## 8 Relevant Applications of Melt Electrospinning
### Biomedical Applications and Tissue Engineering
Bones are composed of cortical bone and trabecular bone at different ratios depending on the specific bone. The fibrous tissue that surrounds the outer cortical bone surface is called periosteum and it contains blood vessels, nerve fibers, osteoblasts and osteoclasts, hence it plays a very important role in fracture repair [226] and thus, in bone regeneration. [PERSON] et al. [227] combined a star-shaped PEG heparin hydrogel system loaded with human umbilical vein endothelial cells (HUVECs) with a medical grade PCL tubular scaffold seeded with human Bm-MSCs at an attempt to regenerate the periosteum in mice. These two types of cells were used to mimic both the vascular and osteogenic functions. HUVECs increased the vascularization. However, 30 days after the implantation in vivo, Bm-MSCs retained the undifferentiated state, which could be due to the properties of the hydrogel. The negative charge of heparin caused a slow release of growth factors. Furthermore, host cells gradually replaced human cells. This could be attributed to the species-specific differences between the host and donor cells. PCL has been also applied to manufacture scaffolds for oral hard and soft tissue, i.e., bone and mucosal regeneration. [PERSON] et al. [228] developed multi-layered membranes for an in vitro study. These membranes, composed of specific surface scaffolds for each tissue as well as bacteria-tight core membranes for an infection-free guided tissue regeneration, were manufactured via melt electrowiriting. Since scaffolds with square pores have been previously reported to promote osteoblast and endosteal cell growth [229], a box-structured surface scaffold was designed for the bone side. As for the mucosa tissue, triangular pores were chosen. The result after fusing both scaffolds with the bacteria-tight core membranes was the obtainment of individual bi-layered membranes. Cell growth was finally evaluated by seeding osteoblasts on the box-shaped membrane, and keratinocytes and fibroblasts on the membrane with triangular pores. Results showed these membranes could represent a potential method for bacteria-free wound healing and guided tissue regeneration in oral and maxillofacial surgery. Other applications in tissue engineering where melt electrospinning is employed include articular cartilage regeneration. Cartilage is composed of a dense ECM with highly specialized chondrocytes--the main composition of which is water, collagen, proteoglycans, other non-collagenous proteins and glycoproteins in lower amounts (Figure 14a). The tissue lacks of blood vessels, lymphatics and nerves. Its primary function is the transmission of loads with a low coefficient of friction, hence its surface must be smooth and lubricated [230]. [PERSON] et al. [231] developed a negatively charged star-shaped PEG/heparin hydrogel combined with a medical grade PCL melt electrospun fibrous network. The resulted fibrous-reinforced hydrogel exhibited good mechanical properties and had a microenvironment analogous to the negatively charged proteoglycan matrix of native cartilage, which promoted in vitro necortilage formation when seeded with human articular chondrocytes (Figure 14b). Tendons and ligaments are tissues that connect bone to muscle and bone to bone, respectively. Injuries of these tissues are both common and serious, and their repair represent a current challenge due to their poor natural healing response [232]. For this reason, efforts are being made to find a treatment that helps their regenerate. That is where techniques like melt electrowiriting and melt electrospinning may play a significant role in tissue engineering. Both tissues possess similar ultrastructure and physiology and perform similar functions [233]. The main composition of tendons and ligaments are fibrillar collagens of different types, type I is the predominant one in tendons and contains regions of \(\alpha\)-helices [232] that led to an elastomeric character. In an in vitro approach, [PERSON] et al.