3D printed pore morphology mediates bone marrow stem cell behaviors via RhoA/ROCK2 signaling pathway for accelerating bone regeneration  

作　　者：Qiji Lu Jingjing Diao Yingqu Wang Jianlang Feng Fansen Zeng Yan Yang Yudi Kuang Naru Zhao Yingjun Wang 

机构地区：[1]School of Materials Science and Engineering,South China University of Technology,Guangzhou,510641,PR China [2]National Engineering Research Center for Tissue Restoration and Reconstruction,South China University of Technology,Guangzhou,510006,PR China [3]NMPA Key Laboratory for Research and Evaluation of Innovative Biomaterials for Medical Devices.Guangzhou,510006,PR China [4]Medical Devices Research&Testing Center of SCUT,Guangzhou,510006,PR China [5]School of Biomedical Sciences and Engineering,South China University of Technology,Guangzhou International Campus,Guangzhou,511442,PR China [6]Guangdong Institute of Advanced Biomaterials and Medical Devices,Guangzhou,510535,PR China

出　　处：《Bioactive Materials》2023年第8期413-424,共12页生物活性材料（英文）

基　　金：support from the National key research and development plan(Grant No.2021YFB3800800);the National Natural Science Foundation of China(52172281);Natural Science Foundation of Guangdong Province(Grant No.2021A1515011741&No.2020A1515011354);the Science and Technology Program of Guangdong Province(Grant No.2019B010941002);the Science and Technology Program of Guangzhou(Grant No.202007020002&No.202206040001);the financial support from the National Natural Science Foundation of China(Grant No.52002132);China Postdoctoral Science Foundation(2019M662925);J.D.acknowledges the financial support from Guangzhou Science and Technology Planning Project(202102020005);National Natural Science Foundation of China(Grant No.32201089);Guangdong Science and Technology Planning Project(2022A1515010608).

摘　　要：Bone bionics and structural engineering have sparked a broad interest in optimizing artificial scaffolds for better bone regeneration.However,the mechanism behind scaffold pore morphology-regulated bone regeneration remains unclear,making the structure design of scaffolds for bone repair challenging.To address this issue,we have carefully assessed diverse cell behaviors of bone mesenchymal stem cells(BMSCs)on theβ-tricalcium phosphate(β-TCP)scaffolds with three representative pore morphologies(i.e.,cross column,diamond,and gyroid pore unit,respectively).Among the scaffolds,BMSCs on theβ-TCP scaffold with diamond pore unit(designated as D-scaffold)demonstrated enhanced cytoskeletal forces,elongated nucleus,faster cell mobility,and better osteogenic differentiation potential(for example,the alkaline phosphatase expression level in D-scaffold were 1.5-2 times higher than other groups).RNA-sequencing analysis and signaling pathway intervention revealed that Ras homolog gene family A(RhoA)/Rho-associated kinase-2(ROCK2)has in-depth participated in the pore morphology-mediated BMSCs behaviors,indicating an important role of mechanical signaling transduction in scaffold-cell interactions.Finally,femoral condyle defect repair results showed that D-scaffold could effectively promote endogenous bone regeneration,of which the osteogenesis rate was 1.2-1.8 times higher than the other groups.Overall,this work provides insights into pore morphology-mediated bone regeneration mechanisms for developing novel bioadaptive scaffold designs.

关 键 词：Bone mesenchymal stem cells 3D-printed scaffold Pore morphology Bone regeneration Structure-osteogenesis relationship 

分 类 号：R318[医药卫生—生物医学工程]