CRANIOFACIAL BONE - 3D Bioprinting and Nanotechnology in Tissue Engineering and Regenerative Medicine - page 216

calvarium, zygoma, and orbital rim—demonstrating the ability to reproduce highly complex anatomi-
cal shapes ( Figure 10 . 2 B). Of the two cement scaffolds, brushite was stronger but less porous than
monetite; however, the bending strengths of these scaffolds were still at least two orders of magnitude
below that of cortical bone, underscoring the limited mechanical properties of scaffolds fabricated us-
ing this method.
10.3.3 CASE STUDY 3: MELT EXTRUSION METHOD
In the final case study, Temple et al. ( Temple et al., 2014 ) created porous PCL scaffolds using ME.
Because ME-based printers print the entire cross-section of each layer, this method allows complete
control over the pore size and porosity. Consequently, the final anatomically shaped scaffolds had
consistent rectangular pores throughout. The authors printed defined void volumes that ranged from
20-80%, and selected 60% to match cell seeding studies indicating uniform cell distribution at this
void volume. With this setup, the authors were able to seed adipose-derived stem cells (ASCs) through-
out the scaffold and induce the formation of bone and vascular tissue, suggesting the potential of this
technique for future vascularized bone grafts. The authors were also able to print the human maxilla
and mandible geometries with high fidelity and accuracy at full scale despite the requirement for sup-
port structures, directly demonstrating the feasibility of using ME to produce craniofacial scaffolds that
could be combined with other TE components for bone regeneration ( Figure 10 . 2 C ).
10.4 NANOTECHNOLOGY IN CRANIOFACIAL GRAFT DESIGN
Inspired by the nanotopography of the native bone extracellular matrix (ECM), nanoscale technolo-
gies have impacted the engineering strategies of craniofacial bone. These include the production of
nanocomposites to mimic bone ECM composition, and scaffolds composed of nanofibers to better
recapitulate the aspects of the native structure. Nanocarriers of bioactive agents were also incorporated
in scaffolds to regulate cellular behavior.
10.4.1 NANOCOMPOSITES IN CRANIOFACIAL BONE REGENERATION
A nanocomposite is a material with at least two distinct components and at least one of these compo-
nents is in the nanometer scale. Natural bone ECM is essentially a nanocomposite material composed
of collagen fibers, hydroxyapatite (HAp) nanocrystals, and proteoglycans, having a high degree of
structural hierarchy starting from the nanoscale. Therefore, approaches have been developed in order
to mimic this nanoscale composite structure of bone ECM.
As collagen type I and HAp are the main components of the bone tissue, their composites have been
extensively studied as scaffold materials in the engineering of bone grafts ( Wahl and Czernuszka, 2006 ;
He et al., 2010 ; Kim et al., 2012 ). In these studies, collagen type I was blended with nano HAp (nHAp)
crystals and the resulting nanocomposites were shown to be effective in the regeneration of several
craniofacial defect models including immature beagle cranium (diameter: 2.5 cm) ( He et al., 2010 ),
rabbit calvaria (diameter: 8 mm) ( Kim et al., 2012 ), and rat infraorbital bone (diameter: 3 mm) ( Amaro
Martins and Goissis, 2000 ).