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Min Rui1,2, Jiannan Mao1,2, Hongshuai Wu2

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Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Tissue Engineering

Background:

  • Hypoxia and oxidative stress impede tissue regeneration after injury.
  • Local oxygen supply is crucial for healing bone fractures and defects but remains a challenge.
  • Current strategies often fail to address the complex interplay of oxygen levels and oxidative damage.

Purpose of the Study:

  • To develop an innovative oxygenating hydrogel microsphere system for localized oxygen delivery and antioxidant properties.
  • To investigate the mechanism by which this system remodels the regenerative microenvironment.
  • To evaluate the efficacy of the system in promoting bone repair under hypoxic conditions.

Main Methods:

  • Loading CaO2@SiO2@PDA (CSP) nanoparticles into gelatin methacrylate anhydride (GelMA) microspheres (CSP-GM).
  • Characterizing CSP-GM for sustained oxygen release and free radical scavenging.
  • Assessing CSP-GM's impact on bone marrow stromal cell (BMSC) adhesion, proliferation, mitochondrial homeostasis, and antioxidant defense.
  • Evaluating the modulation of the Nrf2/HO-1 signaling pathway.
  • In vivo testing in rat femoral defects to assess bone formation and vascularization.

Main Results:

  • CSP-GM exhibited sustained oxygen release and broad-spectrum free radical scavenging.
  • The microspheres promoted BMSC adhesion, proliferation, and recovered mitochondrial function and antioxidant defenses.
  • CSP-GM synergistically produced oxygen and scavenged ROS, promoting angiogenesis and osteogenesis via the Nrf2/HO-1 pathway.
  • In vivo studies demonstrated enhanced vascularized bone formation in rat femoral defects.

Conclusions:

  • The developed CSP-GM system effectively provides localized oxygen and antioxidant support.
  • This functionalized micro-oxygen reservoir significantly enhances bone regeneration by modulating the cellular microenvironment.
  • The strategy presents a promising approach for treating bone defects and other hypoxic tissue injuries.