Direct electrical stimulation enhances osteogenesis by inducing Bmp2 and Spp1 expressions from macrophages and preosteoblasts

Abstract

The capability of electrical stimulation (ES) in promoting bone regeneration has already been addressed in clinical studies. However, its mechanism is still being investigated and discussed. This study aims to investigate the responses of macrophages (J774A.1) and preosteoblasts (MC3T3‐E1) to ES and the faradic by‐products from ES. It is found that pH of the culture media was not significantly changed, whereas the average hydrogen peroxide concentration was increased by 3.6 and 5.4 µM after 1 and 2 hr of ES, respectively. The upregulation of Bmp2 and Spp1 messenger RNAs was observed after 3 days of stimulation, which is consistent among two cell types. It is also found that Spp1 expression of macrophages was partially enhanced by faradic by‐products. Osteogenic differentiation of preosteoblasts was not observed during the early stage of ES as the level of Runx2 expression remains unchanged. However, cell proliferation was impaired by the excessive current density from the electrodes, and also faradic by‐products in the case of macrophages. This study shows that macrophages could respond to ES and potentially contribute to the bone formation alongside preosteoblasts. The upregulation of Bmp2 and Spp1 expressions induced by ES could be one of the mechanisms behind the electrically stimulated osteogenesis.

Electrical stimulation in bone tissue engineering treatments

“…Numerous studies have demonstrated that MAPK pathways and the subsequent signaling cascades of ERK1,2, JHK, and p38 are activated by moderate levels of ROS [86]. Proliferation and differentiation of MSC were shown to be mediated by a mild rise in hypoxia-induced ROS [87][88][89].…”

“…Moreover, EStim was shown to significantly enhance macrophage phagocytic uptake and to selectively modulate cytokine production [116]. EStim's effect of upregulating osteogenic gene (Spp2 and Bmp2) transcription in macrophages could help explain its role in stimulating osteogenesis [89]. In vivo, low-voltage EStim was shown to modify macrophage response by changing the M1 to M2 macrophage ratio [97].…”

Electroactive 3D Printed Scaffolds Based on Percolated Composites of Polycaprolactone with Thermally Reduced Graphene Oxide for Antibacterial and Tissue Engineering Applications

“…Moreover, ES has been studied as a potential tool in tissue regeneration to increase the proliferation and differentiation of human stem cells [5,[9][10][11][12][13]. There are several reports in the literature on the use of ES for fracture treatments and tissue repairs using electrical stimulation methodologies, particularly DC or electromagnetic fields [14]. It was established that by applying an electric field (EF), cellular behavior can be modified, including the orientation, proliferation, and rate and direction of cell migration of the corneal, epithelial, and vascular cells, among others [15].…”

Electrical Stimulation through Conductive Substrate to Enhance Osteo-Differentiation of Human Dental Pulp-Derived Stem Cells

“…Similarly, it has been reported that the mineralization of rat bone marrow stromal cells may only be improved when ES is applied at early stage of osteo-differentiation [33]. However, Srirussamee et al have applied ES to pre-osteoblasts (MC3T3-E1), and their results showed that the level of Runx2 expression remains unchanged during the early stage [27]. Because pre-osteoblasts are committed cells, their results implied that ES may mainly promote stem cell differentiation to therefore accelerate mineralization.…”

“…Although the insertion of electrodes to culture medium may easily provide DCEF treatment, this method may elicit unwanted redox reactions of the medium ingredients as well as the faradaic reaction and corrosion of the electrodes [27]. Therefore, we have previously fabricated a conductive polypyrrole (PPy) film to construct an ES device [28].…”