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University of California, Los Angeles

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J. Control. Release, Feb 20 2025, S0168-3659(25)00161-0 | https://doi.org/10.1016/j.jconrel.2025.02.048 Nanocomposite hydrogels optimize the microenvironment by exterior/interior crosstalk for reprogramming osteoporotic homeostasis in bone defect healing

Dengke Chen ^a,1, Yuying Yang ^a,d,1, Beibei Li ^a,1, Yingjuan Yao ^a, Junyi Xu^a, Rongyan Liu ^a, Jiao Peng ^a, Zhuangpeng Chang ^a, Rui Zhao ^a, Ruigang Hou ^a, Min Lee ^c, Xianghui Xu ^b, Xiao Zhang ^a

^aSchool of Pharmacy and Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China
^bDepartment of Pharmacy, College of Biology, Hunan University, Changsha, Hunan 410082, PR China
^cDivision of Oral and Systemic Health Sciences, University of California at Los Angeles, Los Angeles, CA 90095, USA
^dSchool of Pharmacy, Zhejiang University, Hangzhou, Zhejiang 310058, PR China

¹These authors contributed equally to this work.
Corresponding authors: Zhuangpeng Chang, Rui Zhao, Ruigang Hou, Min Lee, Xianghui Xu, Xiao Zhang

Abstract

Discovering new tactics for healing bone defects becomes a worldwide challenge in osteoporosis patients. The disordered acidic microenvironment plays a pivotal role in driving the imbalance of bone homeostasis regulated by osteoblasts and osteoclasts. However, the scarcity of hydrogel materials developed to optimize local bone microenvironment has made osteoporotic defect healing more challenging. Herein, we present innovative nanocomposite hydrogels with precisely engineered microarchitectures designed to optimize the acidic microenvironment by facilitating crosstalk between exterior and interior spaces, aimed at enhancing the reconstruction of osteoporotic bone defects. The chlorogenic acid grafted chitosan as double-sided crosslinkers is specially designed to not only combine with acid-reversible Laponite® nanosheet via interfacial interactions but also integrate with gold nanorod (a typical photothermal agent) through catechol-Au bond. The supramolecular construction of nanocomposite hydrogels holds promise for achieving a highly continuous and homogeneous pore network microarchitecture. As expected, hydrogels display outstanding spatiotemporal local mild hyperthermia, which accelerates the neutralization reaction between OH^- ions released from Laponite® and hydrogen ions (pH ~ 4.0). The optimized microenvironment restores osteoclast/osteoblast homeostasis, resulting in the promotion of osteoblastogenesis and inhibition of osteoclastogenesis, thereby facilitating the healing of osteoporotic bone defects. This work is hoped to design versatile hydrogels for optimizing the microenvironment, displaying promising integrative substitute materials for clinically effective treatment of osteoporotic bone defects.

논문정보

형식Research article
게재일2025년 02월 (BRIC 등록일 2025-02-24)
연구진국외 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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