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The existing drugs usually fail to re\u2010establish the osteoblast\/osteoclast balance from both sides and generate side\u2010effects owing to the lack of bone\u2010targeting ability. Here, engineered cell\u2010membrane\u2010coated nanogels PNG@mR&amp;C capable of scavenging receptor activator of nuclear factor\u2010\u03baB ligand (RANKL) and responsively releasing therapeutic PTH 1\u201334 in the bone microenvironment are prepared from RANK and CXCR4 overexpressed bone mesenchymal stem cell (BMSC) membrane\u2010coated chitosan biopolymers. The CXCR4 on the coated\u2010membranes confer bone\u2010targeting ability, and abundant RANK effectively absorb RANKL to inhibit osteoclastogenesis. Meanwhile, the release of PTH 1\u201334 triggered by osteoclast\u2010mediated acid microenvironment promote osteogenesis. In addition, the dose and frequency are greatly reduced due to the smart release property, prolonged circulation time, and bone\u2010specific accumulation. Thus, PNG@mR&amp;C exhibits satisfactory therapeutic effects in the ovariectomized (OVX) mouse model. This study provides a new paradigm re\u2010establishing the bone metabolic homeostasis from multitargets and shows great promise for the treatment of PMOP.<\/jats:p>","DOI":"10.1002\/smll.202303494","type":"journal-article","created":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T19:17:54Z","timestamp":1696533474000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["Bone\u2010Targeted Biomimetic Nanogels Re\u2010Establish Osteoblast\/Osteoclast Balance to Treat Postmenopausal Osteoporosis"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7532-0151","authenticated-orcid":false,"given":"Yongzhi","family":"Cui","sequence":"first","affiliation":[{"name":"Department of Orthopaedics Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai 200233 P. R. 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