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Optimised Vascular Network for Skin Tissue Engineering by Additive Manufacturing Alper Ekinci, Xiaoxiao Han, Richard Bibb, and Russell Harris

1.1 Introduction Many clinical therapies utilise autologous and allografts to repair skin defects resulting from genetic disorders, acute trauma, chronic wounds or surgical interventions. Tissue engineering (TE) of skin is an emerging technology that offers many potential advantages in repairing skin defects over conventional autologous grafts [1]. It overcomes the shortage of donor organs and reduces the added cost and complications of tissue harvesting. Tissue-engineered skin can also be used as a skin equivalent for pharmaceutical or cosmetics testing, eliminating the need for animal testing [2]. A major issue in tissue engineering is that the artificial skin may not develop adequate vascularisation for long-term survival [3]. An artificial vascular system can be pre-embedded in a skin equivalent before it is implanted. The embedded network has three primary functions: (1) to supply nutrients and other soluble factors and to remove waste products from the surrounding cells, (2) to act as scaffolds for culturing vascular endothelial cells and (3) to develop

A. Ekinci Wolfson School of Mechanical, Electrical and Manufacturing Engineering, Loughborough University, Loughborough, UK e-mail: [email protected] X. Han () HNU College of Mechanical and Vehicle Engineering, Hunan University, Changsha, China e-mail: [email protected] R. Bibb Design School, Loughborough University, Loughborough, UK e-mail: [email protected] R. Harris Mechanical Engineering, University of Leeds, Leeds, UK e-mail: [email protected] © Springer Nature Switzerland AG 2021 B. Bidanda, P. J. Bártolo (eds.), Virtual Prototyping & Bio Manufacturing in Medical Applications, https://doi.org/10.1007/978-3-030-35880-8_1

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small sprouting capillaries that can be connected with existing blood vessels, also known as angiogenesis [1, 4–6]. Nutrition supply in the human body is realised by a very complex blood vessel network. It consists of vessels in dimensions between several millimetres down to several micrometres in diameter. To mimic the system, flexible structuring processes are needed. Traditional manufacturing technologies, such as spinning, dip-coating or extrusion, can produce linear tubes with different inner-diameters [7]. However, it is not possible to generate branched vessels, with decreasing or increasing internal diameters to mimic the natural changes in blood vessel networks. Additive manufacturing (AM) technologies have made it possible for the first time to manufacture artificial blood vessels and their networks of any sophisticated geometry and connections. With AM, three-dimensional (3D) objects can be produced from 3D computer-aided design (CAD) data by joining materials together using a layer-by-layer manner. There are many AM technologies classified as bioprinting systems, based on microvalve deposition, ink-jetting, material extrusion and stereolithograp