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Bone Remodeling and Repair01:31

Bone Remodeling and Repair

Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during bone...

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Micropore-Confined ROS-Responsive 3D-Printed Shell-Core Scaffolds for Long-Term NO Release to Orchestrate

Jiali Guo1,2, Weihang Guo1, Haoming Lin1

  • 1Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, Department of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen, China.

Advanced Materials (Deerfield Beach, Fla.)
|February 24, 2026
PubMed
Summary

A novel scaffold delivers nitric oxide (NO) sustainably for 3 months, enhancing diabetic bone defect healing by neutralizing reactive oxygen species (ROS) and promoting vascular-osteogenic coupling.

Keywords:
3D‐printed scaffoldbone‐vascularized reconstructiondiabetic bone defect repairmicroporous shell‐nucleus structuresustained NO release

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Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Tissue Engineering

Background:

  • Diabetic bone defect healing is hindered by inflammation, oxidative stress, and poor vascularization.
  • Nitric oxide (NO) has therapeutic potential but suffers from short half-life and uncontrolled release.
  • Existing delivery systems fail to provide sustained NO for chronic diabetic bone repair.

Purpose of the Study:

  • To develop a micropore-confined, sustained nitric oxide (NO) delivery system for diabetic bone regeneration.
  • To engineer a scaffold that precisely controls L-arginine (L-Arg) release for on-demand NO generation.
  • To investigate the therapeutic effects of sustained NO release on modulating the diabetic bone microenvironment.

Main Methods:

  • Fabrication of a 3D printed scaffold using phase separation, with a ROS-degradable hydrogel core (L-Arg) and nHA/PCL shell.
  • Micropore confinement strategy to control L-Arg release and in situ NO generation.
  • In vitro and in vivo studies to evaluate scaffold performance, NO release kinetics, and bone regeneration efficacy.

Main Results:

  • The scaffold provided sustained NO release for 3 months, avoiding burst toxicity.
  • Micropore confinement enabled controlled L-Arg release and localized ROS/L-Arg reaction for NO generation.
  • The system effectively neutralized ROS, promoted M2 macrophage polarization, enhanced angiogenesis, and stimulated osteogenic differentiation in vitro and in vivo.

Conclusions:

  • The micropore-confined scaffold offers a versatile platform for sustained, on-demand NO delivery in complex pathological conditions.
  • This approach synergistically enhances diabetic bone regeneration by modulating inflammation, oxidative stress, and vascular-osteogenic coupling.
  • The developed system represents a promising strategy for treating chronic diabetic bone defects.