Brasenia-inspired hydrogel with sustained and sequential release of BMP and WNT activators for improved bone regeneration |
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| Institution: | 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;1. Department of Orthopaedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China;2. Medical Research Center, Guangdong Provincial People''s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China;3. School of Science and Engineering, Shenzhen Institute of Aggregate Science and Technology, The Chinese University of Hong Kong, Shenzhen 518172, China;4. Laboratory for Neuroscience in Health and Disease, Guangzhou First People''s Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China;5. School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, China;1. Key Laboratory of Thermo-Fluid Science and Engineering of Ministry of Education, School of Energy and Power Engineering, Frontier Institute of Science and Technology, Xi''an Jiaotong University, Xi''an 710054, China;2. School of Chemistry, Xi''an Key Laboratory of Sustainable Energy Materials Chemistry, Xi''an Jiaotong University, Xi''an 710049, China;3. School of Materials Science and Engineering, Xi''an Jiaotong University, Xi''an 710049, China;1. Department of Environmental Science and Engineering, Xi''an Jiaotong University, Xi''an 710049, China;2. Research Institute of Xi''an Jiaotong University, Hangzhou 311200, China;1. Department of Natural Medicine, School of Pharmacy, Fudan University, Shanghai 201203, China;2. The Institutes of Integrative Medicine of Fudan University, Shanghai 200040, China;3. Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China;1. Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China;2. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China |
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| Abstract: | 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 qRT-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. |
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