ATG7-driven mitophagy in BMSC@CS hydrogel reprograms metabolism to boost bone regeneration

Area of Science:

• Biomaterials Science
• Cell Biology
• Regenerative Medicine

Background:

• Bone regeneration is hindered by poor stem cell metabolism and osteogenic potential.
• Mitochondrial homeostasis, regulated by mitophagy, is crucial for bone formation.
• The role of autophagy related gene 7 (ATG7) in bone regeneration is not well understood.

Purpose of the Study:

• To investigate the role of ATG7 in bone regeneration.
• To develop a novel biomaterial platform for enhanced stem cell delivery and function.
• To explore ATG7-mediated metabolic reprogramming for improved osteogenesis.

Main Methods:

• Overexpression of ATG7 in bone marrow mesenchymal stem cells (BMSCs).
• Encapsulation of ATG7-BMSCs within a thermoresponsive chitosan (CS) hydrogel.
• In vitro assays for mitochondrial function and osteogenic differentiation.
• In vivo studies using rat cranial and femoral defect models.

Main Results:

• ATG7 overexpression enhanced mitophagy, preserved mitochondrial integrity, and reduced ROS.
• ATG7 activation restored oxidative phosphorylation and promoted osteogenic differentiation via PI3K-AKT pathway.
• ATG7-BMSC@CS hydrogel significantly accelerated bone formation and mineral density in vivo.
• ATG7 deficiency impaired mitochondrial function and bone formation.

Conclusions:

• ATG7-driven mitophagy is a key regulator of osteogenic metabolism and bone formation.
• A smart, living hydrogel platform integrating metabolic reprogramming with stem cell delivery shows promise for bone repair.
• This strategy offers a new approach for metabolism-oriented bone regeneration.