Table 3.

Mechanisms by which electroactive scaffolds or electrical stimuli promote bone healing and regeneration

Enhancement of osteogenesis	Focal adhesion (FA) associated mechanotransduction signaling pathway	Raic et al.[ 108 ] Shen et al.[ 109 ] Ribeiro et al.[ 110 ]
	Voltage‐gated Ca2+ channels	Bagne et al.[ 111 ] Zhuang et al.[ 112 ] Brighton et al.[ 113 ]
	Connexin 43 mediated influx of Ca2+	Park et al.[ 114 ]
	Calcineurin/NFAT signaling	Winslow et al.[ 115 ] Wang et al.[ 116 ]
	Protein Kinase C (PKC) signaling	Shen et al.[ 109 ] Liu et al.[ 117 ]
Enhancement of angiogenesis/vascularization	Secretion of VEGF and other pro‐angiogenic cytokines	Fonseca et al.[ 124 ] Tzoneva et al.[ 126 ] Bai et al.[ 129 ]
	ERK/MAPK signaling	Sheikh et al.[ 125 ]
	Akt – ERK1/2 – JNK signaling axis	Chen et al.[ 127 ]
	PI3K – Akt/Rho‐ROCK signaling axis	Zhao et al.[ 128 ]
Inhibition of osteoclastogenesis and bone resorption	Mechanisms unclear
Immunomodulatory effects	Monocytes and macrophages migrate away from electrical stimuli	Leppik et al.[ 138 ] Kearns & Thompson[ 139 ]
	Enhancement of macrophage phagocytic uptake	Hoare et al.[ 140 ]
	Promote transition of macrophages from pro‐inflammatory M1 to pro‐healing M2 phenotype	Dai et al.[ 141 ] Li et al.[ 142 ] Jiang et al.[ 143 ]
Anti‐bacterial effects	Electropermeabilization via disruption of Na+/K+ pump	Valic et al.[ 146 ]
	Electropermeabilization via stress induction on teichoic acid of bacterial cell wall	Rauch & Leigh[ 147 ]
	ROS generation	Jeong et al.[ 148 ] Feng et al.[ 149 ]
	Disruption of bacteria respiratory chain	Wang et al.[ 150 ]