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Peptides from Phage Display Library Modulate Gene Expression in Mesenchymal Cells and Potentiate Osteogenesis in Unicortical Bone Defects
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Milk EVs Promote Apical Periodontitis Bone Repair via Osteoblast Targeting.

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Engineered milk-derived extracellular vesicles (MEVs) target osteoblasts to repair bone destruction in chronic apical periodontitis (CAP). These DPS-MEVs activate oxidative phosphorylation and promote M2 macrophage polarization for enhanced bone regeneration and reduced inflammation.

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apical periodontitismilk-derived extracellular vesiclesosteoblast targeting

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Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Immunology

Background:

  • Chronic apical periodontitis (CAP) causes alveolar bone loss, and current treatments lack specificity for bone repair.
  • Extracellular vesicles (EVs), especially milk-derived EVs (MEVs), show promise for bone regeneration and possess anti-inflammatory properties.

Purpose of the Study:

  • To investigate the therapeutic efficacy of engineered MEVs, modified with an osteoblast-targeting peptide (DPS), for treating CAP.
  • To evaluate the potential of DPS-modified MEVs in enhancing osteogenesis and promoting bone repair in a CAP model.

Main Methods:

  • Engineered MEVs with an osteoblast-targeting peptide (DPS-MEVs) were developed.
  • In vitro and in vivo studies assessed DPS-MEVs' osteogenic capacity, osteoblast targeting, and mechanism of action (OXPHOS activation via KLF4/Ndufa4).
  • DPS-MEVs were transplanted into a canine CAP model via apical microsurgery to evaluate bone repair and anti-inflammatory effects.

Main Results:

  • DPS-MEVs demonstrated enhanced osteoblast targeting and osteogenic capacity compared to unmodified MEVs.
  • Osteoblast targeting and osteogenesis were mediated by KLF4-induced upregulation of Ndufa4, activating oxidative phosphorylation (OXPHOS).
  • In vivo, DPS-MEVs promoted M2 macrophage polarization, leading to enhanced bone repair and reduced inflammation in the canine CAP model.

Conclusions:

  • Engineered DPS-MEVs represent a promising dual-functional therapy for CAP, addressing both tissue repair and immunomodulation.
  • This approach offers potential for precision treatment of inflammatory bone diseases by targeting osteoblasts and modulating the immune response.