Time- and Dose-Dependent Effects of Pulsed Ultrasound on Dermal Repair in Diabetic Mice

Ultrasound Med Biol. 2021 Apr;47(4):1054-1066. doi: 10.1016/j.ultrasmedbio.2020.12.024. Epub 2021 Jan 13.

Abstract

Chronic wounds, including diabetic, leg and pressure ulcers, impose a significant health care burden worldwide. Some evidence indicates that ultrasound can enhance soft tissue repair. However, therapeutic responses vary among individuals, thereby limiting clinical translation. Here, effects of pulsed ultrasound on dermal wound healing were assessed using a murine model of chronic, diabetic wounds. An ultrasound exposure system was developed to provide daily ultrasound exposures to full-thickness, excisional wounds in genetically diabetic mice. Wounds were exposed to 1 MHz ultrasound (2 ms pulse, 100 Hz pulse repetition frequency, 0-0.4 MPa) for 2 or 3 wk. Granulation tissue thickness and wound re-epithelialization increased as a function of increasing ultrasound pressure amplitude. At 2 wk after injury, significant increases in granulation tissue thickness and epithelial ingrowth were observed in response to 1 MHz pulsed ultrasound at 0.4 MPa. Wounds exposed to 0.4 MPa ultrasound for 3 wk were characterized by collagen-dense, revascularized granulation tissue with a fully restored, mature epithelium. Of note, only half of wounds exposed to 0.4 MPa ultrasound showed significant granulation tissue deposition after 2 wk of treatment. Thus, the db+/db+ mouse model may help to identify biological variables that influence individual responses to pulsed ultrasound and accelerate clinical translation.

Keywords: Chronic diabetic wounds; Therapeutic ultrasound; Tissue regeneration; Wound healing.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chronic Disease
  • Collagen / metabolism
  • Diabetes Complications / therapy*
  • Disease Models, Animal
  • Filaggrin Proteins
  • Granulation Tissue / blood supply
  • Granulation Tissue / pathology
  • Granulation Tissue / radiation effects*
  • Intermediate Filament Proteins / metabolism
  • Male
  • Mice
  • Neovascularization, Physiologic
  • Random Allocation
  • Re-Epithelialization / radiation effects*
  • Skin / injuries*
  • Skin / pathology
  • Ultrasonic Therapy*
  • Ultrasonic Waves
  • Wounds and Injuries / metabolism
  • Wounds and Injuries / pathology
  • Wounds and Injuries / therapy*

Substances

  • Filaggrin Proteins
  • Intermediate Filament Proteins
  • Collagen