响了与细胞骨再生、血管生成和免疫反应相关的基因。这些结果凸显了将 Ast 与 CS 结合用于骨组织工程三维打印支架的潜力,为采用天然药物成分作为生物活性增强剂提供了新的策略,并为设计具有免疫调节功能的未来骨再生材料奠定了坚实的基础。
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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来源期刊
Materials Advances
Materials Advances MATERIALS SCIENCE, MULTIDISCIPLINARY-
CiteScore
7.60
自引率
2.00%
发文量
665
审稿时长
5 weeks
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