Injectable decellularized dental pulp matrix-functionalized hydrogel microspheres for endodontic regeneration

作者全名："Zheng, Liwen; Liu, Yaxian; Jiang, Lin; Wang, Xiaoping; Chen, Yuqin; Li, Lan; Song, Mingyu; Zhang, Hongmei; Zhang, Yu Shrike; Zhang, Ximu"

作者地址："[Zheng, Liwen; Liu, Yaxian; Jiang, Lin; Wang, Xiaoping; Zhang, Hongmei; Zhang, Ximu] Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing, Peoples R China; [Zheng, Liwen; Liu, Yaxian; Jiang, Lin; Wang, Xiaoping; Chen, Yuqin; Li, Lan; Song, Mingyu; Zhang, Hongmei; Zhang, Ximu] Chongqing Med Univ, Stomatol Hosp, Chongqing 401174, Peoples R China; [Zhang, Yu Shrike] Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing, Peoples R China; [Zhang, Yu Shrike] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Engn Med, Cambridge, MA 02139 USA"

通信作者："Zhang, HM; Zhang, XM (通讯作者)，Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing, Peoples R China.; Zhang, YS (通讯作者)，Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Engn Med, Cambridge, MA 02139 USA."

来源：ACTA BIOMATERIALIA

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:000924404600001

JCR分区：Q1

影响因子：9.7

年份：2023

卷号：156

期号：　

开始页：37

结束页：48

文献类型：Article

关键词：Dental pulp; Endodontic regeneration; Hydrogel microspheres; Decellularized matrix

摘要："The sufficient imitation of tissue structures and components represents an effective and promising approach for tissue engineering and regenerative medicine applications. Dental pulp disease is one of the most common oral diseases, although functional pulp regeneration remains challenging. Herein, we pro-pose a strategy that employs hydrogel microspheres incorporated with decellularized dental pulp matrix-derived bioactive factors to simulate a pulp-specific three-dimensional (3D) microenvironment. The den-tal pulp microenvironment-specific microspheres constructed by this regenerative strategy exhibited favorable plasticity, biocompatibility, and biological performances. Human dental pulp stem cells (hDPSCs) cultured on the constructed microspheres exhibited enhanced pulp-formation ability in vitro . Further-more, the hDPSCs-microcarriers achieved the regeneration of pulp-like tissue and new dentin in a semi-orthotopic model in vivo. Mechanistically, the decellularized pulp matrix-derived bioactive factors mediated the multi-directional differentiation of hDPSCs to regenerate the pulp tissue by eliciting the secretion of crucial bioactive cues. Our findings demonstrated that a 3D dental pulp-specific microenvironment facilitated by hydrogel microspheres and dental pulp-specific bioactive factors regenerated the pulp-dentin complex and could be served as a promising treatment option for dental pulp disease.Statement of significanceInjectable bioscaffolds are increasingly used for regenerative endodontic treatment. Despite their success related to their ability to load stem cells, bioactive factors, and injectability, conventional bulk bioscaffolds have drawbacks such as ischemic necrosis in the central region. Various studies have shown that ischemic necrosis in the central region can be corrected by injectable hydrogel microspheres. Unfortunately, pris-tine microspheres or microspheres without dental pulp-specific bioactive factor would oftentimes fail to regulate stem cells fates in dental pulp multi-directional differentiation. Our present study reported the biofabrication of dental pulp-derived decellularized matrix functionalized gelatin microspheres, which contained dental pulp-specific bioactive factors and have the potential application in endodontic regeneration.(c) 2022 Published by Elsevier Ltd on behalf of Acta Materialia Inc."

基金机构："National Natural Science Foundation of China [32070826, 81870758]; Chongqing Science and Health Joint Medical project [2020GDRC017]; CQMU Program for Youth Innovation in Future Medicine [W0075]; Senior Medical Talents Program of Chongqing for Young and Middle-aged, Natural Science Foundation of Chongqing [cstc2021jcyj-msxmX0560]; Chongqing Health Commission [2021MSXM209]; Bureau of Science and Technology of Yubei, Chongqing [2021 (12)]; Brigham research institute"

基金资助正文："This work was financed by the National Natural Science Foundation of China (32070826 , 81870758) , Chongqing Science and Health Joint Medical project (2020GDRC017) , CQMU Program for Youth Innovation in Future Medicine (W0075) , Senior Medical Talents Program of Chongqing for Young and Middle-aged, Natural Science Foundation of Chongqing (cstc2021jcyj-msxmX0560) , Chongqing Health Commission (2021MSXM209) , Bureau of Science and Technology of Yubei, Chongqing (#2021 (12) ) . Y.S.Z. was not supported by any of these funds and Brigham research institute has been thanked."