## 1 Introduction  
Physiologically, each cell and organ has a position in three dimensions. In vivo, the cells in each tissue can interact with other cells in every available direction, unlike _in vitro_ cell cultivation. To restore the cellular properties to restricted cell culture systems, a spherical formation is commonly used to enhance and restore cellular function [1, 2]. It is well known that cells lose their regenerative potential during _in vitro_ cultivation [3]. However, three-dimensional cultivation, especially in a spherical shape, is used in maintaining cellular potential and properties to differentiate functionally [4, 5]. Human hair follicle dermal papilla cells (DPCs) can be cultured in a spheroid for the induction of hair-follicle neogenesis [6, 7]. Hair follicles are known to have cyclic interaction between the epithelial compartment and mesenchymal compartment [8; 9]. In the proliferation stage--called anagen--the epithelial cells (matrix cells) around the DPCs are highly proliferative and differentiate into the components of the hair shaft. It is assumed that dermal papilla cells interacting with epithelial population control the initiation of the hair cycle and the maintenance of the duration of anagen [10]. Intriguingly, during the mature anagen stage, the time of the hair follicle growth, DPCs are not proliferative compared to proliferative matrix cells in the hair follicle. DPCs are highly regulated autonomously; the cells from the connective tissue sheath join DPCs and proliferate in early anagen [11; 12; 13]. After this stage, the total number of DPCs are strictly maintained during mature anagen [14]. These DPCs provide instructive signals required to activate and initiate hair follicle regeneration [15]. Though dermal papilla is an important component in the biology of the hair follicle, the scientific research is mainly focused on the characteristics of DPCs in _in vitro_ cultivation, especially in humans because of lack of experimental tools [16; 17]. Previously, it was reported that human DPCs in spherical form have the potential to generate a new hair follicle combined with trichogenetic neonatal mouse competent epithelial cells in a hair induction assay [18]. In rat, even cultured DPCs can make new hair follicle [19]. However, it is reported that after DPCs are removed from the hair follicle in vivo, they tend to lose their ability to make new hair follicles in cultivation [20]. Though the DPCs are known to lose this ability after serial passage, it is reported that factors such as Bone Morphogenetic Protein (BMP) and keratinocyte-conditioned media can maintain their ability after cultivation [20; 21]. Furthermore, DPCs in spheroid have been reported that were similar to in vivo DP morphologically and in DP signature. These 3D spheres can induce human follicle formation [6; 7]  
Recently, it was also shown that the spherical formation generated by a hydrocell binding plate could restore the ability of human hair DPCs to perform neogenesis [18]. Applying a hydrocell plate to human cell therapy, however, has critical drawbacks. First, handling each dermal papilla sphere by hand is burdensome and thus would be difficult to commercialize or mass production for clinical use in patients. Second, it is not possible to control the size of the spheres generated because their size is highly dependent on the quality of each hydrocell plate; therefore, homogeneously sized spheres cannot be easily produced. Third, the control of the cellular density is impossible because the mechanical forces from hydrocell plates can prevent cellular aggregation. Because of these inescapable forces, the size of the sphere is proportionated to the total number of cells inserted inside the plate. To overcome the weaknesses of using a hydrocell plate, we generated a spherical formation using the alginate and electrospinning method [22]. Using this method, spheres can be produced not only homogeneously but also without dealing with each individual cell by hand [23].