Additive Manufacturing of Novel Ceramic-Based Composite Scaffolds for Bone Tissue Engineering (original) (raw)

IV The author conducted a portion of the experimental work; optimisation of the printing parameters of the scaffolds; mechanical characterisation; and writing of some sections of the initial draft. 1.1.1 Synthetic scaffolds for BTE Critical-sized bone defects, commonly in the range of 1-4.5 cm are generally repaired by synthetic grafts known as scaffolds (Schemitsch, 2017). To overcome the shortcomings of natural bone scaffolds, a permanent, reliable, sustainable, and holistic solution is required to heal and repair critical-sized bone defects. Synthetic bone scaffolds play an imperative role in BTE and can mimic the natural bone ECM by facilitating and providing a 3D network for regenerating the bone for critical defects. The synthetic bone scaffolds can be classified into three broad categories. This classification primarily depends on the fracture sites, as illustrated in Fig. 1.2. Of late, 3D printing has emerged as an efficient solution to the fabrication of scaffolds for BTE, as it allows custom-designed scaffolds suitable to the defect. Various fabrication techniques allow superior control of parameters, such as pore size, porosity, surface roughness, and mechanical properties of the scaffolds to better suit the anatomy of the patient's defective bone. Synthetic bone grafts manufactured by AM technologies can also be integrated with active biomolecules. They can influence bone growth by acting on the antagonist of bone marker genes and enhancing its proliferation. Most synthetic grafts are natural bone matrix (ECM) or βTCP scaffolds infused with bioactive molecules. Some of these products include rh-BMP-2 [Infuse® bone graft] (Ho-Shui-Ling et al., 2018), rh-BMP-7 [Osigraft] (Ho-Shui-Ling et al., 2018), rh-PDGF [Augment® bone graft] (Krell et al., 2016), rhBMP-6 + whole blood coagulum [Osteogrow] (Genera Research Ltd, 2014), and allograft-derived growth factor [Osteoamp] (Ho-Shui-Ling et al., 2018). These bone grafts are mainly used for cervical and lumbar spine, wrist, ankle, and grim fractures of femur and tibia, where the fracture size is between 2 to 4 cm. The last category of scaffolds relies on the delivery of cells encapsulated on cell-based scaffolds (Bolander et al., 2017). The commonly used stem cells are PDSCs, BMSCs, and ASCs. The "as-prepared" construct can be further nourished and developed in a bioreactor system to reach a more advanced stage (Ho-Shui-Ling et al., 2018), in which a 3D network is established that stimulates the entrapped stem cells to develop into new tissue or heal the defect site (Ingber et al., 2006). Stem cell therapies, combined with an allogenic graft matrix or HAP matrix usually heal critical size defects greater than 4 cm by