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

作　　者：Xiaofang Wang Yufei Ma Jie Chen Yujiao Liu Guangliang Liu Pengtao Wang Bo Wang Makoto M.Taketo Teresita Bellido Xiaolin Tu 

机构地区：[1]Laboratory of Skeletal Development and Regeneration,Institute of Life Sciences,Chongqing Medical University,Chongqing,400016,China [2]Department of Pharmacology,Graduate School of Medicine,Kyoto University,Kyoto,606-8501,Japan [3]Department of Physiology and Cell Biology,University of Arkansas for Medical Sciences,Little Rock,AR,72223,USA [4]Department of Anatomy and Cell Biology,Indiana University School of Medicine,Indianapolis,IN,46202,USA

出　　处：《Bioactive Materials》2023年第3期110-128,共19页生物活性材料（英文）

基　　金：National Natural Science Foundation of China U1601220(X.T.),81672118(X.T.),82072450(X.T.),82002310(Y.M.);Chongqing Science and Technology Commission—Basic Science and Frontier Technology Key Project cstc2015jcyjBX0119(X.T.);CQMU Program for Youth Innovation in Future Medicine,W0075(Y.M.).

摘　　要：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 

分 类 号：R318[医药卫生—生物医学工程]