Sequential application of mineralized electroconductive scaffold and electrical stimulation for efficient osteogenesis

Abstract

Osteogenic differentiation is enhanced by many inductive factors including biochemical agents, biomechanical stresses, and electrical stimulation. Regularly studies have focused on one factor at a time, while synergies can promote more effective and functional osteogenesis. Herein, for the first time, functional synergism between application of electrical stimulation and HA nanoparticles was evaluated in osteogenic differentiation. Prepared electrospun biocompatible conductive scaffold by amalgamating chitosan, aniline-pentamer, and hydroxyapatite incorporation was seeded by human bone-marrow-derived mesenchymal stem cells. The cells seeded on the scaffolds with and without hydroxyapatite were exposed to electrical stimulation and subsequently, osteogenic molecular markers and related signaling pathways were investigated. In general, all investigated osteogenic markers (osteocalcin, alkaline phosphatase, osteonectin, and Runx2) were upregulated transcriptionally in the cells seeded on the chitosan-embedded scaffolds. Separate utilization of electrical stimulation or hydroxyapatite-enhanced osteogenesis, while the cells exposed to both stimulators simultaneously, expressed higher levels of some of osteogenic genes significantly. Considering the functions and the positions of the markers in osteogenic signaling pathways, it can be concluded that HA might cooperate in the allocation of stem cells to osteoprogenitors in the early phase of osteogenesis while electrical stimulation helps committed cells with maturation and acquiring functional phenotypes. Altogether investigation of the synergism between different stimulators and exploiting the interactions in an optimized manner could lead to more efficient osteogenesis protocol for effective bone regeneration and tissue engineering. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1200-1210, 2018.

Electro-responsive polymer-based platforms for electrostimulation of cells

“…Thus, it properly deliveries electrical signals to cells and provides a suitable environment to accommodate cells and support their metabolic activities promptly. 1,5,[59][60][61][62] Several electro-responsive polymers are used in the development of advanced conductive cell culture/tissue engineering scaffolds, including those from the conjugated polymer family poly(pyrrole) (PPy), [63][64][65][66] polyaniline (PANI), [67][68][69][70][71] poly(3,4-ethylene dioxythiophene) (PEDOT)), [72][73][74][75] and polysaccharides (chitosan (CS)), [76][77][78][79][80][81][82] hyaluronic acid (HA), 83 and alginate (ALG). 84,85 Conductive scaffolds are also commonly obtained by combining highly conductive carbon-based materials (e.g., carbon nanotubes (CNTs), [86][87][88][89] multiwalled carbon nanotubes (MWCNTs), 79,90,91 graphene (GR), [92][93][94] graphene oxide (GO) 95 and reduced graphene oxide (rGO)) 96,97 with non-conductive polymers such as poly(lactic acid) (PLA), poly(-caprolactone) (PCL), poly(ethylene glycol) (PEG), collagen and its derivatives.…”

“…Several electro-responsive polymers are used in the development of advanced conductive cell culture/tissue engineering scaffolds, including those from the conjugated polymer family poly(pyrrole) (PPy), 63–65 polyaniline (PANI), 66–70 poly(3,4-ethylene dioxythiophene) (PEDOT)), 71–74 and polysaccharides (chitosan (CS)), 75–81 hyaluronic acid (HA), 82 and alginate (ALG). 83,84 Conductive scaffolds are also commonly obtained by combining highly conductive carbon-based materials ( e.g.…”

Roles of electrical stimulation in promoting osteogenic differentiation of BMSCs on conductive fibers

“…The mechanism by which ES promotes cell activities has been widely studied. For bone regeneration, the enhanced osteogenic differentiation of multipotential mesenchymal stromal cells (MSCs) under ES draws concerns . One of the most accepted mechanisms is that ES can increase the influx of Ca 2+ into cells via voltage‐gated Ca 2+ channel, and subsequently the elevated cytosolic Ca 2+ concentration can enhance cellular osteogenic differentiation via activating Ca 2+ ion signaling pathway .…”

“…For bone regeneration, the enhanced osteogenic differentiation of multipotential mesenchymal stromal cells (MSCs) under ES draws concerns. 20,22 One of the most accepted mechanisms is that ES can increase the influx of Ca 2+ into cells via voltage-gated Ca 2+ channel, and subsequently the elevated cytosolic Ca 2+ concentration can enhance cellular osteogenic differentiation via activating Ca 2+ ion signaling pathway. 6,[23][24][25] Some studies also show that ES acts on cells by generating local electrical fields, varying in current/intensity, which can regulate extracellular matrix (ECM) proteins in aspects of their synthesis and secretion, membrane proteins in aspects of location and redistribution, and even depolarize cytomembrane or change the transmembrane potential.…”

Enhanced Cell Proliferation and Osteogenesis Differentiation through a Combined Treatment of Poly-L-Lysine-Coated PLGA/Graphene Oxide Hybrid Fiber Matrices and Electrical Stimulation

“…Thus, electrical stimulation is a widely known adjunctive therapy used to enhance bone healing. More importantly, applying ES combined with composite biomaterials that have excellent biocompatibility will further enhance ES's biological effects, which have great potential in bone defect repair [56]. For the above purpose, in this study, the effect of PLL-PLGA/GO hybrid fiber matrices under ES conditions on MC3T3-E1 cells growth and osteogenesis differentiation was systemically studied.…”