Stage-specific biomimetic nanoparticles reprogram osteoblast-adipocyte equilibrium for targeted osteoporosis therapy

  • Bioact Mater. 2026 May 13:64:455-470. doi: 10.1016/j.bioactmat.2026.05.004.
Kehan Cai  1 ,  Zhe Fan  1 ,  Jun Tan  2 ,  Wei Cai  1 ,  Minghang Zhang  1 ,  Haojie Tang  3 ,  Jianzhong Xu  1 ,  Han Lu  4 ,  Wei He  4 ,  Qian Xu  5 ,  Yazhou Chen  6 ,  Tao Chen  1
Affiliations
  • 1. Department of Orthopedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
  • 2. Department of Mini-invasive Spinal Surgery, The Third People's Hospital of Henan Province, Zhengzhou, 450000, China.
  • 3. Department of Orthopedics, The Third People's Hospital of Henan Province, Zhengzhou, 450052, China.
  • 4. Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450052, China.
  • 5. College of Life Science, Nanyang Normal University, Nanyang, 473061, China.
  • 6. Henan Institute of Advanced Technology, Zhengzhou University, Zhengzhou, 450001, China.
PMID: 42181171 DOI: 10.1016/j.bioactmat.2026.05.004
Abstract

Cell membrane-camouflaged nanoparticles have emerged as powerful tools for targeted drug delivery; however, current strategies typically utilize membranes from static cell states, overlooking the dynamic functional evolution that occurs during lineage commitment. Here, we established a stepwise osteogenic differentiation model for BMSCs and isolated cell membranes from distinct stages of this process to construct a series of cell membrane-camouflaged mesoporous silica nanoparticles (CM-MSNs). Proteomic profiling revealed stage-dependent remodeling of membrane protein composition, with early osteogenic (EO) stage membranes uniquely enriched in phosphatases and Cadherins. Functional evaluations showed stage-dependent activity among CM-MSNs, and EO membrane-camouflaged nanoparticles (EO-MSNs) exhibited the strongest capacity to promote calcium deposition and enhance BMSC osteogenesis in vitro via the Wnt/β-catenin signaling pathway. In a rat model of osteoporosis, EO-MSN exhibited prolonged circulation time, precise bone-specific accumulation, and potent anti-osteoporotic efficacy. Collectively, our findings suggest that utilizing stage-specific cell membranes offers a novel strategy to remodel the osteoporotic microenvironment by modulating the osteoblast-adipocyte equilibrium.

Keywords
Biomimetic nanoparticle; Bone formation; Osteogenic differentiation; Osteoporosis; Stepwise.
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