Page 58 - Development of Functional Scaffolds for Bone Tissue Engineering Using 3D-Bioprinting of Cells and Biomaterials - Yasaman Zamani

INTRODUCTION
Mandibular bone defects can result from injury due to facial trauma, infection, tumor resection, or flawed developmental processes. Current treatment for these defects comprises autologous bone graft (autograft) or microvascular free flaps [1]. However, autografts are associated with several disadvantages such as limited supply, need for multiple surgeries, and donor side morbidity [2]. In an attempt to overcome these limitations, tissue engineering, i.e. the design and fabrication of tissue equivalents for restoration of diseased or lost tissues, has emerged since the 1980s [3]. In bone tissue engineering, the scaffold used plays a critical role in the formation of the new bone. The scaffold should have certain properties, i.e. it should be biocompatible, osteoconductive, osteoinductive, biodegradable with a degradation rate proportional to new bone formation, and its mechanical properties should match the mechanical properties of the surrounding bone [4].
Poly(ɛ-caprolactone) (PCL) is a biodegradable polymer in the family of poly(α-hydroxy esters) that has already been approved by the US Food and Drug Administration [5]. It is the most widely used polymer for 3D-printing of scaffolds, since it has low melting temperature (58 – 65°C) and low glass transition temperature (-60 – -65°C), which makes it easy to process in contrast to other polyesters such as poly-L-lactic acid (PLLA, melting point: 170 – 200°C, glass transition temperature: 55 – 65°C ) and polyglycolic acid (PGA, melting point: 220 – 233°C, glass transition temperature: 35 – 45°C) [6-8]. 3D-printing is a promising technology for fabrication of scaffolds with defined internal strusture and various geometries. Large mandibular and maxillary PCL bone scaffolds have been 3D-printed that replicate fine details extracted from patient’s computed tomography scans [9]. PCL scaffolds have also been used in combination with calcium phosphates such as hydroxyapatite and tri-calcium phosphate to improve their mechanical properties as well as to induce osteogenic differentiation of cells [10-12].
The mechanical strength of a bone tissue engineering scaffold is highly important. If the strength of the scaffold is less than that of the surrounding bone, the scaffold will probably fail before it is replaced by ingrowing bone. On the other hand, if the mechanical strength of the scaffold is higher than that of the surrounding bone, stress shielding will occur [13]. Stress shielding prevents the bone from being exposed to normal levels of mechanical loading. This leads to bone resorption and lack of bone ingrowth into the scaffold [13,14]. Mechanical properties of scaffolds can be controlled by the scaffold material as well as scaffold micro-structure. Customized mandibular shaped scaffolds from acrylic resin and glass fiber reinforced composites have been 3D-printed with stiffness close to human mandible [15]. Mechanical and microstructural
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