# Fibers by Electrospinning and Their Emerging Applications in Bone Tissue Engineering
## 2 ECM Simulation
DOP was applied to modify the surface of PLLA fiber and provided active functional groups. The interaction between PLLA fibers and silica nanoparticles (SiNPs) was enhanced by covalent and non-covalent bonding from polydopamine (PDA), which was made from DOP via oxidative self-polymerization. It not only improved the mechanical properties and hydrophilicity of PLLA/DOP/SiNP hybrid scaffolds, but also enhanced the biocompatibility of the scaffolds. The scaffolds showed great biocompatibility and abilities of cell adhesion and proliferation. It is known that native ECM includes collagen, laminin and glycosaminoglycans, and these macromolecules could be physically absorbed or chemically conjugated onto scaffolds for improving bioactivity [136]. [PERSON] et al. [54] cultured Rabbit articular chondrocytes (rACs) on PCL scaffolds, then generated dECM-coated PCL scaffolds through decellularization treatment. With native ECM macromolecules, the scaffolds had a great effect on cartilage tissue repair. Moreover, in order to mimic the morphological trait and chemical composition of ECM, [PERSON] et al. produced HAP/collagen (Col)-coated poly (lactic-co-glycolic acid) (PLGA) scaffolds via an electrospinning and biomimetic process [97]. In vitro experiment and ALP activity results demonstrated that HAP/Col coating layer improved the interaction between cells and scaffolds. 3D printing has been applied in producing scaffolds for tissue regeneration [137]. Compared with other approaches, 3D printed scaffolds have many advantages including flexibility in design, capability of generating specific shapes, and making highly precisive pores. [PERSON] et al. [50] combined the advantages of both electrospinning and 3D printing, and the fibrous scaffolds prepared by electrospinning were successfully covered onto the surface of 3D printed scaffolds. They reported a simple and versatile method to decorate 3D printed scaffolds with bioactive electrospun fibrous segments. Three-dimensional structure scaffold necessitates an interconnected network and a stable framework. A 3D porous scaffold with the characteristics of open cellular structure,  
Figure 5: The surface of PLLA fiber is modified by DOP. With polymerization of PDA made from DOP via oxidative self-polymerization, the interaction between PLLA fibers and SiNPs is built. Reprinted from [30], with permission from Elsevier. © 2021 Elsevier B.V. All rights reserved. reversible compression, and controllable shape was fabricated by [PERSON] et al. via electrospinningning and freeze drying [82]. In order to establish a network structure, crosslinking is essential. Instead of glutaraldehyde, they chose citric acid as a crosslinking agent based on its characteristics of biocompatibility and nontoxicity. Citric acid plays a key role in inducing and stabilizing the growth of HAP during mineralization. As expected, the 3D porous PLA/regenerated cellulose scaffold with high biological activity possessed both dual porous structure and dimensional stability. On the other hand, [PERSON] and [PERSON] developed an approach to build 3D electrospun fibrous scaffolds named thermally induced nanofiber self-agglomeration (TISA) [138]. Briefly, 3D electrospun fibrous scaffolds were made from short individual nanofibers converted from electrospun fibers (Figure 6). In addition, [PERSON] et al. [29] combined the TISA technique and freeze-drying method to prepare 3D electrospun PCL/PLA nanofibrous scaffolds. Compared with 3D electrospun PCL nanofibrous scaffolds, PCL/PLA-3D scaffolds improved the cell viability and osteogenic differentiation of hMSCs. Based on this work, [PERSON] et al. [56] explored the effect of content of PLA on the properties of PCL/PLA-3D scaffolds. With the increase of PLA content, stiffness and bioactivity were improved, which resulted in the increase of the ALP activity, calcium content, and gene expression level. Furthermore, [PERSON] et al. reported a 3D electrospinningning technique to create 3D PLA scaffolds with the support of lactic acid (LA) [92; 139].