Page 107 - Development of Functional Scaffolds for Bone Tissue Engineering Using 3D-Bioprinting of Cells and Biomaterials - Yasaman Zamani

INTRODUCTION
Bone defects are among the most common injuries in the body due to aging population, metabolic diseases such as osteoporosis, infectious diseases, and cancer. Bone is known for its self-healing capacity; however, 5-10% of bone defects end in nonunion and/or incomplete healing [1]. Although autografts are considered the standard treatment for nonunions, they have certain limitations such as limited supply, need for multiple surgeries, and possibility of damage to the nerves [2]. Bone tissue engineering is a promising alternative, eliminating the need for additional surgeries and donor site morbidity. The aim of tissue engineering is to replace, maintain, or enhance the function of damaged or diseased tissues by a combination of scaffolds, cells, and biological molecules [3]. A porous scaffold is crucial to provide a microenvironment for cell activities. The most commonly used materials for fabrication of bone tissue engineering scaffolds are calcium phosphates such as hydroxyapatite and β-tricalcium phosphate (β-TCP), poly(α- hydroxy esters) such as poly(ɛ-caprolactone) (PCL), polylactic acid (PLA), and poly(lactic-co- glycolic) acid (PLGA), and their composites [4, 5]. The main advantage of these polymers is their tailorable degradation rate and the removal of their degradation products by natural processes without adverse effects [6]. These polymers also have suitable mechanical properties for bone replacement, and are approved by the US Food and Drug Administration [7]. PLGA is the most popular biodegradable polymer due to its outstanding advantages including suitable mechanical properties especially toughness, adjustability of degradation rate, and excellent processability [8]. However, PLGA itself lacks osteoinductivity [9]. Therefore, materials enhancing bone formation such as hydroxyapatite and β-TCP are extensively used as a composite with PLGA [10-12].
Bone tissue engineering scaffolds have traditionally been fabricated using techniques such as freeze drying, solvent casting-porogen leaching, and gas foaming. These fabrication methods have limitations such as toxic solvent residues, inaccurate control of internal structure, and poor ability to customize for specific defect sites [13]. Additive manufacturing (AM) is a relatively new technology in which the final structure is built by adding layers of material based on a computer aided-design (CAD) file. AM technologies have attracted the attention of many fields especially the medical industry. One of the medical applications of AM is fabrication of tissue engineering scaffolds. In this regard, techniques such as fused deposition modeling (FDM), selective laser sintering (SLS), powder-based and extrusion-based 3D-printing are used for fabrication of scaffolds with controlled internal structure and geometry according to the defect site, whereafter target cells are seeded on the scaffolds [14]. However, conventional cell seeding methods have limitations such as low seeding efficiency and inhomogeneous distribution of cells
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