Low intensity ultrasound therapy induces angiogenesis and persistent inflammation in the chronic phase of the healing process of third degree burn wounds experimentally induced in diabetic and non-diabetic rats

Abstract

PURPOSE:To evaluate the effects of low intensity ultrasound on the healing process of third degree burn wounds in experimentally induced diabetic Wistar rats. METHODS:One hundred rats were divided into: control group; non-diabetic treated group; diabetic control group; diabetic treated group. The therapy was performed with a 3MHz ultrasound application, pulsed emission at 100Hz frequency, modulated at 20% with a dosage of 0.5W/cm 2 during three minutes throughout 30 days. The surgical debridement of the wound was performed once at day 2. The wounds were morphometrically, macroscopically and microscopically evaluated at 3, 7, 14, 21 and 30 days. RESULTS:The wound contraction and collagen quantification were higher in all treated groups. Macroscopically, necrosis was higher in the diabetic control group. Granulation tissue was higher in treated groups during the proliferative and remodeling phase.Microscopically, there were greater mononuclear inflammatory infiltration, angiogenesis and fibroblast quantification in treated groups during the proliferative and remodeling phases.CONCLUSIONS: therapeutic ultrasound is beneficial in the inflammatory and proliferative phases of the healing process because it controlled the necrotic tissue, increased the granulation tissue and wound contraction. However in the remodeling phase it is not beneficial because of the continued angiogenesis and a mononuclear inflammatory infiltration.

Efficacy and Safety of Low-Frequency, Noncontact Airborne Ultrasound Therapy (Glybetac) For Neuropathic Diabetic Foot Ulcers: A Randomized, Double-Blind, Sham-Control Study

“…The proposed mechanism for its efficacy in chronic wounds include the ultrasound-generated mechanical energy stimulating signal transduction pathways involved in wound healing, that is, leukocyte adhesion, growth factor generation, fibroblast proliferation, and collagen production. [35][36][37][38][39] NLFU induces vibration and cavitation instigates acoustic streaming and generates micron-sized bubbles in the tissues and causes fluids to move along the boundaries of sound wave in the cell membranes, resulting in alteration of cellular function, enhanced protein synthesis, and also increased permeability of the cell membranes and vascular walls. 26,38 Increased macrophage responsiveness, increased fibrinolysis, and increased nitric oxide are other ultrasoundinduced cellular effects.…”

“…26,38 Increased macrophage responsiveness, increased fibrinolysis, and increased nitric oxide are other ultrasoundinduced cellular effects. 38,39 Ultrasound energy is also postulated to cause reduction of edema, inhibition of bacterial colonization, reduction of bacterial bioburden, and preventing biofilm formation. 37 Another critical factor for tissue repair and regeneration in chronic wounds is neovascularization.…”

“…In a diabetic mouse model, low-frequency ultrasound has been demonstrated to enhance angiogenesis and collagen deposition. 36,39 This increased vascularity is probably due to the increased expression of vascular endothelial growth factor and stromal cell-derived factor-1 (SDF-1) and angiogenic cytokines induced through modulation of the transcriptional regulation of these genes. 39 Stimulation of SDF-1 expression is important since SDF-1 has been shown to be downregulated in diabetes and is associated with a decreased capacity of diabetic wounds to recruit circulating progenitors that play an important role in the healing process.…”

Nanomedicine and advanced technologies for burns: Preventing infection and facilitating wound healing

“…In another study, Fantinati et al investigated chronic third-degree burn wounds and reported that low-intensity ultrasound could control the extent of tissue necrosis, enhance granulation tissue formation, as well as accelerate wound closure (via contraction). They suggested that ultrasound would have useful effects on the inflammatory and proliferative phases in burn treatment process; but could induce undesirable angiogenesis as well as inflammation in the remodeling phase [136].…”

In Vivo Assessments of Minocycline combined Hyaluronic Acid-mediated Ultrasound Therapy of Infected Wound in Rats

“…In addition, intergroup analysis (ND and D groups) showed less bone loss in the D group treated with SRP+SDT compared to the ND group treated with SRP. This could be explained by the ability of ultrasound to promote angiogenesis and collagen synthesis in damaged areas [26,27]. Gu XQ et al found that low-intensity pulsed ultrasound could facilitate the calcium salt deposition as well as new bone maturation [28].…”