Reduced Oral Wound Healing in the NOD Mouse Model for Type 1 Autoimmune Diabetes and Its Reversal by Epidermal Growth Factor Supplementation

Abstract

Using the NOD mouse, a model for type 1 diabetes, we examined how reduced concentrations of epidermal growth factor (EGF) in the saliva, after onset of type 1 diabetes, affect oral wound healing. Diabetic NOD/LtJ mice on insulin therapy, prediabetic NOD/LtJ, and ageand sex-matched BALB/cJ mice were given a cutaneous tongue punch and allowed to undergo normal healing. With diabetes onset and a reduction in saliva-derived growth factor levels, the rate of tongue wound healing was reduced compared with nondiabetic NOD/LtJ and healthy BALB/cJ mice. Addition of exogenous EGF to the drinking water did not accelerate the rate of healing in BALB/cJ or prediabetic NOD/LtJ; however, diabetic NOD/LtJ mice exhibited accelerated wound healing similar to healthy mice. These results demonstrate that loss of growth factors from saliva is associated with profoundly reduced oral wound healing, suggesting that therapeutic treatment with topical delivery may be beneficial to patients with type 1 diabetes and oral wound complications.

The Effect of Hyperglycemia on Pulpal Healing in Rats

“…This correlation is directly related to the absence of a complete bridge formation in teeth with inflamed pulps. Our findings confirm previously cited assertions that there is a diminished healing response associated with diabetic subjects after dental procedures (19,20,22).…”

“…One of the hallmarks of this devastating disease is impaired wound healing (21). The implications of this finding with respect to oral wound healing is shown in diminished healing of cutaneous tongue punches in nonobese diabetic mice compared with their nondiabetic counterparts (22). Although disruption of the vasculature may partially explain the difference in healing pattern, other factors may also be responsible.…”

Nicotine Accelerates Angiogenesis and Wound Healing in Genetically Diabetic Mice

“…[3][4][5][6][7] Conversely, inhibitors of angiogenesis, such as TNP-470, delay wound repair in diabetic mice. 8 In humans, recombinant PDGF improved wound healing in patients suffering from cutaneous diabetic ulcers or pressure sores.…”

Saliva in Health and Disease, Chemical Biology of

“…Salivary EGF speeds up the healing process by its angiogenetic and cell proliferating effects (19,20). Other growth factors present in saliva (3) such as transforming growth factor beta, fibroblast growth factor, insulin like growth factors, and nerve growth factor also contribute to the healing process.…”