# Fibers by Electrospinning and Their Emerging Applications in Bone Tissue Engineering
## 1 Introduction  
Bone defects, caused by tumors, trauma, and infections, have posed serious challenges for clinical treatment. Among traditional methods, autograft transplantation is regarded as the \"gold standard\" for repairing critical-sized bone defects without adverse immune response due to its significant osteoinductivity and osteoconductivity [1]. However, the use of autografts also suffers inevitable drawbacks, such as limited clinical availability, multiple operations, and morbidity at the donor site [2, 3]. Moreover, allogeneic bone transplantation has caused disease transmission and immunoreaction, which are seriously concerned. Therefore, bone tissue engineering (BTE) has been introduced as an optimized method for bone regeneration to overcome the shortcomings of lacking donors. An ideal BTE scaffold should exhibit biocompatibility, biodegradability, and suitable mechanical strength, and imitate the extracellular matrix (ECM) to regulate cell behavior [4]. Fibrous scaffolds are considered to enhance cell adhesion due to high specific surface area. There are various techniques employed to fabricate fibrous scaffolds, such as self-assembly [5], phase separation [6], and electrospinning [7]. Electrospinning is a simple technique to prepare fibers with diameters ranging from nanoscale to micron by uniaxial stretching of the charged jet. This technique has attracted great attention because of its efficiency, adaptability, and flexible preparation of electrospinning solution. Owing to these remarkable features, electrospun fibers have been widely used in different fields [8]. Recently, different kinds of electrospinning processes were proposed and optimized to achieve favorable structures and properties, as shown in Table 1.  
During the process of electrospinning, the morphologies and properties of electrospun fibers are directly affected by various parameters. These parameters significantly influencethe spinability, diameter, and orientation/alignment of fibers. Spinnability, defined as the ability of polymers to form stable fibers, mainly depends on solution parameters including surface tension, viscosity, and conductivity [8]. Surface tension is affected by solvent and concentration of polymer solution. The uniaxial stretch of a charged jet is hardly achieved with low surface tension. Viscosity, determined by the molecular weight of polymer and concentration of polymer solution, also affects spinnability due to polymer chain entanglement. In addition, temperature is a notable factor affecting viscosity. By adding salts, conductivity is increased to help optimize the formation of fibers. The diameter of fibers is affected by the molecular weight of polymer, concentration of polymer solution, instrumental parameters (voltage, flow rate, tip to collector distance), and humidity. The diameter of fibers can be controlled by adjusting the applied voltage and enhancing the stretching of polymer solution. Meanwhile, the flow rate of polymer solution should be optimized to match the applied voltage for uniform fibers. Moreover, different orientation or alignment of fibers can be achieved by selecting different types of collectors like drum, disk, plate, or other customized collectors. In recent years, there have been many attempts combining electrospinning methods with BTE scaffolds. Electrospun fibers, exhibiting similar topological features with ECM, were employed to provide a suitable environment for the adhesion and growth of cells [9]. Furthermore, without any chemical cues, the fiber structure is able to promote osteogenic differentiation in vitro [10]. In order to satisfy the requirement of BTE scaffolds, various polymers have been applied for preparing electrospun fibers. Table 2 shows examples of natural and synthesized polymers used as matrices of electrospun fibrous scaffolds.