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Additive Biomanufacturing Processes to Fabricate Scaffolds for Tissue Engineering Boyang Huang, Henrique Almeida, Bopaya Bidanda, and Paulo Jorge Bártolo

5.1 Introduction Tissue engineering is a rapidly expanding multidisciplinary and interdisciplinary field exploiting biocompatible and biodegradable materials, living cells, and biomolecular signals combined with additive manufacturing approaches to produce constructs to restore, maintain, or enhance the function of tissues or organs [1–8]. Three strategies have been explored for the creation of a new tissue [3, 4, 9– 15]: • Strategy 1: The use of isolated cells or cell substitutes. This strategy, widely used in clinical applications such as cornea, oesophagus, heart periodontal ligament and cartilage, avoids potential surgical complications but has the disadvantages of possible rejection or loss of function (in vivo). • Strategy 2: Delivery of tissue-induced substances such as low-molecular-weight drugs, proteins and oligonucleotides that can stimulate cell proliferation, migration and differentiation. These signalling molecules are generally divided into: (1) mitogens which stimulate cell division, (2) growth factors which mainly induce cell proliferation, and (3) morphogens that control tissue formation. The

B. Huang · P. J. Bártolo () School of Mechanical, Aerospace and Civil Engineering, The University of Manchester, Manchester, UK e-mail: [email protected]; [email protected] H. Almeida School of Technology and Management, Polytechnic Institute of Leiria, Leiria, Portugal e-mail: [email protected] B. Bidanda University of Pittsburgh, Department of Industrial Engineering, Pittsburgh, PA, USA 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_5

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Fig. 5.1 Bottom-up and top-down approaches

success of this strategy depends on the growth factors and controlled released systems (in vitro). • Strategy 3: Cells placed on or within constructs. This is the most common strategy and involves two approaches: bottom-up and top-down (Fig. 5.1). The bottom-up approach employs different techniques for creating modular tissues, which are then assembled into engineered tissues with specific micro-architectural features [16–18]. Tissue modules can be created through selfassembled aggregation, microfabrication of cell-laden hydrogels, fabrication of cell sheets, or direct printing [19–22]. The ability of cell aggregates to fuse is based on the concept of tissue fluidity, according to which embryonic tissues can be considered as liquids [23]. The major drawback of this approach is that some cell types are unable to produce sufficient extracellular matrix (ECM), migrate or form cell–cell junctions [14]. The top-down or scaffold-based approach is based on the use of a temporary scaffold that provides a substrate for implanted cells and a physical suppor