Chu Yun Shin, Wong Pei-Chun, Jang Jason Shian-Ching, Chen Chih-Hwa, Wu Si-Han
Graduate Institute of Biomedical Materials and Tissue Engineering, Taipei Medical University, Taipei 11031, Taiwan.
Department of Orthopedics, Taipei Medical University Hospital, Taipei 11031, Taiwan.
Pharmaceutics. 2022 May 17;14(5):1078. doi: 10.3390/pharmaceutics14051078.
Mg-Zn-Ca bulk metallic glass (BMG) is a promising orthopedic fixation implant because of its biodegradable and biocompatible properties. Structural supporting bone implants with osteoinduction properties for effective bone regeneration have been highly desired in recent years. Osteogenic growth peptide (OGP) can increase the proliferation and differentiation of mesenchymal stem cells and enhance the mineralization of osteoblast cells. However, the short half-life and non-specificity to target areas limit applications of OGP. Mesoporous silica nanoparticles (MSNs) as nanocarriers possess excellent properties, such as easy surface modification, superior targeting efficiency, and high loading capacity of drugs or proteins. Accordingly, we propose a system of combining the OGP-containing MSNs with Mg-Zn-Ca BMG materials to promote bone regeneration. In this work, we conjugated cysteine-containing OGP (cgOGP, 16 a.a.) to interior walls of channels in MSNs and maintained the dispersity of MSNs via PEGylation. An in vitro study showed that metal ions released from Mg-Zn-Ca BMG promoted cell proliferation and migration and elevated alkaline phosphatase (ALP) activity and mineralization. On treating cells with both BMG ion-containing Minimum Essential Medium Eagle-alpha modification (α-MEM) and OGP-conjugated MSNs, enhanced focal adhesion turnover and promoted differentiation were observed. Hematological analyses showed the biocompatible nature of this BMG/nanocomposite system. In addition, in vivo micro-computed tomographic and histological observations revealed that our system stimulated osteogenesis and new bone formation around the implant site.
镁锌钙块状金属玻璃（BMG）因其具有可生物降解和生物相容性，是一种很有前景的骨科固定植入物。近年来，人们一直非常渴望获得具有骨诱导特性以实现有效骨再生的结构性支撑骨植入物。成骨生长肽（OGP）可以增加间充质干细胞的增殖和分化，并增强成骨细胞的矿化作用。然而，OGP的半衰期短以及对靶区域的非特异性限制了其应用。介孔二氧化硅纳米颗粒（MSNs）作为纳米载体具有优异的性能，如易于表面修饰、卓越的靶向效率以及药物或蛋白质的高负载能力。因此，我们提出了一种将含OGP的MSNs与镁锌钙BMG材料相结合的系统，以促进骨再生。在这项工作中，我们将含半胱氨酸的OGP（cgOGP，含16个氨基酸）偶联到MSNs通道的内壁，并通过聚乙二醇化保持MSNs的分散性。一项体外研究表明，从镁锌钙BMG释放的金属离子促进了细胞增殖和迁移，并提高了碱性磷酸酶（ALP）活性和矿化作用。在用含BMG离子的伊格尔氏基础培养基α改良型（α-MEM）和偶联OGP的MSNs处理细胞时，观察到粘着斑周转增强和分化促进。血液学分析显示了这种BMG/纳米复合材料系统的生物相容性。此外，体内微型计算机断层扫描和组织学观察表明，我们的系统刺激了植入部位周围的骨生成和新骨形成。
