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A novel decellularized matrix of Wnt signaling-activated osteocytes accelerates the repair of critical-sized parietal bone defects with osteoclastogenesis, angiogenesis, and neurogenesis

引用

Bioactive Materials 2023年第3期21卷 110-128页

作者： Xiaofang Wang Yufei Ma Jie Chen Yujiao Liu Guangliang Liu Pengtao Wang Bo Wang Makoto M.Taketo Teresita Bellido Xiaolin Tu Laboratory of Skeletal Development and Regeneration Institute of Life SciencesChongqing Medical UniversityChongqing400016China Department of Pharmacology Graduate School of MedicineKyoto UniversityKyoto606-8501Japan Department of Physiology and Cell Biology University of Arkansas for Medical SciencesLittle RockAR72223USA Department of Anatomy and Cell Biology Indiana University School of MedicineIndianapolisIN46202USA

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(3.2×10^(2)/mm^(2))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 markersβ3-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.

关键词： Decellularized matrix Osteocyte Wnt signaling 3D printing regenerative repair Metabolic and neurovascular organoid bone

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