## 3 Electrospinning
### Biomimetic Applications of Electrospun Nano Structures for Tissue Engineering Purposes  
The tissue engineering application of the electrospun nanofibrous scaffolds is attributed to its ability to mimic the biological environment (BM or ECM) which provides both the biochemical and biophysical information required for efficient cell adhesion, proliferation, differentiation and migration [48; 49; 50]. This biomimetic ability of the electrospun scaffold has been harnessed in the field of tissue engineering to regenerate various tissues such as muscle, bone, skin, cartilage, nerve, ligament and liver [48; 50; 49]. Biomimetic nanofibrous scaffolds produced by electrospinning can be broadly classified into three major types based on the type of polymer used: electrospun nanofibrous scaffolds based on natural polymers, scaffolds fabricated from synthetic polymers and scaffolds made by co-spinning both natural and synthetic polymers [54]. Electrospun nanofibers of 500-800 nm diameter with high porosity and effective mechanical property were produced by [PERSON] et al. using poly (lactic-co-glycolic acid) (PLGA) [55]. They showed that the nanofibers promoted cell adhesion due to their close resemblance to the nanoscale environment of the extracellular components [55]. This preference for cells to adhere and spread in nanoscale fibers was also observed in mouse fibroblast cells seeded on PLGA nanofibers and smooth muscle cells seeded on PLCL clearly indicating that the nano-topography of the BM and the ECM has to be replicated in vitro to successfully influence cell adhesion, proliferation, and phenotypic behavior [55; 56]. Poly (\(\varepsilon\)-caprolactone) (PCL) is another synthetic thermoplastic polymer that is extensively used in tissue engineering to make nanofibrous scaffold. Cells seeded on PCL nanofibers have displayed maturation and differentiation [54]. For instance, fetal bovine chondrocytes matured and started expressing type II collagen when seeded on to PCL nanofibers. Similarly, human marrow stromal cells differentiated into different cell lineages (adipogenic and chondrogenic) based on the type of culture media, when seeded on nanofiber PLC scaffolds [57; 58]. The nanofibers made of natural polymers not only mimic the nanoscale topography of the BM and ECM components but also it has the inbuilt biological and chemical properties for cell adhesion and growth. Collagen is one such example, which is one of the most abundant structural proteins in vertebrates [59]. It is made up of three long polypeptide chains twisted to each other in a triple helix structure providing it with its characteristic mechanical strength and elasticity [57]. Collagen types I, II, III and IV are commonly used to make nanofibrous scaffolds [59; 60]. Collagen nanofibers of diameters 250 nm (type III) and 100 nm (type I) were produced by [PERSON] et al., which exhibited successful adhesion and penetration of aortic smooth muscle cells. He observed that the property of the fibers largely depends on the type of collagen used [61]. Moreover, they exhibited successful adhesion and penetration of aortic smooth muscle cells into the engineered matrix. Collagen IV in hexafluoroisopropanol (HFIP) solvent also demonstrated the production of fibers in a size range from 100 nm to 2 \(\upmu\)m [62]. To increase the stability, elasticity and tensile strength of the collagen fibers, crosslinking agents such as glutaraldehyde, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and genipin (natural crosslinking agent from fruits of _Gardenia jasminoides_) are also in use [52; 60]. Similarly, other natural polymers such as gelatin (denatured collagen), elastin (a structural protein in the ECM of connective tissue), silk fibroin, fibrinogen (plasma serum protein), laminin, chitin, and chitosan are also used to successfully produce electrospun nanofibers, and as scaffolds for efficient cell growth [60]. Natural polymers are biocompatible with inherent cell adhesion properties and are less immunogenic when compared to synthetic polymers [47].