Sutthavas Pichaporn, Schumacher Matthias, Zheng Kai, Habibović Pamela, Boccaccini Aldo Roberto, van Rijt Sabine
Department of Instructive Biomaterials Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, Nanjing 210029, China.
Nanomaterials (Basel). 2022 Aug 24;12(17):2918. doi: 10.3390/nano12172918.
Nanoparticles such as mesoporous bioactive glasses (MBGs) and mesoporous silica nanoparticles (MSN) are promising for use in bone regeneration applications due to their inherent bioactivity. Doping silica nanoparticles with bioinorganic ions could further enhance their biological performance. For example, zinc (Zn) is often used as an additive because it plays an important role in bone formation and development. Local delivery and dose control are important aspects of its therapeutic application. In this work, we investigated how Zn incorporation in MSN and MBG nanoparticles impacts their ability to promote human mesenchymal stem cell (hMSC) osteogenesis and mineralization in vitro. Zn ions were incorporated in three different ways; within the matrix, on the surface or in the mesopores. The nanoparticles were further coated with a calcium phosphate (CaP) layer to allow pH-responsive delivery of the ions. We demonstrate that the Zn incorporation amount and ion release profile affect the nanoparticle's ability to stimulate osteogenesis in hMSCs. Specifically, we show that the nanoparticles that contain rapid Zn release profiles and a degradable silica matrix were most effective in inducing hMSC differentiation. Moreover, cells cultured in the presence of nanoparticle-containing media resulted in the highest induction of alkaline phosphate (ALP) activity, followed by culturing hMSC on nanoparticles immobilized on the surface as films. Exposure to nanoparticle-conditioned media did not increase ALP activity in hMSCs. In summary, Zn incorporation mode and nanoparticle application play an important role in determining the bioactivity of ion-doped silica nanoparticles.
诸如介孔生物活性玻璃（MBG）和介孔二氧化硅纳米颗粒（MSN）之类的纳米颗粒因其固有的生物活性而有望用于骨再生应用。用生物无机离子掺杂二氧化硅纳米颗粒可以进一步提高其生物学性能。例如，锌（Zn）经常被用作添加剂，因为它在骨骼形成和发育中起重要作用。局部递送和剂量控制是其治疗应用的重要方面。在这项工作中，我们研究了在MSN和MBG纳米颗粒中掺入锌如何影响它们在体外促进人间充质干细胞（hMSC）成骨和矿化的能力。锌离子以三种不同方式掺入；在基质内、表面或介孔中。纳米颗粒进一步涂覆有磷酸钙（CaP）层，以实现离子的pH响应性递送。我们证明锌的掺入量和离子释放曲线会影响纳米颗粒刺激hMSC成骨的能力。具体而言，我们表明具有快速锌释放曲线和可降解二氧化硅基质的纳米颗粒在诱导hMSC分化方面最有效。此外，在含有纳米颗粒的培养基中培养的细胞导致碱性磷酸酶（ALP）活性的诱导最高，其次是将hMSC培养在固定在表面的纳米颗粒薄膜上。暴露于纳米颗粒条件培养基不会增加hMSC中的ALP活性。总之，锌掺入模式和纳米颗粒应用在确定离子掺杂二氧化硅纳米颗粒的生物活性方面起着重要作用。
