Introduction: While there is evidence of the beneficial effects of pulsed electromagnetic fields (PEMF) in bone healing, the mechanism of action remains unclear. Our laboratory has demonstrated that this may involve increased angiogenesis. We sought to examine another angiogenic process by studying wound healing under the influence of PEMF.
Methods: 5mm circular wounds were created on the dorsum of db/db (diabetic) and wild type C57BL6 mice, splinted open and covered with an occlusive dressing. Groups of both diabetic and wild-type mice were exposed to a clinical bone healing PEMF signal (4.5 ms burst duration/15Hz) 8 hrs/day for 14 days and compared with age-matched controls. Gross closure was assessed with photographic analysis of area changes over time. Histological examination assessed granulation and epithelial gap, cell proliferation (BrdU), and endothelial cell density (CD31). Growth factor analysis was performed on supernatants from PEMF-conditioned human vein umbilical cell cultures.
Results: Diabetic mice exposed to PEMF demonstrated accelerated wound closure by day 7 (PEMF: 60% vs. control: 78%, p<0.05) and day 14 (PEMF: 21% vs. control: 55%, p<0.05). Because wild-type mice heal twice as fast as diabetics, wounds were analyzed on days 4 and 8. Accelerated closure was evident in PEMF wild-type mice at day 4 (PEMF: 15% vs. 42%, p<0.05) and day 8 (8% vs. 28%, p<0.05). In wound bed histological sections, granulation and cell proliferation were both increased in PEMF treated diabetic mice (day 7: 52±8 vs. 31±5 cells per high power field (200x)). Immunohistochemical analysis revealed significantly higher CD31 density in diabetic wounds exposed to PEMF at day 7 (PEMF: 28±4 vs. control 17±4 vessels per high power field) and day 14 (PEMF: 32±6 vs. control: 21±5). Increases were also seen in wild-type C57BL6 mice at day 7 (PEMF: 41±7 vs. control: 28±6) and day 14 (PEMF: 48±5 vs. control: 40±5). HUVECs cultured in PEMF exhibited 5-fold higher levels of FGF2 compared to controls after as little as 30min (20.50 pg/ml±6.75 vs. 4.25pg/ml±0.75) with no change in VEGF.
Conclusions: Our findings indicate PEMF accelerates wound closure and increases endothelial cell proliferation. The observed release of FGF2 may account for the increased vascular density and accelerated wound closure and may also contribute to the beneficial effects of PEMF on bone healing. Other applications suggested by this study may include treatment of diabetic ulcers, other non-healing wounds, and vascular delay.