Page 31 - Development of Functional Scaffolds for Bone Tissue Engineering Using 3D-Bioprinting of Cells and Biomaterials - Yasaman Zamani

INTRODUCTION
Large bone defects caused by trauma or tumor resection often cannot heal by the natural process of bone regeneration. The golden standard treatment for such defects is still considered autologous bone, i.e. bone harvested from the same patient at a different surgical site and transplanted to the defect site [1]. However, autografts are associated with several disadvantages such as limited supply, extended healing time, and need for multiple surgeries [2]. Bone tissue engineering is rapidly becoming a promising alternative, eliminating the need for additional surgeries. For bone tissue engineering, a scaffold is required to temporarily substitute the extracellular matrix. Traditionally, bone tissue engineering scaffolds have been fabricated using techniques such as freeze drying, solvent casting-porogen leaching, and gas foaming. However, with these techniques one cannot control the porosity, internal architecture, and geometry of the scaffold [3]. Currently, three-dimensional (3D) printing technology is extensively used for the fabrication of various tissue engineering scaffolds with controlled shape and internal structure [4,5].
The most commonly used polymers to fabricate scaffolds for bone tissue engineering are poly(α-hydroxy esters), such as poly(ɛ-caprolactone) (PCL), polylactic acid (PLA), and poly(lactic- co-glycolic) acid (PLGA). The major advantage of these polymers is their tailorable degradation rate and that their degradation products are removed by natural pathways without adverse effects [6]. These polymers also have excellent mechanical properties suitable for bone replacement, and have already been approved by the US Food and Drug Administration [7]. PCL is the most widely used polymer for 3D-printing of bone scaffolds, since it has low melting and glass transition temperatures which makes it easy to process [8,9]. However, PCL is hydrophobic in nature and lacks biological recognition sites, and therefore needs surface modification for enhanced cellular attachment, proliferation, and differentiation [10-12]. Moreover, when PCL is 3D-printed, the produced strands are smooth and contain no features or cues for cell attachment [13,14]. Therefore, a surface modification step prior to cell seeding is required to overcome these obstacles.
There are numerous surface modification methods including physical (e.g. ɣ-radiation, plasma treatment), chemical (e.g. hydrolysis, aminolysis) or biological methods (e.g. coating, immobilization of biologically active molecules such as proteins and/or ligands on the surface). Hydrolysis of PCL by sodium hydroxide (NaOH) has been extensively used to increase PCL hydrophilicity by creation of carboxyl and hydroxyl groups [15-18]. Immobilization of RGD peptide (R: arginine; G: glycine; D: aspartic acid) on the surface of PCL has also been used to facilitate
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