# Fibers by Electrospinning and Their Emerging Applications in Bone Tissue Engineering
## 2 ECM Simulation
mixed bone-dECM with PCL and fabricated bioengineered scaffolds by electrospinning which simulated the native environment of tissue [73]. The wettability, water absorption ability, and surface roughness of the scaffold were enhanced by adding bone-dECM. It was shown in alkaline phosphatase (ALP) and gene expression results that bone-dECM affected the osteogenic differentiation. Furthermore, they found that the bone-dECM particle-integrin interaction induced by the cell adhesive proteins regulated the intracellular processes and enhanced the cell adhesion/migration. [PERSON] et al. [61] used sequential electrospinning with PCL solution containing either  
Figure 1: The piezoelectric potential created by piezoelectric electrospun nanofibers stimulates VGCC in the cell membrane and causes cell activation. Reproduced with permission [119]. Copyright © 2021, The Royal Society of Chemistry. osteoblast or endothelial cells-derived dECM to fabricate two-layer scaffolds. The nanofibrous scaffolds incorporated with angiogenic and osteogenic cues could stimulate bone growth. This work incorporated angiogenic and osteogenic cues into scaffolds to provide the microenvironment that supported osteoblast and endothelial cells in bone regeneration and vascularization. Aside from adding dECM, adding hyaluronic acid or phospholipids can also optimize the microenvironment of the scaffold. [PERSON] et al. [22] combined electrospinningning, molecular self-assembly, and molecular recognition motifs to develop a multi-component approach. They followed this approach to fabricate a composite scaffold composed of PCL and hyaluronic acid incorporated with a short self-assembling peptide. The resultant scaffold was similar to the fibrillar structure of ECM in morphology and showed biocompatibility. The results of ALP and degree of biomineralization confirmed that the fibrous scaffold facilitated osteogenic differentiation. [PERSON] et al. [84] mixed poly (L-lactic acid) (PLLA) and lecithin to fabricate fibrous scaffolds, which offered a strategy for tissue engineering. To improve hydrophilicity and cytocompatibility of PLLA scaffolds, bioactive lecithin was incorporated into polymer solution. PLLA/lecithin scaffolds made a great interaction with cells which induced cells on scaffolds to maintain morphological shape and integrate with the fibers to build a 3D network. Nanoscale building blocks mixed into polymer solution could change the function and shape of fibers in order to meet the application requirements of various fields [122; 123; 124; 125]. [PERSON] et al. [126] combined electrospinningning with doping to fabricate molybdenum disulfide (MoS\({}_{2}\)) composite nanofibrous scaffolds. The MoS\({}_{2}\) composite scaffolds gave cells the platform to maintain activity and provided positive promotion to regulate cell proliferation and osteogenic differentiation. [PERSON] et al. [70] fabricated PCL scaffolds doped with bioactive glasses. In order to enhance the cell response to the fibrous scaffolds, they embedded bioactive glasses with different compositions into the matrix, and the results showed that the composite scaffold had higher abilities in cell adhesion and proliferation compared with neat PCL scaffolds. In addition to scaffold components, the topographic structure is also a key factor to mimic ECM for scaffolds [127]. By combining the advantages of polylactic acid (PLA) and chitosan, [PERSON] et al. [86] prepared a bicomponent scaffold with island-like structure (Figure 2). Automatic phase separation between two incompatible polymers happened during the electrospinningning process. With the quick speed of evaporation of structure under a high temperature in jets, there was not enough time for chitosan molecular chain migrating to the surface of electrospun jets to cover the fibrous shell, which resulted in the formation of the intermittent islands structure.