Trifunctional Sialylation‐Based SF‐ZIF@NA Hydrogel for Selective Osteoclast Inhibition and Enhanced Bone‐Vessel Regeneration in Osteoporotic Bone Defects

Abstract Osteoporotic bone defects are challenging to repair due to imbalances in bone resorption and formation, coupled with insufficient vascularization. To address these issues, it develops a trifunctional hydrogel (SF‐ZIF@NA) designed to selectively inhibit osteoclast activity and enhance vascul...

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Main Authors: Zhengrong Chen, Wenxin Yang, Yong Tang, Qianqian Dong, Kui Huang, Jiulin Tan, Jie Zhang, Juan Cai, Qixiu Yu, Qijie Dai, Jianzhong Xu, Shuquan Guo, Ce Dou, Fei Luo
Format: Article
Language:English
Published: Wiley 2025-05-01
Series:Advanced Science
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Online Access:https://doi.org/10.1002/advs.202415895
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author Zhengrong Chen
Wenxin Yang
Yong Tang
Qianqian Dong
Kui Huang
Jiulin Tan
Jie Zhang
Juan Cai
Qixiu Yu
Qijie Dai
Jianzhong Xu
Shuquan Guo
Ce Dou
Fei Luo
author_facet Zhengrong Chen
Wenxin Yang
Yong Tang
Qianqian Dong
Kui Huang
Jiulin Tan
Jie Zhang
Juan Cai
Qixiu Yu
Qijie Dai
Jianzhong Xu
Shuquan Guo
Ce Dou
Fei Luo
author_sort Zhengrong Chen
collection DOAJ
description Abstract Osteoporotic bone defects are challenging to repair due to imbalances in bone resorption and formation, coupled with insufficient vascularization. To address these issues, it develops a trifunctional hydrogel (SF‐ZIF@NA) designed to selectively inhibit osteoclast activity and enhance vascularized bone regeneration. By enzymatically removing sialic acid, SF‐ZIF@NA prevents precursor osteoclasts (pOCs) from fusing into bone‐resorbing mature osteoclasts (mOCs), thereby preserving pOCs and their anabolic functions. Additionally, the hydrogel releases Zinc ion (Zn2⁺) in response to acidic conditions, promoting osteogenesis and angiogenesis. In vitro results confirmed that SF‐ZIF@NA impedes osteoclast fusion, enhances platelet‐derived growth factor‐BB (PDGF‐BB secretion from pOCs, and activates the FAK (focal adhesion kinase) signaling pathway to stimulate vascularized bone formation. In osteoporotic bone defect models, SF‐ZIF@NA accelerated bone repair with increased bone density and vascularization. These findings demonstrate that SF‐ZIF@NA offers a targeted and multifunctional strategy for osteoporotic bone regeneration by concurrently modulating osteoclast activity and promoting angiogenesis.
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institution OA Journals
issn 2198-3844
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spelling doaj-art-244f5b74279a4095ad752d5e93f19c282025-08-20T01:52:42ZengWileyAdvanced Science2198-38442025-05-011219n/an/a10.1002/advs.202415895Trifunctional Sialylation‐Based SF‐ZIF@NA Hydrogel for Selective Osteoclast Inhibition and Enhanced Bone‐Vessel Regeneration in Osteoporotic Bone DefectsZhengrong Chen0Wenxin Yang1Yong Tang2Qianqian Dong3Kui Huang4Jiulin Tan5Jie Zhang6Juan Cai7Qixiu Yu8Qijie Dai9Jianzhong Xu10Shuquan Guo11Ce Dou12Fei Luo13Department of Orthopedics Southwest Hospital Third Military Medical University (Army Medical University) Chongqing 400038 ChinaDepartment of Orthopedics Southwest Hospital Third Military Medical University (Army Medical University) Chongqing 400038 ChinaDepartment of Orthopedics Southwest Hospital Third Military Medical University (Army Medical University) Chongqing 400038 ChinaIntegrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City Biological Science Research Center Southwest University Chongqing 400716 ChinaDepartment of Orthopedics Southwest Hospital Third Military Medical University (Army Medical University) Chongqing 400038 ChinaDepartment of Orthopedics Southwest Hospital Third Military Medical University (Army Medical University) Chongqing 400038 