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International Journal of Bioprinting 3D-printed bioceramic scaffolds for bone regeneration
LS-graft, the L-graft formed a larger quantity of bone and mechanism by which this system can be made simpler.
demonstrated higher mechanical strength than the LS- However, the simple two-dimensional cell culture was
graft. These findings demonstrate that porosity can be quite different from the dynamic and complex system of
reduced without sacrificing bone formation by controlling segmental bone defects in this study, and it seems inefficient
the pore structure based on the bone defect morphology, for elucidating the mechanism of pore orientation effects.
thereby avoiding a reduction in graft strength. Moreover, Although the 3D dynamic culture of several types of cells
we found that the L-graft formed a bone oriented in the may mimic segmental bone defects and be effective for the
direction of the bone axis, whereas the LS-graft formed elucidation of the mechanism, the establishment of a 3D
bone that was not oriented in an orderly fashion, resulting culture system requires considerable time and effort, and
in obstruction of the bone marrow. Thus, the formation that alone is one research project. We intend to elucidate
of oriented bone and the avoidance of bone marrow this mechanism in future studies.
obstruction are other benefits of pore structure control Longer-term observations may reveal more pronounced
based on the consideration of bone defect morphology.
effects of the graft pore structure on bone regeneration
In clinical practice, grafts should be used differently, because obstruction of the bone marrow is the beginning
depending on the site and morphology of the bone defect. of non-union. Therefore, we plan to conduct long-term
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When bone should be formed along one axis, for example, animal experiments in future.
bone reconstruction in segmental bone defects as in this
study and vertical bone augmentation in dentistry, grafts 4. Conclusion
with a uniaxial porous structure, such as a honeycomb and CAp grafts with uniaxial pores parallel, perpendicular,
tube, including the L-graft, are considered suitable. 21-24,27,37,40 or both parallel and perpendicular to the bone axis were
In bone defects where surrounding bone is present, 3D fabricated. The pores of these grafts opened onto the bone
porous grafts and grafts with biaxial pores, such as the stumps, muscles, and both bone stumps and muscles. These
LS-graft, may be useful. 41,42 However, despite this type of grafts were implanted into segmental bone defects of rabbit
bone defect, when the host bone is oriented, grafts with ulnae to evaluate the effects of pore architecture on bone
a uniaxial porous structure seem more suitable than 3D ingrowth and orientation. In CAp grafts with uniaxial pores
porous grafts for regenerating bone along the bone axis.
perpendicular and both parallel and perpendicular to the
In future studies, optimization of the pore size and shape bone axis, fibrous tissue invaded the pores faster than the
is required because previous studies have demonstrated new bone, preventing bone formation and resulting in
that these characteristics affect tissue invasion and bone disordered bone ingrowth orientation. In contrast, in CAp
formation. 43,44 Zhao et al. reported that calcium phosphate grafts with uniaxial pores parallel to the bone axis, the pores
cement graft with 200–300 µm pores promoted bone preferentially allow the invasion of new bone. Consequently,
formation compared to those with 300–450 µm and 450– the bone oriented along the direction of the bone axis was
600 µm pores in radius segmental bone defects in rabbits. abundantly formed. The findings of this study provide an
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Van Bael et al. reported the effects of pore size (500 and understanding of the effect of graft pore structure on the
1000 µm) and pore shape (triangular, hexagonal, and amount and orientation of formed bone and contribute to
rectangular) on the in vitro proliferation and differentiation the development of grafts with optimal pore structures for
of 3D human periosteum-derived cell cultures using the reconstruction of segmental bone defects.
Ti6Al4V bone grafts. They reported that the smaller pore
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(500 μm) was more beneficial for cell growth than larger Acknowledgments
pores (1000 µm), and the triangular pore exhibited higher None.
alkaline phosphatase activity of cells than hexagonal and
rectangular pores. In this study, the graft possessed square Funding
pores of ~500 µm on a side; however, changing the pores
to 200–300-µm pores in triangular shape may improve the This study was supported in part by Japan Agency for
bone formation. Medical Research and Development under grant no.
JP22ym0126098h and Japan Society for the Promotion
This study showed that soft tissues occupied the graft
when the pores were oriented toward the soft tissues, of Science KAKENHI under grant nos. JP23K18593
whereas bone was preferentially formed in the graft when and JP22H03954.
the pores were oriented only toward the bone. However,
this study did not elucidate the underlying mechanism Conflict of interest
in detail. In vitro studies are useful for elucidating the The authors declare no conflicts of interest.
Volume 10 Issue 2 (2024) 454 doi: 10.36922/ijb.2323

