## 8 Relevant Applications of Melt Electrospinning
### Biomedical Applications and Tissue Engineering  
If melt electrospinning is at the dawning, the technique applied in tissue engineering has to come a long way to see the first sunrays. For this reason, most papers in this field discuss experiments performed in vitro. Very few have reached the in vivo or clinical stages. Nevertheless, tissue engineering and the requirements that engineered constructs must meet have been vastly studied for more than 30 years [185; 186; 187]. Generally, tissue engineering is used to repair and/or regenerate damaged tissues and organs [15]. 3D nanofibrous structures, namely scaffolds [188], that mimic the structure and function of the natural extracellular matrix (ECM) [189] are manufactured and, by means of melt electrospinning or melt electrowriting, a wide range of fiber diameters can be achieved as well as well-defined and controllable geometries and porosities. As the temporary substitutes they are, scaffolds must provide the appropriate microenvironment to promote cell adhesion, migration, proliferation, differentiation and secretion of cells own ECM [190; 191; 192], and eventual formation of the tissue or organ [193]. These processes can be induced mechanically or chemically, or by the scaffold structure, which can regulate the cell alignment [194; 195]. In mechanical induction, press [196], tensile [197], or shear [198] stress are applied on cells to induce polarization, whereas in chemical induction, growth factors are used to attract cell penetration [199]. The design of the scaffold and the selection of growth factors are based on the damaged tissue (e.g., vascular, endothelial, adipose, skin, muscle, cartilage, and bone) that is wished to repair [200]. Moreover, not only are there differences among each type of cell or tissue and how it interacts with the scaffold [161], but cellular invasion also depends on whether the experiment is being carried out in vitro or in vivo, especially due to the vascularization [201; 202]. The diffusion limit of oxygen and nutrients within tissues is found to be between 150-200 \(\upmu\)m. Most tissues rely on blood vessels for the transport of oxygen and nutrient supply [203; 204], hence, control over vascularization is so important in larger tissues, as the nearest capillary should never exceed that distance [205; 206]. Vascularization of scaffolds prevents necrosis of tissues and is achieved by spontaneous vascular ingrowth as a response to hypoxia that implanted cells secrete [207]. In vitro cultures can also be supplied with nutrients and oxygen in certain bioreactors [208]. However, not everything is \"a piece of cake\". The capillary growth is limited to tenths of micrometres per day [209] and doing  
Figure 13: The fabrication and performance of functional electrospun materials for food packaging applications. EO, essential oil. Copyright 2020 Elsevier [183]. the calculations, this means weeks are needed to complete the vascularization in implants in the order of millimeters. This could not only lead to hypoxia and an eventual necrosis of the tissue, but also to a non-uniform cell differentiation and thus, a decreased tissue function [210]. Therefore, vascularization is a current challenge that needs to be overcome or circumvented [211]. Melt electrospinningning and preferably melt electrowriting, most inherent problems could be tackled as scaffolds design parameters, including structure, shape, size, porosity [212], and fiber diameters and spacings [213,214] can be adjusted according to the needs of the tissue in question. This is one of the main advantages of using molten polymers: these are often viscous and nonconductive, avoiding this way electrical instabilities in electrospinning jets. The technique allows a predictable fiber deposition, a layer-by-layer fabrication of scaffolds with defined designs, shapes and thicknesses [202]. In an in vitro study performed by [PERSON] et al.