Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea.
Department of Nanobiomedical Science and BK21 NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea.
Adv Healthc Mater. 2024 Aug;13(20):e2400154. doi: 10.1002/adhm.202400154. Epub 2024 Apr 29.
Articular cartilage defects are a global challenge, causing substantial disability. Repairing large defects is problematic, often exceeding cartilage's self-healing capacity and damaging bone structures. To tackle this problem, a scaffold-mediated therapeutic ion delivery system is developed. These scaffolds are constructed from poly(ε-caprolactone) and strontium (Sr)-doped bioactive nanoglasses (SrBGn), creating a unique hierarchical structure featuring macropores from 3D printing, micropores, and nanotopologies due to SrBGn integration. The SrBGn-embedded scaffolds (SrBGn-µCh) release Sr, silicon (Si), and calcium (Ca) ions, which improve chondrocyte activation, adhesion, proliferation, and maturation-related gene expression. This multiple ion delivery significantly affects metabolic activity and maturation of chondrocytes. Importantly, Sr ions may play a role in chondrocyte regulation through the Notch signaling pathway. Notably, the scaffold's structure and topological cues expedite the recruitment, adhesion, spreading, and proliferation of chondrocytes and bone marrow-derived mesenchymal stem cells. Si and Ca ions accelerate osteogenic differentiation and blood vessel formation, while Sr ions enhance the polarization of M2 macrophages. The findings show that SrBGn-µCh scaffolds accelerate osteochondral defect repair by delivering multiple ions and providing structural/topological cues, ultimately supporting host cell functions and defect healing. This scaffold holds great promise for osteochondral repair applications.
关节软骨缺损是一个全球性的挑战,会导致严重的残疾。修复大的缺损是有问题的,因为它通常超过了软骨的自我修复能力,并会损害骨结构。为了解决这个问题,开发了一种支架介导的治疗离子输送系统。这些支架由聚己内酯和锶(Sr)掺杂的生物活性纳米玻璃(SrBGn)构建而成,由于 SrBGn 的掺入,形成了一种独特的具有大孔(来自 3D 打印)、微孔和纳米拓扑结构的分层结构。SrBGn 嵌入的支架(SrBGn-µCh)释放 Sr、硅(Si)和钙(Ca)离子,这些离子可提高软骨细胞的激活、黏附、增殖和成熟相关基因的表达。这种多种离子的输送显著影响了软骨细胞的代谢活性和成熟。重要的是,Sr 离子可能通过 Notch 信号通路在软骨细胞调节中发挥作用。值得注意的是,支架的结构和拓扑线索促进了软骨细胞和骨髓间充质干细胞的募集、黏附、扩展和增殖。Si 和 Ca 离子加速成骨分化和血管形成,而 Sr 离子增强 M2 巨噬细胞的极化。研究结果表明,SrBGn-µCh 支架通过输送多种离子和提供结构/拓扑线索,加速了骨软骨缺损的修复,最终支持宿主细胞的功能和缺损的愈合。该支架在骨软骨修复应用中具有很大的应用前景。