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Brasenia-inspired hydrogel with sustained and sequential release of BMP and WNT activators for improved bone regeneration

查看全文 作　　者：Xinqing [1]Hao;Xuewei [2,3]Zhang;Yue [4]Hu;Chunxia [1]Ren;Cangwei [4]Liu;Lu [1]Wang;Yijun [4]Zhou;Shuangshuang [3]Wang;Huanyu [1,5]Luo;Guangxing [1,5]Yan;Xiao [1,5]Wang;Xiaomeng [1,5]Wang;Feilong [1,5]Ren;Ce [1,5]Shi,;Wenlong [3]Song;Hongchen [1,5]Sun 高影响力作者 机构地区：[1]Hospital of Stomatology,Jilin University,Changchun 130021,China;[2]School of Materials Science and Engineering,Hainan University,Haikou 570228,China;[3]State Key Laboratory of Supramolecular Structure and Materials,College of Chemistry,Jilin University,Changchun 130012.China;[4]School of Stomatology,China Medical University,Shenyang 110001,China;[5]jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling,Changchun 130021,China高影响力机构 出　　处：《Chinese Chemical Letters》索引2023年第34卷第7期,共7页高影响力期刊 基　　金：supported by the National Natural Science Foundation of China (Nos. 81970903 and 81920108012);Fundamental Research Funds for the Central Universities,Jilin Provincial Science & Technology Department (No. 20200201527JC);Jilin Department of Health (No. 2019Q013);Department of Finance of Jilin Province (No. JCSZ2019378-6)。 摘　　要：Although bone morphogenetic protein(BMP) and WNT signaling play pivotal roles in bone development,homeostasis, and regeneration, the applications of proteins to stimulate corresponding signaling pathways showed limited outcomes in the repair and regeneration of bone defects that might be attributed to the reciprocal interventions of these pathways. In order to satisfy the combinational and sequential activation of BMP and WNT pathways, inspired by the heterogeneous hydrogel-liked structures of Brasenia, heterogeneous alginate/chitosan hydrogels were fabricated and spatially loaded with FK506 and BIO to achieve sustained and sequential release of the activators. Alkaline phosphatase staining, alizarin red staining and q RT-PCR results suggested that FK506 and BIO enhanced osteoblastic differentiation in vitro when used separately. Besides, by mixing and matching the activators and the hydrogel layers, a superior releasing mode that a combination of early FK506 release and following BIO release was identified via both in vitro and in vivo explorations for most efficient bone regeneration. These results suggested that drug-loaded heterogeneous hydrogels possess great potentials in treating bone loss defects for future clinical practice. 关 键 词：Bone regeneration FK506 BIO Heterogeneous hydrogels Osteogenic differentiation
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