Type 2 diabetes impairs angiogenesis and osteogenesis in calvarial defects: MicroCT study in ZDF rats

The present study was motivated by the fact that bone regeneration in the compromised vascular microenvironment of T2DM is challenging and the factors that determine the adverse bone regeneration outcomes are poorly understood. For this purpose the effect of T2DM on osteogenic and angiogenic healing potential of calvarial bone, was evaluated in Zucker diabetic fatty (ZDF) rats, an established rat model for obese T2DM.

The study used 16-week-old ZDF rats and their age-matched controls, Zucker Lean (ZL). Circular defects of different sizes were created on the animal calvaria, either a single 8-mm-diameter (n = 6) defect, or 6-4-2-mm-diameter multidefects (n = 6). Bone regeneration was evaluated at 0, 4, 6 and 8 weeks post surgery using in vivo micro-CT and after animal sacrifice using ex vivo micro-CT. Vascular network parameters within the defects, were quantified by perfusing the animal vasculature with microfil® and scanning it after decalcification.

Compared to results obtained from the ZL rats, defects of 8-mm-diameter in ZDF rats displayed impaired healing kinetics and significantly reduced newly formed bone volume (p < 0.01) and surface area (p < 0.01), 8 weeks post surgery. Defects of 6-4-2-mm-diameter exhibited bone formation, which was independent of either the size or the diabetic condition. Compared to results from the ZL, in the ZDF rats, vasculature volume and surface area were significantly (p < 0.05) reduced in all size-defects.

The present study provided evidence that T2DM impairs bone formation in critical-size calvarial defects and markedly reduces angiogenesis in all defects regardless of the defect size tested.