Treating critical-size bone defects with autografts,
allografts,
or standardized implants is challenging since the healing of the defect
area necessitates patient-specific grafts with mechanically and physiologically
relevant structures. Three-dimensional (3D) printing using computer-aided
design (CAD) is a promising approach for bone tissue engineering applications
by producing constructs with customized designs and biomechanical
compositions. In this study, we propose 3D printing of personalized
and implantable hybrid active scaffolds with a unique architecture
and biomaterial composition for critical-size bone defects. The proposed
3D hybrid construct was designed to have a gradient cell-laden poly(ethylene
glycol) (PEG) hydrogel, which was surrounded by a porous polycaprolactone
(PCL) cage structure to recapitulate the anatomical structure of the
defective area. The optimized PCL cage design not only provides improved
mechanical properties but also allows the diffusion of nutrients and
medium through the scaffold. Three different designs including zigzag,
zigzag/spiral, and zigzag/spiral with shifting the zigzag layers were
evaluated to find an optimal architecture from a mechanical point
of view and permeability that can provide the necessary mechanical
strength and oxygen/nutrient diffusion, respectively. Mechanical properties
were investigated experimentally and analytically using finite element
analysis (FEA), and computational fluid dynamics (CFD) simulation
was used to determine the permeability of the structures. A hybrid
scaffold was fabricated via 3D printing of the PCL cage structure
and a PEG-based bioink comprising a varying number of human bone marrow
mesenchymal stem cells (hBMSCs). The gradient bioink was deposited
inside the PCL cage through a microcapillary extrusion to generate
a mineralized gradient structure. The zigzag/spiral design for the
PCL cage was found to be mechanically strong with sufficient and optimum
nutrient/gas axial and radial diffusion while the PEG-based hydrogel
provided a biocompatible environment for hBMSC viability, differentiation,
and mineralization. This study promises the production of personalized
constructs for critical-size bone defects by printing different biomaterials
and gradient cells with a hybrid design depending on the need for
a donor site for implantation.