Bioelectrically Reprogramming Hydrogels Rejuvenate Vascularized Bone Regeneration in Senescence

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Tissue Engineering

Background:

• Senescent bone tissue exhibits impaired healing due to decreased angiogenesis, disrupted bioelectric signaling, and ion dysregulation.
• Age-related bone defects present significant challenges for repair because of these pathological imbalances.

Purpose of the Study:

• To develop a synergistic therapeutic strategy for senile bone defects using a conductive hydrogel.
• To investigate the hydrogel's ability to reverse pathological imbalances and promote vascularized bone regeneration.

Main Methods:

• A conductive hydrogel was developed, doped with magnesium ion (Mg2+)-modified black phosphorus (BP).
• The hydrogel's effects on bioelectric signals, ion homeostasis, and cellular pathways were analyzed in aged bone defect models.
• Vascular endothelial growth factor (VEGF) and calcium ion (Ca2+) signaling were assessed, alongside stem cell differentiation markers.

Main Results:

• The hydrogel effectively reprogrammed electrical signals and restored Mg2+ homeostasis in senile bone defects.
• It significantly promoted blood vessel regeneration by increasing VEGF and VEGFR2 expression via the PI3K-AKT-eNOS pathway.
• The hydrogel normalized Ca2+ influx and enhanced osteogenic differentiation of senescent stem cells.

Conclusions:

• The conductive hydrogel synergistically restores chemical and bioelectric signals, crucial for bone repair.
• This innovative treatment restores bone-vascular coupling and achieves effective vascularized bone regeneration in aged bone defects.
• The strategy holds significant potential for treating senile bone defects and related conditions.