A hierarchical bilayer architecture for complex tissue regeneration  

作　　者：Min Yu Dan Luo Jing Qiao Jiusi Guo Danqing He Shanshan Jin Lin Tang Yu Wang Xin Shi Jing Mao Shengjie Cui Yu Fu Zixin Li Dawei Liu Ting Zhang Chi Zhang Zhou Li Yongsheng Zhou Yan Liu 

机构地区：[1]Laboratory of Biomimetic Nanomaterials,Department of Orthodontics,Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Laboratory for Digital and Material Technology of Stomatology&Beijing Key Laboratory of Digital Stomatology&Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health&NMPA Key Laboratory for Dental Materials,Beijing,100081,China [2]Department of Prosthodontics,Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Laboratory for Digital and Material Technology of Stomatology&Beijing Key Laboratory of Digital Stomatology&Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health&NMPA Key Laboratory for Dental Materials,Beijing,100081,China [3]CAS Center for Excellence in Nanoscience,Beijing Key Laboratory of Micro-nano Energy and Sensor,Beijing Institute of Nanoenergy and Nanosystems,Chinese Academy of Sciences,Beijing,101400,China [4]Department of Periodontology,The First Clinical Division,Peking University School and Hospital of Stomatology,Beijing,100034,China [5]State Key Laboratory of Oral Diseases,National Clinical Research Center for Oral Diseases,West China Hospital of Stomatology,Sichuan University,Chengdu,610041,China [6]Center of Stomatology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,430030,China [7]Fourth Division,Peking University Hospital of Stomatology,Beijing,100025,China

出　　处：《Bioactive Materials》2022年第4期93-106,共14页生物活性材料（英文）

基　　金：supported by the National Natural Science Foundations of China No.81871492(Y.L.),No.51902344(D.L.)and No.61875015(Z.L.);Ten-Thousand Talents Program QNBJ2019-2(Y.L.);Key R&D Plan of Ningxia Hui Autonomous Region No.2020BCG01001(Y.L.);National Key R&D Project from Minister of Science and Technology of China No.2016YFA0202703(D.L.).

摘　　要：Engineering a complete,physiologically functional,periodontal complex structure remains a great clinical challenge due to the highly hierarchical architecture of the periodontium and coordinated regulation of multiple growth factors required to induce stem cell multilineage differentiation.Using biomimetic self-assembly and microstamping techniques,we construct a hierarchical bilayer architecture consisting of intrafibrillarly mineralized collagen resembling bone and cementum,and unmineralized parallel-aligned fibrils mimicking periodontal ligament.The prepared biphasic scaffold possesses unique micro/nano structure,differential mechanical properties,and growth factor-rich microenvironment between the two phases,realizing a perfect simulation of natural periodontal hard/soft tissue interface.The interconnected porous hard compartment with a Young’s modulus of 1409.00±160.83 MPa could induce cross-arrangement and osteogenic differentiation of stem cells in vitro,whereas the micropatterned soft compartment with a Young’s modulus of 42.62±4.58 MPa containing abundant endogenous growth factors,could guide parallel arrangement and fibrogenic differentiation of stem cells in vitro.After implantation in critical-sized complete periodontal tissue defect,the biomimetic bilayer architecture potently reconstructs native periodontium with the insertion of periodontal ligament fibers into newly formed cementum and alveolar bone by recruiting host mesenchymal stem cells and activating the transforming growth factor beta 1/Smad3 signaling pathway.Taken together,integration of self-assembly and microstamping strategies could successfully fabricate a hierarchical bilayer architecture,which exhibits great potential for recruiting and regulating host stem cells to promote synergistic regeneration of hard/soft tissues.

关 键 词：Biomimetic design Biphasic scaffold Mineralized collagen Micropatterned arrays Periodontium regeneration 

分 类 号：R31[医药卫生—基础医学]