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International Journal of Bioprinting                               Osteoconduction and scaffold directionality



            pores were randomly distributed, directionality was   double-filament configurations, hollow, core–shell, and
            not addressed in that study. The directionality of   bionic filaments . How such new developments will
                                                                            [29]
            vascularization is largely hypoxia-driven (low tissue   influence  scaffold-based bone  tissue  engineering will be
            oxygen level), which promotes the sprouting of     seen over the next decade.
            endothelial cells toward the oxygen-deprived tissue [36,37] .
            For three different microarchitectures with pores from   5. Conclusions
            0.35 mm to 0.65 mm, blood vessel volume/total volume   In conclusion, we showed that for  filament-based
            increased with the pore diameter [38] . In our library, wall   microarchitectures, the directionality of filaments, which is a
            distances of 0.40 mm and 0.50 mm yielded the highest   guiding cue for osteoconduction, is a key factor for filament
            degree  of  osteoconduction  and  bone  regeneration   distance of 0.83 mm and beyond. At a distance of 0.40 mm
            irrespective of directionality of the filaments. One can   and 0.50 mm, directionality of filaments imposes no major
            assume that vascularization is no limiting factor for bone   influence on osteoconductivity. The optimal distance of
            regeneration in wide-open porous microarchitectures as   filaments to support and guide osteoconductivity is between
            tested in this study and even less so for rod distances   0.40 and 0.50 mm, given that multiple bone ingrowth fronts
            of 0.83 mm or 1.25 mm as realized in FilG083 and   will form in complex defect configurations.
            FilG125 scaffolds, where we saw a significant decline
            in bone formation compared to the smaller 0.40 mm   Acknowledgments
            and 0.50 mm filaments. That  suggests  that although
            vascularization is certainly a prerequisite for bone   The authors would like to thank Ana Perez for her
            formation and osteoconduction, it is not the limiting   assistance with histologies.
            factor in wide-open porous microarchitectures.
               The  optimal pore diameter for  osteoconduction  was   Funding
            found for TCP-based scaffolds to be between 0.70 and   This research was funded by the Swiss National Science
                                                        [13]
            1.20 mm with bottlenecks between 0.50 and 0.70 mm    Foundation, grant number: 310030_197128 to FEW
            and optimal rod distance in  orthogonal titanium lattice
                                       [39]
            microarchitectures to be 0.80 mm . Here, for TCP-based   Conflict of interest
            filament microarchitectures, optimal filament distance   The authors declare no conflicts of interest.
            for osteoconduction was between 0.40 and 0.83  mm for
            the Fil-type configuration and between 0.40 and 0.50   Author contributions
            mm for the FilG-type configuration. Irrespective of
            the microarchitecture type, it appears that voids in any   Conceptualization: Franz E. Weber
            microarchitecture should span not more than 0.80 mm   Methodology: Chafik Ghayor, Indranil Bhattacharya, Julien
            to ensure high osteoconductivity and optimal guiding   Guerrero, Franz E. Weber
            of bone ingrowth. The diagonal of 0.80 mm squares   Formal analysis: Chafik Ghayor, Indranil Bhattacharya,
            measures 1.13 mm and comes close to the maximal pore   Julien Guerrero, Franz E. Weber
            size of osteoconductive pore-based microarchitectures of   Investigation: Chafik Ghayor, Indranil Bhattacharya, Julien
            1.20 mm [1,13] . Despite the high variability of these diverse   Guerrero, Franz E. Weber
            microarchitectures, based on pores, lattice or filaments, the   Resources: Franz E. Weber
            optimal dimension of the voids between material surfaces is   Data curation: Chafik Ghayor, Indranil Bhattacharya,
            in a range between 0.80 mm and 1.20 mm. Therefore, these   Julien Guerrero, Franz E. Weber
            numbers can be applied to other microarchitectures as well.  Writing—original draft preparation: Franz E. Weber
                                                               Writing—review and editing: Chafik Ghayor, Indranil
               In this study, we used a grid-like configuration of
                                                                  Bhattacharya, Julien Guerrero, Franz E. Weber
            filament microarchitectures based on square-shaped   Visualization: Chafik Ghayor, Indranil Bhattacharya, Franz
            filaments. One could suspect that square-shaped filaments   E. Weber
            enhance directionality, since they expose directional strait   Supervision: Franz E. Weber
            surfaces to the ingrowing bone. To study the effect of round   Funding acquisition: Franz E. Weber
            versus square-shape filaments, additional studies on this
            subject are needed. Moreover, in this study, we only looked   Ethics approval and consent to participate
            at grid-like configurations but also other configuration
            with wavelike or honeycomb patterns can be produced with   The protocol was in line with the European Union
            extrusion-based 3D printing techniques. Such variations   Directive 2010/63/EU and accepted by the local authorities
            change the mechanics and the in vitro outcomes , as do   (065/2018).
                                                   [40]

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            Volume 9 Issue 1 (2023)olume 9 Issue 1 (2023)   69                      https://doi.org/10.18063/ijb.v9i1.626
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