Zn-Loaded and Calcium Phosphate-Coated Degradable Silica Nanoparticles Can Effectively Promote Osteogenesis in Human Mesenchymal Stem Cells

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

Laser-based ion doping is a suitable alternative to dope biologically active ions into colloidal bioglass nanoparticles

Bioactive glass nanoparticles (nBGs) have demonstrated promising properties for bone regeneration due to their bone-binding ability. Incorporating multiple ions into nBGs can improve their bioactivity and provide them with additional functionalities aiding bone repair. However, incorporating multiple ions into nBGs combining different functionalities is still challenging as the additional ions often interfere with the nanoparticle properties. To overcome these challenges, here we report the use of pulsed laser doping and co-doping techniques as an alternative method for ion incorporation into colloidal nBGs. We demonstrate the simultaneous laser-induced incorporation of iron (Fe), strontium (Sr), and/or copper (Cu) ions into nBGs from simple salt solutions without altering the particles' morphology. Furthermore, laser-doped nBGs were biocompatible and could significantly increase alkaline phosphatase (ALP) production in human mesenchymal stromal cells (hMSC). Moreover, laser-co-doped nBGs containing Fe and Sr ions significantly increased vessel formation by human umbilical vein endothelial cells (HUVEC). Therefore, pulsed laser doping in liquids was shown to be a versatile technique to incorporate multiple ions into nBGs and allow systematic studies on cooperative effects of dopants in active biomaterials