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Investigating the Influence of Architecture and Material Composition of 3D Printed Anatomical Design Scaffolds for Large Bone Defects
and ceramic content. For the same architecture, the decreasing the PS, suggesting that the gradient structure
compressive modulus increases by increasing the is able to induce cell growth in a gradient manner (cross-
ceramic content, and for the same level of reinforcement, section images, clearly indicate the effect of cell density
the compressive modulus is higher in bone bricks as a function of PS) (Figure 7B, D, F, H). Results also
containing TCP than HA. For bone bricks with the same show that cell bridging mainly occurs in the crossing
material composition and the same number of double sections of adjacent layers and filaments with smaller PS.
layers, compressive modulus increases by increasing the Cells are also attaching and proliferating but with reduced
number of spiral filaments. Similarly, for bone bricks kinetics on scaffolds presenting different architectures, as
with the same material composition and the same number shown in Figure 8.
of spiral filaments, compressive modulus increases by
increasing the number of double filaments. This can be 4. Conclusion
explained by the overall decrease in porosity. Results
also show that by controlling the number of double This paper investigates the effects of bone bricks
and spiral filaments, it is possible to create bone bricks architecture (PS gradient) and material composition
with compressive modulus in the trabecular region and (reinforcement and chemical cues) on the morphological,
presenting much higher values than previously reported mechanical, and biological properties of printed bone bricks
for standard regular square scaffolds . For rectangular designed according to anthropometric data. Bone bricks
[28]
shape scaffolds with PS around 300 μm, results show an with complex architectures mimicking the patient bone
increase of compressive modulus from 48 MPa to 75 MP structure were successfully produced using a screw-assisted
(PCL scaffolds containing 20 wt% of HA) and 88 MPa extrusion-based additive manufacturing system. For
(PCL scaffolds containing 20 wt% of TCP) . However, different architectures were printed, changing the number
[28]
produced bone bricks present significantly high of double and spiral filaments which also allowed to control
compressing modulus (the maximum achieved value the overall porosity. Results show that by controlling both
was 334.9 MPa), enabling their use for load-bearing the architecture and material composition, it is possible
applications such as for trabecular bone applications to control the mechanical and biological performance of
(compressive modulus ranging from 50 to 1500 MPa the bone bricks. Table 2 summarizes the obtained results,
with the mean value of 194 MPa) [29]-[32] . identifying the optimal architecture regarding mechanical
and biological behavior. For the same architecture, high
3.3. Biological analysis mechanical properties were obtained with TCP bone bricks
(344.9 MPa), while high cell metabolic activity suggesting
Figure 6 shows the fluorescence intensity versus high cell attachment and proliferation was obtained with
material composition for the four bone bricks
architectures at different time points (days 1, 7, and HA bone bricks (11216 AU). Considering both mechanical
14) after cell seeding. High fluorescence intensity properties and biological results, case 4 produced with
values correspond to high cell metabolic activity. PCL/TCP seems to be the ideal configuration.
Results suggest that printed bone bricks do not present Conflict of interest
any cytotoxicity being able to support cell attachment
and proliferation. For all architectures and material All authors declare that they have no conflicts of
composition, cell metabolic activity increases from interest.
day 1 to day 7, suggesting cell proliferation. For the
same architecture and level of ceramic reinforcement, Acknowledgments
cell metabolic activity is higher in the HA bone bricks
than TCP bone bricks. Statistical high values were This project has been supported by the University of
obtained for bone bricks containing high levels of HA Manchester and the EPSRC of the UK, the GCRF, grant
(20 wt%) and configuration 3. Fluorescence intensity number EP/R01513/1.
also increases from case 1 (large PS) to case 4 (low PS)
as in case 1, cell bridging between filaments is more References
difficult. Moreover, for the same material composition,
case 3 presents high cell metabolic activity than case 1. Dilogo I, Primaputra M, Pawitan J, et al., 2017, Modified
4, which can be explained by the high surface area Masquelet Technique Using Allogeneic Umbilical Cord-
which promotes cell attachment. derived Mesenchymal Stem Cells for Infected Non-union
Figure 7 shows SEM images of bone bricks (case 3)
seeded with cells at day 14. Results show that cells are Femoral Shaft Fracture with a 12 cm Bone Defect: A Case
spread over the bone bricks (Figure 7A, C, E, G). It is Report. Int J Surg Case Rep, 34:11–6.
also possible to observe that cell intensity increases by https://doi.org/10.1016/j.ijscr.2017.03.002.

50 International Journal of Bioprinting (2021)–Volume 7, Issue 2