ChinaDepartment of Orthopedics Southwest Hospital Third Military Medical University (Army Medical University) Chongqing 400038 ChinaDepartment of Orthopedics Southwest Hospital Third Military Medical University (Army Medical University) Chongqing 400038 ChinaDepartment of Orthopedics Southwest Hospital Third Military Medical University (Army Medical University) Chongqing 400038 ChinaDepartment of Orthopedics Southwest Hospital Third Military Medical University (Army Medical University) Chongqing 400038 ChinaDepartment of Orthopedics Southwest Hospital Third Military Medical University (Army Medical University) Chongqing 400038 ChinaDepartment of Orthopaedics The First Affiliated Hospital of Chongqing Medical University Chongqing 400042 ChinaDepartment of Orthopedics Southwest Hospital Third Military Medical University (Army Medical University) Chongqing 400038 ChinaDepartment of Orthopedics Southwest Hospital Third Military Medical University (Army Medical University) Chongqing 400038 ChinaAbstract Osteoporotic bone defects are challenging to repair due to imbalances in bone resorption and formation, coupled with insufficient vascularization. To address these issues, it develops a trifunctional hydrogel (SF‐ZIF@NA) designed to selectively inhibit osteoclast activity and enhance vascularized bone regeneration. By enzymatically removing sialic acid, SF‐ZIF@NA prevents precursor osteoclasts (pOCs) from fusing into bone‐resorbing mature osteoclasts (mOCs), thereby preserving pOCs and their anabolic functions. Additionally, the hydrogel releases Zinc ion (Zn2⁺) in response to acidic conditions, promoting osteogenesis and angiogenesis. In vitro results confirmed that SF‐ZIF@NA impedes osteoclast fusion, enhances platelet‐derived growth factor‐BB (PDGF‐BB secretion from pOCs, and activates the FAK (focal adhesion kinase) signaling pathway to stimulate vascularized bone formation. In osteoporotic bone defect models, SF‐ZIF@NA accelerated bone repair with increased bone density and vascularization. These findings demonstrate that SF‐ZIF@NA offers a targeted and multifunctional strategy for osteoporotic bone regeneration by concurrently modulating osteoclast activity and promoting angiogenesis.https://doi.org/10.1002/advs.202415895bone regenerationosteoporosispdgf‐bbsialylationvascularization
spellingShingle Zhengrong Chen
Wenxin Yang
Yong Tang
Qianqian Dong
Kui Huang
Jiulin Tan
Jie Zhang
Juan Cai
Qixiu Yu
Qijie Dai
Jianzhong Xu
Shuquan Guo
Ce Dou
Fei Luo
Trifunctional Sialylation‐Based SF‐ZIF@NA Hydrogel for Selective Osteoclast Inhibition and Enhanced Bone‐Vessel Regeneration in Osteoporotic Bone Defects
Advanced Science
bone regeneration
osteoporosis
pdgf‐bb
sialylation
vascularization
title Trifunctional Sialylation‐Based SF‐ZIF@NA Hydrogel for Selective Osteoclast Inhibition and Enhanced Bone‐Vessel Regeneration in Osteoporotic Bone Defects
title_full Trifunctional Sialylation‐Based SF‐ZIF@NA Hydrogel for Selective Osteoclast Inhibition and Enhanced Bone‐Vessel Regeneration in Osteoporotic Bone Defects
title_fullStr Trifunctional Sialylation‐Based SF‐ZIF@NA Hydrogel for Selective Osteoclast Inhibition and Enhanced Bone‐Vessel Regeneration in Osteoporotic Bone Defects
title_full_unstemmed Trifunctional Sialylation‐Based SF‐ZIF@NA Hydrogel for Selective Osteoclast Inhibition and Enhanced Bone‐Vessel Regeneration in Osteoporotic Bone Defects
title_short Trifunctional Sialylation‐Based SF‐ZIF@NA Hydrogel for Selective Osteoclast Inhibition and Enhanced Bone‐Vessel Regeneration in Osteoporotic Bone Defects
title_sort trifunctional sialylation based sf zif na hydrogel for selective osteoclast inhibition and enhanced bone vessel regeneration in osteoporotic bone defects
topic bone regeneration
osteoporosis
pdgf‐bb
sialylation
vascularization
url https://doi.org/10.1002/advs.202415895
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