A novel decellularized matrix of Wnt signaling-activated osteocytes accelerates the repair of critical-sized parietal bone defects with osteoclastogenesis, angiogenesis, and neurogenesis
dc.contributor.author | Wang, Xiaofang | |
dc.contributor.author | Ma, Yufei | |
dc.contributor.author | Chen, Jie | |
dc.contributor.author | Liu, Yujiao | |
dc.contributor.author | Liu, Guangliang | |
dc.contributor.author | Wang, Pengtao | |
dc.contributor.author | Wang, Bo | |
dc.contributor.author | Taketo, Makoto M. | |
dc.contributor.author | Bellido, Teresita | |
dc.contributor.author | Tu, Xiaolin | |
dc.contributor.department | Anatomy, Cell Biology and Physiology, School of Medicine | |
dc.date.accessioned | 2023-08-25T11:52:43Z | |
dc.date.available | 2023-08-25T11:52:43Z | |
dc.date.issued | 2022-08-16 | |
dc.description.abstract | Cell source is the key to decellularized matrix (DM) strategy. This study compared 3 cell types, osteocytes with/without dominant active Wnt/β-catenin signaling (daCO and WTO) and bone marrow stromal cells (BMSCs) for their DMs in bone repair. Decellularization removes all organelles and >95% DNA, and retained >74% collagen and >71% GAG, maintains the integrity of cell basement membrane with dense boundaries showing oval and honeycomb structure in osteocytic DM and smooth but irregular shape in the BMSC-DM. DM produced higher cell survival rate (90%) and higher proliferative activity. In vitro, daCO-DM induces more and longer stress fibers in BMSCs, conducive to cell adhesion, spreading, and osteogenic differentiation. 8-wk after implantation of the critical-sized parietal bone defect model, daCO-DM formed tight structures, composed of a large number of densely-arranged type-I collagen under polarized light microscope, which is similar to and integrated with host bone. BV/TV (>54%) was 1.5, 2.9, and 3.5 times of WTO-DM, BMSC-DM, and none-DM groups, and N.Ob/T.Ar (3.2 × 102/mm2) was 1.7, 2.9, and 3.3 times. At 4-wk, daCO-DM induced osteoclastogenesis, 2.3 times higher than WTO-DM; but BMSC-DM or none-DM didn't. daCO-DM increased the expression of RANKL and MCSF, Vegfa and Angpt1, and Ngf in BMSCs, which contributes to osteoclastogenesis, angiogenesis, and neurogenesis, respectively. daCO-DM promoted H-type vessel formation and nerve markers β3-tubulin and NeuN expression. Conclusion: daCO-DM produces metabolic and neurovascularized organoid bone to accelerate the repair of bone defects. These features are expected to achieve the effect of autologous bone transplantation, suitable for transformation application. | |
dc.eprint.version | Final published version | |
dc.identifier.citation | Wang X, Ma Y, Chen J, et al. A novel decellularized matrix of Wnt signaling-activated osteocytes accelerates the repair of critical-sized parietal bone defects with osteoclastogenesis, angiogenesis, and neurogenesis. Bioact Mater. 2022;21:110-128. Published 2022 Aug 16. doi:10.1016/j.bioactmat.2022.07.017 | |
dc.identifier.uri | https://hdl.handle.net/1805/35125 | |
dc.language.iso | en_US | |
dc.publisher | Elsevier | |
dc.relation.isversionof | 10.1016/j.bioactmat.2022.07.017 | |
dc.relation.journal | Bioactive Materials | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | en |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.source | PMC | |
dc.subject | 3D printing | |
dc.subject | Decellularized matrix | |
dc.subject | Metabolic and neurovascular organoid bone | |
dc.subject | Osteocyte | |
dc.subject | Regenerative repair | |
dc.subject | Wnt signaling | |
dc.title | A novel decellularized matrix of Wnt signaling-activated osteocytes accelerates the repair of critical-sized parietal bone defects with osteoclastogenesis, angiogenesis, and neurogenesis | |
dc.type | Article |