Porous Microspheres Loading Small Molecule Targeting REV-ERBs Modulate Inflammatory Cytokines Fluctuations to Promote...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Nanotechnology

Background:

• Alveolar bone loss, often caused by periodontitis, presents challenges for existing bone graft materials.
• Inflammation and disrupted cytokine homeostasis impede effective bone regeneration.

Purpose of the Study:

• To develop a novel microsphere system for alveolar bone repair by regulating inflammatory cytokines.
• To investigate the potential of targeting circadian rhythm genes for enhanced bone regeneration.

Main Methods:

• PLGA-S@Gel-SeHA microspheres were synthesized using iso-density emulsion and microfluidics.
• The microspheres incorporate Poly(lactic-co-glycolic acid) (PLGA), gelatin mineralized selenium-doped hydroxyapatite (Gel-SeHA), and STL1267 to target REV-ERBs.
• In vitro and in vivo studies were conducted using LPS stimulation and rat alveolar bone defects.

Main Results:

• Microspheres exhibited uniform size and porosity, enhancing cell adhesion and ingrowth.
• STL1267 sustained release mitigated inflammatory cytokine fluctuations (IL-6, TNF, IL-1β) by over 30%, restoring rhythmic expression.
• Promoted M2 macrophage polarization and demonstrated significant bone regeneration in rat models.

Conclusions:

• PLGA-S@Gel-SeHA microspheres effectively regulate inflammation and promote alveolar bone regeneration.
• Targeting circadian rhythm genes offers a promising anti-inflammatory strategy for bone repair.
• This approach holds potential for treating bone defects associated with periodontitis.