Stem Cell-Niche Engineering via Multifunctional Hydrogel Potentiates Stem Cell Therapies for Inflammatory Bone Loss

作者全名："Li, Gang; Li, Zimeng; Li, Lanlan; Liu, Shan; Wu, Peng; Zhou, Min; Li, Chenwen; Li, Xiaodong; Luo, Gaoxing; Zhang, Jianxiang"

作者地址："[Li, Gang; Li, Zimeng; Li, Lanlan; Liu, Shan; Wu, Peng; Li, Chenwen; Zhang, Jianxiang] Third Mil Med Univ Army Med Univ, Coll Pharm, Dept Pharmaceut, Chongqing 400038, Peoples R China; [Li, Zimeng; Li, Xiaodong] Zhejiang Univ, Stomatol Hosp, Sch Med,Key Lab Oral Biomed Res Zhejiang Prov, Sch Stomatol,Zhejiang Prov Clin Res Ctr Oral Dis, Hangzhou 310006, Peoples R China; [Liu, Shan] Chongqing Med Univ, Chongqing Key Lab Oral Dis & Biomed Sci, Coll Stomatol, Chongqing 401147, Peoples R China; [Wu, Peng] Vocat & Tech Coll, Coll Pharm & Med Technol, Hanzhong 723000, Shaanxi, Peoples R China; [Zhou, Min; Luo, Gaoxing; Zhang, Jianxiang] Third Mil Med Univ Army Med Univ, Southwest Hosp, Inst Burn Res, State Key Lab Trauma Burn & Combined Injury, Chongqing 400038, Peoples R China"

通信作者："Zhang, JX (通讯作者)，Third Mil Med Univ Army Med Univ, Coll Pharm, Dept Pharmaceut, Chongqing 400038, Peoples R China.; Li, XD (通讯作者)，Zhejiang Univ, Stomatol Hosp, Sch Med,Key Lab Oral Biomed Res Zhejiang Prov, Sch Stomatol,Zhejiang Prov Clin Res Ctr Oral Dis, Hangzhou 310006, Peoples R China.; Luo, GX; Zhang, JX (通讯作者)，Third Mil Med Univ Army Med Univ, Southwest Hosp, Inst Burn Res, State Key Lab Trauma Burn & Combined Injury, Chongqing 400038, Peoples R China."

来源：ADVANCED FUNCTIONAL MATERIALS

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:000878785800001

JCR分区：Q1

影响因子：19

年份：2022

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：bone loss; cell therapies; hydrogels; inflammation; periodontitis; stem cell niche

摘要："Effective therapies capable of simultaneously inhibiting inflammation and promoting bone healing remain to be developed for inflammatory bone disease. Stem cell therapies hold great promise for a variety of diseases, but their translation is hampered by low cell survival, rapid clearance, and limited functional integration of transplanted stem cells in target tissues. Herein, a multifunctional hydrogel-based stem cell niche engineering strategy is reported for the treatment of inflammatory bone loss. By rationally integrating different functional modules, an injectable hydrogel-based stem niche is engineered, which possesses temperature-triggered gelling performance, inflammation/oxidative stress-resolving activity, stem-cell binding and survival-enhancing capacity, and osteogenesis-promoting capability. Using ectomesenchymal stem cells (EMSCs), effectiveness of this functionally advanced synthetic stem cell niche is demonstrated in rats with periodontitis, a representative inflammatory bone loss disease. Synergistic effects of the multifunctional hydrogel and EMSCs are also confirmed, with respect to normalizing the pathological microenvironment and improving alveolar bone regeneration in the periodontal tissue. Mechanistically, inflammation/oxidative stress-resolving and osteogenic differentiation promoting capacities of the synthetic stem cell niche are mainly achieved by an incorporated nanotherapy via the GDF15/Atf3/c-Fos axis of the MAPK signaling pathway. Besides periodontitis, the newly engineered hydrogel-stem cell therapies are promising for the treatment of other inflammatory bone defects."

基金机构：National Natural Science Foundation of China [81901866]; Program for Scientific and Technological Innovation Leader of Chongqing [CQYC20210302362]; Natural Science Foundation of Chongqing [cstc2021jcyj-msxmX0414]; National Key R&D Program of China [2021YFA1101100]; Program for Distinguished Young Scholars of TMMU

基金资助正文："G.L. and Z.M.L. contributed equally to this work. This study was supported by the National Natural Science Foundation of China (No. 81901866), the Program for Scientific and Technological Innovation Leader of Chongqing (No. CQYC20210302362), the Natural Science Foundation of Chongqing (No. cstc2021jcyj-msxmX0414), the National Key R&D Program of China (No. 2021YFA1101100), and the Program for Distinguished Young Scholars of TMMU. All animal experiments were performed in line with the Guide for the Care and Use of Laboratory Animals proposed by National Institutes of Health. All procedures and protocols were approved by the Animal Ethics Committee at Third Military MedicYa), approval no. AMUWEC2020972."