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International Journal of Bioprinting 3D printing in bone regeneration and bone repair

need to be solved: (1) as natural bone contains cortical the omission of a large body of relevant studies published
and cancellous multiscale hierarchical structures, 3DP is in other languages, particularly considering China’s high
expected to precisely reconstruct complex microstructures; contribution of publications in the area. Moreover, it was
as mentioned before, the DLP method combined with entirely up to an experienced expert to make the final
finite element analysis can produce highly interconnected decision when disagreements occurred during the data
pore architectures; advanced printing technology should selection process. Last, recently published articles that
be designed in such a way to allow for significantly higher were not in press during the search period were excluded,
solution concentrations without clogging the nozzle; and the citation data for high-impact publications that
(2) novel 3DP materials should be created with specific appeared recently might not have reflected their true
properties, such as good cell biocompatibility, controlled impact, which could lead to some prediction bias when
biodegradability, superior mechanical properties, and analyzing time-dependent trends and keywords based on
excellent vascularization and osteogenic differentiation; the included publications.
however, most of the present materials fail to meet
the aforementioned properties, thus hindering their 5. Conclusion
applications in clinical practice; (3) multidisciplinary Our study presents the first comprehensive bibliometric
therapeutic strategies for bone regeneration and bone and visualized analysis of 3DP in bone repair and
repair should be developed as well; as defects might result regeneration, reflecting research trends in the field over
from significant traumatic injuries, bone tumors, and bone the last 10 years. This study systematically shows the
infection, printed scaffolds should not only have the capacity global trends in this rapidly evolving area and may assist
for bone reconstruction, but also target the treatment researchers in identifying influential authors, institutions,
of specific bone diseases with antibacterial and tumor and journals. Moreover, the keyword and co-citation
cell eradication abilities; (4) the molecular and cellular clustering analyses enable researchers to identify research
mechanisms underlying bone repair remain unclear; the directions mainly in four categories: “3DP techniques,”
development of 3DP for BTE is governed by a detailed “3DP materials,” “bone regeneration strategies,” and “bone
knowledge of these regenerative mechanisms; the process disease therapeutics.” Gaining an in-depth understanding
of bone regeneration can be divided into four overlapping of current studies in this growing field of research will
stages, which are hemostasis, inflammation, repair, and be beneficial for researchers to further contribute to the
remodeling ; one of the important stages is dependent advancement of knowledge and push the frontiers of 3DP
[54]
on the regulatory role of immune cells, particularly in bone repair and regeneration from preclinical studies to
macrophages, with the M1 phenotype producing pro- clinical implementation.
inflammatory cytokines and the M2 phenotype producing
anti-inflammatory effects; it is widely accepted that the M2 Acknowledgments
phenotype is permissive to bone regeneration and repair,
but excessive infiltration of M2 macrophages might not None.
be conducive to bone regeneration; instead, it may impair
tissue healing; therefore, an in-depth exploration of the Funding
underlying mechanisms would additionally enable 3DP This study was supported by National Natural Science
development to be effectively harnessed to improve bone Foundation of China (82102552), and Beijing Natural
regeneration. Science Foundation (7212118, L222087).

4.4. Study strengths and limitations Conflict of interest
Our study provided a comprehensive bibliometric and
visualized analysis of current literature reporting 3DP in The authors declare no conflicts of interest.
bone repair and regeneration. Some limitations should be Author contributions
considered when interpreting the results of our study. First,
literature searches using PubMed, Cochrane, Scopus, and Conceptualization: Weimin Guo, Licheng Zhang, Jianhao
Embase library databases were not performed, as all studies Lin
were collected from the WoSCC. Although the WoSCC Formal analysis: Zihao He, Hui Li, Hao Li
is considered a comprehensive database that captures Methodology: Jianjing Lin, Zhen Yang
all available literature in the field, study retrieval from a Visualization: Dan Xing, Hao Li
single database could nevertheless result in selection bias. Writing – original draft: Zhen Yang, Hao Li
Second, non-English language articles and nonresearch/ Writing – review & editing: Jiao Jiao Li, Elise M. Cribbin,
review articles were not included in this study, resulting in Alice M. Kim

Volume 9 Issue 4 (2023) 330 https://doi.org/10.18063/ijb.737