An Immunomodulating Regenerating Hydrogel That Rescues the Oxidative Microenvironment and Reverses Cell Senescence...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Nanotechnology

Background:

• Osteoporosis involves reduced bone mass, compromised bone structure, and elevated reactive oxygen species (ROS) and inflammation.
• ROS accumulation and inflammation lead to mitochondrial dysfunction and cellular senescence, hindering bone defect regeneration.

Purpose of the Study:

• To design and present a ROS-responsive hydrogel system (GHCZ) for scavenging ROS and reversing cellular senescence to accelerate bone regeneration in osteoporosis.
• To investigate the potential of HA-PBA coated Ce-ZOL nanocomposites within a hydrogel for treating osteoporotic bone defects.

Main Methods:

• Developed a hydrogel system (GHCZ) incorporating HA-PBA coated Ce-ZOL nanocomposites for sustained release.
• Evaluated the ROS scavenging, immunomodulatory (macrophage polarization), and anti-senescence effects of GHCZ on bone marrow stromal cells (BMSCs) and macrophages in vitro.
• Assessed the efficacy of GHCZ in promoting bone defect healing in vivo.

Main Results:

• GHCZ hydrogel sustained the release of Ce-ZOL nanoparticles, which effectively scavenged extracellular and intracellular ROS.
• GHCZ promoted M2 macrophage polarization, inhibited pro-inflammatory cytokines, reversed BMSC senescence, and enhanced osteogenic capacity by protecting mitochondrial function.
• In vitro and in vivo studies demonstrated that GHCZ significantly augmented bone repair.

Conclusions:

• The GHCZ hydrogel system exhibits powerful immunomodulation, favorable microenvironment reshaping, mitochondrial protection, and superior pro-osteogenic capacity.
• This GHCZ hydrogel offers a promising therapeutic strategy for treating osteoporotic bone defects by addressing ROS, inflammation, and senescence.