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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
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