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Microenvironment-responsive trilayered bionic periosteum enhances osteogenic-angiogenic coupling for sequential bone

Xingbang Ruan1, Yingchuang Tang1, Kai Zhang1

  • 1Department of Orthopedic Surgery, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, Jiangsu, China.

Biomaterials
|December 5, 2025
PubMed
Summary

This study introduces a novel bionic periosteum that sequentially enhances bone regeneration by reducing oxidative stress and promoting coordinated bone and blood vessel growth, addressing critical challenges in severe bone defect treatment.

Keywords:
Bionic periosteumBone regenerationOsteogenic-angiogenic couplingReactive oxygen species

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Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Tissue Engineering

Background:

  • Severe bone defects pose significant clinical challenges due to the lack of periosteum and osteogenic blood vessels.
  • Elevated reactive oxygen species (ROS) during early bone regeneration impair mitochondrial function and osteogenic potential.

Purpose of the Study:

  • To develop a microenvironment-responsive, trilayered bionic periosteum (NMC@POB) for sequential bone regeneration.
  • To promote osteogenic-angiogenic coupling for enhanced healing of severe bone defects.

Main Methods:

  • Constructed a trilayered bionic periosteum with ROS-scavenging outer layer (tannic acid-cerium nanozymes), structural middle layer (polylactic acid), and osteoinductive inner core (oxidized xyloglucan-BMP2).
  • Evaluated NMC@POB in vitro and in a rat calvarial defect model.
  • Utilized transcriptomic analysis to investigate underlying molecular pathways.

Main Results:

  • NMC@POB effectively reduced oxidative stress and improved mitochondrial function.
  • Demonstrated coordinated osteogenesis and angiogenesis in vivo.
  • Transcriptomic analysis revealed activation of the Wnt/β-catenin pathway, promoting bone formation and neovascularization genes.

Conclusions:

  • The developed trilayered bionic periosteum (NMC@POB) is a promising strategy for orchestrated bone regeneration.
  • This microenvironment-responsive approach addresses critical factors limiting healing in severe bone defects.
  • The study highlights the potential of combining ROS scavenging with controlled release of osteoinductive factors for enhanced bone repair.