Page 22 - Development of Functional Scaffolds for Bone Tissue Engineering Using 3D-Bioprinting of Cells and Biomaterials - Yasaman Zamani

compounds including hydrogel-encapsulated cells. If cells are printed simultaneously with the scaffold material, this is referred to as “3D-bioprinting”. Hydrogels are 3D networks that have a high water content. Several hydrogels such as fibrin [13], agarose [14], alginate [15], and gelatin methacrylate (GelMA) [16] have been used for cell printing. Alginate is a biocompatible natural polysaccharide composed of guluronic and mannuronic acids [17]. Due to its biodegradability, low cost, and gelation under mild conditions, alginate has been frequently used for encapsulation of cells in the bioprinting of bone tissue engineering scaffolds [18-21]. However, it is important to realize that, despite numerous reports on bioprinting of cells using different hydrogels, the advantageous or destructive effects of cell encapsulation, and its effects on cellular functions remain largely unsolved questions.
Options for optimization of 3D printing of tissue engineering scaffolds
Mechanical properties
Mechanical properties of scaffolds play a major role in their in vivo performance, in particular in bone tissue engineering. Implanted bone scaffolds are typically exposed to locally different mechanical stresses including compression, tension, and shear [22]. Therefore, the mechanical strength throughout the scaffold should ideally match the local mechanical properties of its surrounding bone to maximize the regenerative potential of the scaffold. Ingrowth of bone into the scaffold leads to biological fixation of the scaffold in the defect site which in turn plays a critical role in the formation of new bone in the defect site [23]. A mismatch of the mechanical properties can result in scaffold failure [24]. A combination of finite element modeling for prediction of the forces on the defect site during normal functions, and 3D-printing for customized design and fabrication of scaffolds accordingly, can contribute to improved performance and integration of the scaffold with native tissue.
Scaffold architecture and cellular responses
The cellular microenvironment is directly determined by the scaffold internal architecture. Scaffold architecture can affect cell growth, signaling, and osteogenic differentiation [25]. Scaffold porosity modulates cell migration and infiltration within the scaffold, and determines the available surface area for cells to proliferate and to deposit new matrix [26]. Scaffolds fabricated by conventional methods such as solvent casting-porogen leaching have a random porous internal structure that resembles the structure of cancellous bone. In contrast, scaffolds fabricated by AM techniques such as 3D-printing have ordered internal structure consisting of struts of scaffold material, which provide a large surface area for cell attachment and activities. Therefore, scaffolds with different
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