Development of Low Frequency (20–100 kHz) Clinically Viable Ultrasound Applicator for Chronic Wound Treatment

Abstract

This paper details the systematic approach used to develop a viable clinical prototype of a therapeutic ultrasound applicator and discusses the rationale and deliberations that led to the design strategy. The applicator was specifically devised to treat chronic wounds and - to the best of the author's knowledge - is the first truly wearable device with a proven record of reducing healing time, directly translating to a reduction of healthcare costs. The prototype operates in the kHz (20-100) range of frequencies and uses non-cavitational and non-thermal levels of ultrasound energy. Hence, in the absence of inertial cavitation and temperature elevation, the tissue-ultrasound interaction is considered to be dependent on stable cavitation (if any) and radiation force. The peak acoustic output pressure amplitude is limited to 55 kPa, corresponding to a spatial peak temporal peak intensity of 100 mW/cm2. This level of intensity is considered to be safe to apply for extended (up to four hours) periods of time. The patch-like applicator design is suitable to be embedded in wound dressing. With its light weight (<20g) and circular (40 mm dia) disk shape architecture, the applicator is well suited for chronic wound treatment. A small (n=8) pilot study on the effects of the applicator on diabetic ulcers healing time is presented. The average time to wound closure was 4.7 weeks for subjects treated with the active ultrasound applicator, compared to 12 weeks for subjects treated with a sham applicator, suggesting that patients with diabetic ulcers may benefit from the proposed treatment.

Gene Expression Changes in Therapeutic Ultrasound-Treated Human Chronic Wound Tissue

“…One promising therapeutic approach is the application of low-frequency, low-intensity ultrasound (LFLI US), which has been shown in clinical trials to significantly accelerate wound healing of chronic VLUs [7][8][9][10]. In a double-blind study, patients with VLUs were treated with a nonoperational sham device or with LFLI US operating at 20 kHz and 100 mW/cm 2 once a week for 15 minutes or 45 minutes for 8 weeks [8].…”

Evaluation of the effectiveness of combination ultrasound treatment and basic care in the healing of pressure ulcers: A Systematic Review

“…10,18,19 The LFUS wound debridement offers a less traumatic, less painful surgical debridement, achieving destruction of the bacterial biomembrane, removing necrotic tissues, fibrosis, exudate and accelerating the formation of granulation tissue. [20][21][22] The LFUS waves act through two mechanisms: microcavitation and acoustic flow. Cavitation leads to cellular changes, destruction of periwound tissue in the ultrasound wave, also causes a rapid lysis of the necrotic tissue and ulceration fibrosis.…”

“…The acoustic flow increases cell permeability and activates the intracellular secondary transport system which in turn causes an increase in collagen synthesis and production, growth factors, increase angiogenesis, macrophage response and fibrinolysis. 9,10,18,22…”

Cavitation-Enhanced Delivery of the Nanomaterial Graphene Oxide-Doxorubicin to Hepatic Tumors in Nude Mice Using 20 kHz Low-Frequency Ultrasound and Microbubbles

“…One characteristic of low-frequency (20-100 kHz [35]) ultrasound (US) is the cavitation effect [36]. The cavitation effect refers to the periodic oscillation of microbubbles (MBs) under the action of the US field [37].…”