# Fibers by Electrospinning and Their Emerging Applications in Bone Tissue Engineering
## 2 ECM Simulation
Chitosan island-like structure provides a controllable balance of the surface hydrophilicity and hydrophobicity, suitable roughness at the surface for cell adhesion and cell recognition sites. This work presented a novel scaffold surface design. Although the temperature of jets affects the surface of scaffolds, the electrospinning method to control mesh architecture and composition could also establish a specific ECM for scaffolds. [PERSON] et al. [45] designed multifunctional scaffolds by controlling the speed of electrospinningning solution during co-spinning progress (Figure 3). They set PCL as the outer face to provide mechanical strength and gelatin loaded with hydroxyapatite (HAP) as the inner face to provide cell affinity and osteoconductivity. From the outer to the inner, the content of PCL decreased while the content of gelatin increased. The fiber diameter and alignment affect interaction of the scaffold with cells [128; 129; 130]. Based on earlier work, [PERSON] et al. [42] designed a group of controlled experiments. The results verified that alignment and decreased diameter of fibers had clear advantages in promoting proliferation and migration and facilitating the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) compared with normal fibers. Scaffolds with random structure prevent effective cell infiltration. Therefore, to overcome this disadvantage of traditional electrospinningning, [PERSON] et al. [41] created a modified electrospinningning process called 3D jet writing. This modified process was demonstrated to create precisive 3D structures to offer customizable pore geometries (Figure 4). Precisive structures are achieved via stable jetting supported by a secondary electrode. Compared with a conventional process, this work reported a novel process to fabricate precisive scaffolds. In general, the scaffold built by electrospinning has a native ECM-like physical structure with high surface area. However, limited pore sizes are the obstacles for cell infiltration  
Figure 4: (**a**) The illustration of the 3D jet writing setup; (**b**) the SEM image of the fibrous scaffolds made by 3D jet writing. Reprinted from [41], with permission from Wiley. © 2021 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Figure 3: Preparation of multifunctional scaffolds via controlling the speed of electrospinninging solution during co-spinning progress. Reproduced with permission [45]. © 2021 Wiley-VCH GmbH. Figure 2: The illustration of preparation of a bicomponent scaffold with island-like structure formed from PLA and chitosan (CS). Reproduced with permission [86]. Copyright © 2021, American Chemical Society. to the scaffold [131]. Various strategies were employed to modify the surface of electrospun scaffolds. It was reported that HAP crystals could be bound to the acidic amino acid peptide domains [132]. Based on early study, [PERSON] et al. [105] prepared the silk fibroin (SF)/PCL scaffolds and immersed them in simulated body fluid to mineralize the scaffolds. As the seven amino acid glutamate sequence (E7) could improve peptide coupling to HAP [133], they coupled mineralized scaffolds with E7-BMP-2. Aside from this method, [PERSON] et al. [58] used NHS-EDC (NHS, N-hydroxysuccinimide; EDC, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide) amide reaction to couple E7-BMP-2 onto the PCL scaffolds. The results of these two works showed that modified scaffolds had a better performance in cell adhesion than unmodified ones. To improve the ability of the scaffold for modulating human pluripotent stem cells (hPSCs) differentiation toward osteoblastic phenotype, [PERSON] et al. [63] also combined electrospun PCL scaffold with vitronectin (VN) peptide conjugation via NHS-EDC amide reaction. It was reported previously that PLLA fibrous scaffold with high surface area was fabricated by a two-step strategy [134; 135]. Based on this strategy, [PERSON] et al. [30] fabricated porous PLLA/dopamine (DOP)/amorphous silica nanoparticles (SiNPs) scaffolds with high surface area (Figure 5).