Osteogenic Differentiation of Mesenchymal Stem Cells with Silica-Coated Gold Nanoparticles for Bone Tissue Engineering

Abstract

Multifunctional nanofibrous scaffolds for effective bone tissue engineering (BTE) application must incorporate factors to promote neovascularization and tissue regeneration. In this study, silica-coated gold nanoparticles Au(SiO2) were tested for their ability to promote differentiation of human mesenchymal stem cells (hMSCs) into osteoblasts. Biocompatible poly-ε-caprolactone (PCL), PCL/silk fibroin (SF) and PCL/SF/Au(SiO2) loaded nanofibrous scaffolds were first fabricated by an electrospinning method. Electrospun nanofibrous scaffolds were characterized for fiber architecture, porosity, pore size distribution, fiber wettability and the relevant mechanical properties using field emission scanning electron microscopy (FESEM), porosimetry, determination of water contact angle, measurements by a surface analyzer and tabletop tensile-tester measurements. FESEM images of the scaffolds revealed beadless, porous, uniform fibers with diameters in the range of 164 ± 18.65 nm to 215 ± 32.12 nm and porosity of around 88–92% and pore size distribution around 1.45–2.35 µm. Following hMSCs were cultured on the composite scaffolds. Cell-scaffold interaction, morphology and proliferation of were analyzed by FESEM analysis, MTS (3-(4,5-dimethyl thiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt) and CMFDA (5-choromethyl fluorescein acetate) dye assays. Osteogenic differentiation of MSCs into osteogenic cells were determined by alkaline phosphatase (ALP) activity, mineralization by alizarin red S (ARS) staining and osteocalcin expression by immunofluorescence staining. The results revealed that the addition of SF and Au(SiO2) to PCL scaffolds enhanced the mechanical strength, interconnecting porous structure and surface roughness of the scaffolds. This, in turn, led to successful osteogenic differentiation of hMSCs with improved cell adhesion, proliferation, differentiation, mineralization and expression of pro-osteogenic cellular proteins. This provides huge support for Au(SiO2) as a suitable material in BTE.

How Surface Properties of Silica Nanoparticles Influence Structural, Microstructural and Biological Properties of Polymer Nanocomposites

“…The ALP activity was significantly increased in nanocomposites foil PLDLA/hss-SiO 2 when compared to other nanocomposites foils and polymer-based materials on day 21. Researchers reported that silica-coated nanoparticles stimulate the osteogenic differentiation of bone marrow MSCs in vitro concomitant with the upregulation of ALP activity [ 68 , 69 ]. Nanosilica may induce in vitro osteogenic differentiation of precursor cells, as well as improve in vitro osteogenic formation.…”

Regulation of Stem Cell Differentiation by Inorganic Nanomaterials: Recent Advances in Regenerative Medicine

“…Stem cell transplantation has enabled the cure of many diseases. Based on previous studies, we know that the unique physicochemical characteristics of inorganic NMs greatly influence stem cell fate ( Shao et al, 2018 ; Hashemi et al, 2020 ), and the combination of inorganic NMs and stem cells provides new insights into the treatment of several diseases, such as bone injury and neurological disorders ( Gandhimathi et al, 2019 ; Zhang et al, 2019 ). Inorganic NMs, as vehicles, can effectively deliver soluble factors such as growth factors and cytokines to induce stem cell differentiation, and can also interfere stem cell survival, homing and paracrine behaviors by forming specific patterns with fibrous/hydrogel scaffolds ( Qi et al, 2017 ; Zhang et al, 2019 ).…”

“…Inorganic NMs exert their influence on stem cell behavior as unique biomolecules, besides that, as modifiable non-viral transfection vectors, inorganic NMs can carry various bioactive molecules that regulate stem cell behavior, including RNA, plasmids, proteins, or polypeptides, etc., thereby further stimulating the proliferation, migration, differentiation and paracrine behavior of stem cells. Various inorganic NMs, including graphene ( Rostami et al, 2020 ), carbon dots ( Shao et al, 2017 ), gold nanoparticles (AuNPs) ( Heo et al, 2014 ), silver nanoparticles (AgNPs) ( Wan et al, 2020 ), nano titanium-based alloys ( Jalali et al, 2020 ), strontium nanoparticles ( Hu et al, 2017 ), iron oxides nanoparticles ( Zhang et al, 2020 ), manganese dioxide (MnO 2 ) nanoparticles ( Wang et al, 2017 ), silicon dioxide (SiO 2 ) nanoparticles ( Gandhimathi et al, 2019 ), and black phosphorus (BP) nanosheets ( Xu et al, 2020 ), have been extensively explored in stem cells regeneration medicine. The stiffness, size and shape of inorganic NMs can directly affect the bioactivity of materials and, in turn, affect the differentiation of stem cells ( Huang et al, 2020 ).…”

“…Therefore silicon holds great promise for osteoporosis therapy ( Price et al, 2013 ). SiO 2 can enhance the hydrophilicity of nanofibers and favor the adhesion and growth of MSCs, which in turn promote osteogenic differentiation ( Gandhimathi et al, 2019 ).…”

Usefulness of a Nanostructured Fibrin-Agarose Bone Substitute in a Model of Severely Critical Mandible Bone Defect

“…In this study, we used an HTEB substitute containing human cells pre-differentiated to the osteoblastic cell lineage using previously described induction methods. Despite the fact that these methods are broadly used to induce osteogenic differentiation, and are known to be highly efficient [25], future studies should analyze the phenotype of these cells using enzymatic methods, such as the alkaline phosphatase (ALP) activity assay [37].…”