Systemic translation of locally infiltrated epidermal growth factor in diabetic lower extremity wounds

Abstract

Diabetic foot ulcer is one of the most frightened diabetic complications leading to amputation disability and early mortality. Diabetic wounds exhibit a complex networking of inflammatory cytokines, local proteases, and reactive oxygen and nitrogen species as a pathogenic polymicrobial biofilm, overall contributing to wound chronification and host homeostasis imbalance. Intralesional infiltration of epidermal growth factor (EGF) has emerged as a therapeutic alternative to diabetic wound healing, reaching responsive cells while avoiding the deleterious effect of proteases and the biofilm on the wound's surface. The present study shows that intralesional therapy with EGF is associated with the systemic attenuation of pro‐inflammatory markers along with redox balance recovery. A total of 11 diabetic patients with neuropathic foot ulcers were studied before and 3 weeks after starting EGF treatment. Evaluations comprised plasma levels of pro‐inflammatory, redox balance, and glycation markers. Pro‐inflammatory markers such as erythrosedimentation rate, C‐reactive protein, interleukin‐6, soluble FAS, and macrophage inflammatory protein 1‐alpha were significantly reduced by EGF therapy. Oxidative capacity, nitrite/nitrate ratio, and pentosidine were also reduced, while soluble receptor for advanced glycation end‐products significantly increased. Overall, our results indicate that the local intralesional infiltration of EGF translates in systemic anti‐inflammatory and antioxidant effects, as in attenuation of the glycation products' negative effects.

Epidermal growth factor effect on lipopolysaccharide-induced inflammation in fibroblasts derived from diabetic foot ulcer

“…Our study showed that fibroblasts, particularly DFU-derived ones, not only act as sentinel cells, 57 but also respond to therapeutic stimuli such as EGF, by decreasing the aberrant activation of the TLR signalling pathways and, consequently, the levels of inflammatory mediators. These results contribute to explain our previous in vivo observations about the reduction of circulating levels of inflammatory cytokines after local administration of human recombinant EGF in DFU, 18 which stimulate granulation and wound closure in diabetic patients.…”

Epidermal Growth Factor in Healing Diabetic Foot Ulcers: From Gene Expression to Tissue Healing and Systemic Biomarker Circulation

“…This was the fi rst clinical validation of in vitro and animal data indicating that EGF's cytoprotective eff ect is at least partially mediated by correcting the redox balance. [18,73,[76][77][78] A more recent study by García-Ojalvo and colleagues [79] confi rmed previous observations concerning the systemic impact of locally-infi ltrated EGF on reestablishment of a physiological redox balance. Moreover, the new data indicates that EGF's eff ect extends to reduction of diabetic endovascular pro-infl ammatory markers.…”

A Randomized Controlled Trial on the Effectiveness of Epidermal Growth Factor-Containing Ointment on the Treatment of Solar Lentigines as Adjuvant Therapy

“…Furthermore, EGF may have inhibitory effects on melanogenesis by reduction of inflammation and promotion of effects on the regeneration of the epidermal barrier in damaged tissues [33,34]. The antioxidant effect of EGF could also induce anti-melanogenesis [16,35]. However, there are few clinical studies evaluating the anti-pigmentation effect of EGF on pigmentary disorders [12].…”

“…In actual practice, EGF is commonly used to treat chronic skin ulcers, including diabetic foot ulcers and burn injuries [14,15]. It has been reported that EGF has anti-inflammatory and antioxidant effects and directly lowers melanin production [12,13,16]. Based on this action, the possibility of the applicability of EGF on antipigmentation has recently been proposed.…”