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

作者全名:"Wang, Xiaofang; Ma, Yufei; Chen, Jie; Liu, Yujiao; Liu, Guangliang; Wang, Pengtao; Wang, Bo; Taketo, Makoto M.; Bellido, Teresita; Tu, Xiaolin"

作者地址:"[Wang, Xiaofang; Ma, Yufei; Chen, Jie; Liu, Yujiao; Liu, Guangliang; Wang, Pengtao; Wang, Bo; Tu, Xiaolin] Chongqing Med Univ, Inst Life Sci, Lab Skeletal Dev & Regenerat, Chongqing 400016, Peoples R China; [Taketo, Makoto M.] Kyoto Univ, Grad Sch Med, Dept Pharmacol, Kyoto 6068501, Japan; [Bellido, Teresita] Univ Arkansas Med Sci, Dept Physiol & Cell Biol, Little Rock, AR 72223 USA; [Tu, Xiaolin] Indiana Univ Sch Med, Dept Anat & Cell Biol, Indianapolis, IN 46202 USA"

通信作者:"Tu, XL (通讯作者),Chongqing Med Univ, Inst Life Sci, Lab Skeletal Dev & Regenerat, Chongqing 400016, Peoples R China."

来源:BIOACTIVE MATERIALS

ESI学科分类: 

WOS号:WOS:000844689900001

JCR分区:Q1

影响因子:18.9

年份:2023

卷号:21

期号: 

开始页:110

结束页:128

文献类型:Article

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

摘要:"Cell source is the key to decellularized matrix (DM) strategy. This study compared 3 cell types, osteocytes with/ without dominant active Wnt/beta-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 x 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 markers beta 3-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."

基金机构:"National Natural Science Foundation of China [U1601220, 81672118, 82072450, 82002310]; Chongqing Science and Technology Commission-Basic Science and Frontier Technology Key Project [cstc2015jcyjBX0119]; CQMU Program for Youth Innovation in Future Medicine [W0075]"

基金资助正文:"This research was funded by the 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.) , and CQMU Program for Youth Innovation in Future Medicine, W0075 (Y.M.) ."