Page 130 - Development of Functional Scaffolds for Bone Tissue Engineering Using 3D-Bioprinting of Cells and Biomaterials - Yasaman Zamani

GENERAL SUMMARY
Large bone defects occur as a consequence of traumatic injuries and pathological conditions, and their reconstruction still remains challenging. Autografts are considered the standard procedure for the treatment of large bone defects; however their use is limited by donor availability, donor site morbidity, and need for multiple surgeries. Bone tissue engineering is rapidly developing as an alternative for the use of autografts in the treatment of large bone defects. Scaffolds play a critical role in the formation of new bone in the defect site. Conventional methods for the fabrication of tissue engineering scaffolds such as freeze drying and solvent casting-porogen leaching, have limitations such as toxic solvent residues, inaccurate control of the internal structure, and poor ability to customize for specific defect sites. 3D-printing is a relatively new technology used for the fabrication of various tissue engineering scaffolds with controlled shape and internal structure. Polycaprolactone (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. Due to the intrinsic hydrophobicity and surface smoothness, 3D-printed PCL scaffolds need surface modification for improved cell attachment, proliferation, and differentiation. Surface chemical modification by sodium hydroxide (NaOH) and immobilization of RGD on the surface of PCL scaffolds are among the most common approaches used for the improvement of PCL surface properties. In Chapter 2, the osteogenic activity of MC3T3-E1 pre-osteoblasts on chemically surface-modified or RGD immobilized 3D-printed PCL scaffolds was studied. We showed that RGD immobilization (0.011 μg/mg scaffold) on the surface and 24 h NaOH treatment of the surface of 3D-printed PCL scaffolds both enhance pre-osteoblast proliferation and matrix deposition, while only 24 h NaOH treatment results in increased osteogenic activity, making it the treatment of choice to promote bone formation by osteogenic cells.
Mechanical properties of bone tissue engineering scaffolds play a major role in their in vivo performance. Natural bones are not exposed to homogeneous stresses during normal functions and therefore, prediction of forces induced to the native bone during normal functioning is important in the design, fabrication, and integration of scaffolds with the host. In Chapter 3, we predicted the forces and torques induced on the mandibular symphysis during jaw opening and closing by finite element modeling to customize the mechanical properties of 3D-printed PCL scaffolds accordingly. Our modeling results showed that during jaw opening, the highest force induced to the symphyseal line is a transverse compressive force that reduces from top-to-bottom, while a small tensile force is induced only to the lower parts of the symphysis. Therefore, we designed gradient scaffolds with increasing void size from top-to-bottom to achieve gradient
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