To test the hypothesis that oral Metformin accelerates fracture healing by enhancing AMPK-driven mitochondrial activity and reducing HMGB1-mediated inflammatory stress.
Approach:
Study Design: A rat open femoral fracture model was used, with histological, immunohistochemical, micro-computed tomography (micro-CT), and biomechanical analyses conducted to evaluate the effects of Metformin on fracture healing.
Animal Model: Female Sprague–Dawley rats (10 weeks old) were selected, with a total of 38 rats used across pilot and validation studies.
Surgical Procedure: An open mid-shaft femoral fracture was surgically created, followed by stabilization and post-operative care to minimize discomfort.
Key Findings:
Metformin enhances angiogenesis and osteogenic differentiation through AMPK activation.
Metformin improves mitochondrial biogenesis critical for bone remodeling.
The study evaluates the transition from cartilage to bone and earlier remodeling during fracture repair.
Interpretation:
The findings indicate that Metformin may address metabolic and inflammatory challenges in fracture healing.
Limitations:
The study was conducted in a rat model, which may not fully replicate human fracture healing.
Potential variability in biological responses to Metformin based on individual animal conditions.
Conclusion:
Metformin may enhance fracture healing, necessitating further investigation.
