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International Journal of Bioprinting Osteocytic Wnt7b-PKCδ against microgravity

(~500 μm diameter), facilitating excellent nutrient/ Funding
metabolite transport, and closely mimicking the in vivo This work was supported by the National Natural Science
physiological conditions. The RCCS rotation provides Foundation of China (grant numbers: 82471909, 81672118,
23
TM
simulated microgravity while ensuring sufficient mass and 32101053) and the Chongqing Natural Science
transport for 3D tissue culture. Using this advanced Foundation (grant numbers: CSTB2022NSCQ-LZX0048
59
system, we confirmed that osteocytic Wnt7b robustly and CSTB2023NSCQ-MSX0424).
promotes osteogenic differentiation of stromal cells
under microgravity, consistent with our in vivo finding of Conflict of interest
increased lumbar BMD in protected mice.
The authors declare they have no competing interests.
Furthermore, advances in BTE and 3D printing enable
precise control over implant shape and structure. 61,62 Author contributions
Integrating bioactive microenvironments with printing
materials is key to enhancing implant functionality. 63,64 Conceptualization: Xing Liu, Xiaolin Tu
Bioprinting combined with specific cellular Formal analysis: Jinling Zhang, Pengtao Wang, Xiaoling
microenvironments offers a powerful strategy for creating Chen, Yangxi Liu, Bo He
“smart” constructs that mimic the microenvironment Investigation: Jinling Zhang, Pengtao Wang, Xiaoling
to support stem cell proliferation, migration, and Chen, Saima Khan, Haiping Ouyang
differentiation. Our approach of co-printing Wnt7b- Methodology: Jinling Zhang, Pengtao Wang
65
expressing osteocytes with stromal cells within a PCL- Writing–original draft: Jinling Zhang, Pengtao Wang,
GelMA scaffold not only ensured excellent cell survival Xing Liu
and proliferation but also effectively supported osteogenic Writing–review & editing: Jinling Zhang, Pengtao Wang,
differentiation and mineralization. This underscores the Xian Li, Xing Liu, Xiaolin Tu
significant potential of osteocytic Wnt7b as a molecular
target and bioactive component for: (i) reconstructing Ethics approval and consent to participate
bone integrity in astronauts, long-term bedridden patients, All animal procedures were approved by the Institutional
or those with paralysis to prevent disuse osteoporosis; and Animal Care and Use Committee of Chongqing Medical
(ii) serving as a novel bioactive material for repairing University (IACUC-CQMU-2024-0277).
critical-sized bone defects.
Consent for publication
5. Conclusion
Not applicable.
In this study, we demonstrated that osteoblast-derived
Wnt7b effectively counteracted microgravity-induced Availability of data
bone loss by activating the sclerostin-independent PKCδ
pathway, which promotes osteogenesis while inhibiting Data presented in this study are available upon request
adipogenesis in bone marrow stromal cells. Through from the corresponding authors.
innovative 3D bioprinting technology, we developed a Further disclosure
functionalized osteocyte niche (PCI3D) and validated its
efficacy in a simulated microgravity system (3D-BWBM), This study was presented orally by Jinling Zhang at the
confirming that Wnt7b exerts a protective effect 2023 China Biomaterials Conference in October 2023.
towards weightlessness-induced bone loss. Our findings
highlight Wnt7b-PKCδ signaling as a novel target for References
the treatment of disuse osteoporosis and establish a
scalable bioengineering strategy for bone regeneration in 1. McCarthy ID. Fluid shifts due to microgravity and their
extreme environments. Future in vivo studies will further effects on bone: a review of current knowledge. Ann Biomed
elucidate its translational potential in spaceflight and Eng. 2005;33:95-103.
doi: 10.1007/s10439-005-8967-6
clinical applications.
2. Lang T, LeBlanc A, Evans H, Lu Y, Genant H, Yu A. Cortical
Acknowledgments and trabecular bone mineral loss from the spine and hip
in long-duration spaceflight. J Bone Miner Res. 2004;19:
The authors are grateful to Lynda Bonewald for kindly 1006-1012.
providing the MLO-Y4 cell line. doi: 10.1359/jbmr.040307

Volume 11 Issue 4 (2025) 442 doi: 10.36922/IJB025240238