# Fibers by Electrospinning and Their Emerging Applications in Bone Tissue Engineering
## 2 ECM Simulation  
ECM simulation is a key part of BTE. ECM provides the tissue with growth factors and nutrients for controlling cell proliferation and differentiation under a special environment [112, 113, 114]. To meet the requirements of BTE, the fibrous scaffold prepared by electrospinning should not only provide structure and mechanical robustness for the tissue, but also mimic native ECM for bone tissue repair. Three methodologies are employed to achieve this goal, i.e., (1) selection of scaffold components, (2) improvement of spinning methods, and (3) processing after spinning. In BTE, several natural and synthetic polymers (shown in Table 2) are electrospun because of their biocompatibility. Electrospinning can be defined as an electrohydrodynamic process: when the potential energy formed by the potential difference is higher than the surface tension of the polymer solution, a Taylor cone is formed from a spherical droplet under the applied voltage; then, the polymer solution will be mechanically stretched under the action of the electric field and form fibers with solvent evaporation [115, 116]. The performance of the fibers mainly depends on the inherent properties of polymers. Piezoelectricity is one of the inherent properties of bone, attributed to the piezoelectric effect of the crystalline micelle of collagen [117]. The electrical signals produced by bone promotes \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Metrices** & **Feature** & **Ref.** \\ \hline \multirow{8}{*}{Synthetic polymers} & \multirow{4}{*}{PCL} & Biocompatible, bioresorbable and cost & [12, 14, 15, 16, 17, 18, 19, 22, 24, 25, 29, 31, 32, 38, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79] & [12, 14, 15, 16, 17, 18, 19, 22, 24, 25, 29, 31, 32, 38, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79] & [30, 42, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93] \\  & & & \\  & & & \\  & & & \\  & & & & \\  & & & & \\  & & & & \\  & & & & \\  & & & & \\  & & & & \\  & & & & \\  & & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Examples of electrospun polymeric matrices used in BTE. bone growth and remodeling [118]. Poly (vinylidene fluoride) (PVDF), a kind of piezoelectric materials in BTE, has high hydrophobicity which is not conducive to cell adhesion and cell proliferation. [PERSON] et al. [119] found that the piezoelectric electrospun nanofibers enhanced cell activation confirmed by intracellular calcium imaging. According to this discovery, they combined the advantages of both electrospinning and plasma treatment to develop a 3D tissue-like functional self-sustainable scaffold for BTE. Because of piezoelectricity, the scaffold released a piezoelectric potential. It stimulated the voltage-gated calcium channels (VGCC) in the cell membrane and caused cell activation (Figure 1) [120]. The results showed that a functional and stable hydrophilic scaffold could be fabricated by the combination of a highly \(\beta\)-phase electrospun PVDF with oxygen plasma treatment. [PERSON] et al. [33] used electrospinning process to fabricate 3D hybrid scaffolds based on piezoelectric poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). It was discovered, compared with non-piezoelectric polycaprolactone (PCL) scaffolds, 3D hybrid scaffolds revealed more superior osteoinductive properties because of the improvement of degree of mineralization and adhesion promotion of human mesenchymal stem cells (hMSCs). The extent of cell-substrate interaction is an important factor in evaluating the effect of the microenvironment of the scaffolds. ECM is composed of structural proteins, polysaccharides, and adhesive proteins [121]. Tissue engineering scaffolds can be also made by the decellularized ECM (dECM). Embedding dECM into synthetic polymers is an effective strategy. The microenvironment enriched with dECM biochemical cues could stimulate cells to regenerate bone. [PERSON] et al.