This research was supported by the Domestic Medical Device Clinical Trial subsidies of the Korea Health Industry Development Institute, Seoul, Republic of Korea.
This work was presented as a poster at the 2018 European Wound Management Association Conference in Kraków, Poland.
Debridement is a crucial process in wound care. Low-frequency ultrasound debridement is a relatively painless modality that eliminates necrotic tissue, decreases bacterial counts, and minimizes blood loss. ULSC-12D is a lightweight and compact ultrasound surgery system, and SONOCA 180 is a larger conventional system. We compared the efficacy and safety of these two devices in a multicenter randomized controlled clinical trial and conducted relevant
Thirty patients were enrolled in the clinical trial and randomly allocated to two groups: the study group undergoing debridement using ULSC-12D and the control group undergoing debridement using SONOCA 180. Intra-procedural pain and post-procedural reduction of bacteria and necrotic tissue were evaluated. Experimental
There were no significant differences in outcome between two clinical trial groups. Both devices provided acceptable necrotic tissue and bacterial reduction, and no significant adverse events were reported. In
ULSC-12D is as effective and safe as the more conventional SONOCA 180 for wound debridement and yields superior results to SONOCA 180 in
Chronic wounds have a profound effect on both patients and medical systems. In the United States, it is estimated that chronic wounds affect 6.5 million patients and cost the medical system over US $25 billion annually [
Debridement, or removal of non-viable tissue to expose healthy, perfused tissue, is a crucial process in chronic wound care. Necrotic debris acts as a reservoir for infection and impedes wound healing, and thus must be removed in all cases. Debridement can be performed using a variety of techniques, including both autolytic and surgical mechanisms. The optimal timing and frequency of surgical debridement should be tailored to each wound.
Ultrasonic therapy is a relatively painless debridement modality that uses sound waves with a frequency at or above 20 kHz. It preferentially eliminates necrotic tissue, decreases bacterial counts, and minimizes blood loss [
Two current devices for low-frequency ultrasonic therapy are ULSC-12D and SONOCA 180. ULSC-12D is a lightweight and compact ultrasound surgery system lending itself to portable uses (
We compared the efficacy and safety of ULSC-12D with the conventional SONOCA 180 system in a multicenter randomized controlled clinical trial. We also performed
A multicenter, randomized, controlled study was carried out with two groups: the study group undergoing debridement using ULSC-12D (Ul-tech, Uiwang, Korea) and the control group undergoing debridement using SONOCA 180 (Söring, Quickborn, Germany). It was conducted at three medical institutes from February to November 2013. A total of 30 patients with pressure ulcers were recruited and enrolled according to the inclusion and exclusion criteria (
All the patients were evaluated for intra-procedural pain and post-procedural reduction of bacterial load and necrotic tissue. The procedures were done without anesthesia. Pain was assessed on a visual analog scale. Both bacterial load and the extent of necrotic tissue were measured before and 30 minutes after debridement. Bacterial load was measured using 5×5 cm nitrocellulose membrane filters gently pressed to the center of the wound and immediately inserted into a Columbia Blood Agar plate. Bacterial load was measured by counting the number of individual colonies on the plates after incubating at 37°C for 16 hours. The extent of necrotic tissue was measured using OpSite Flexigrid and Visitrak (Smith and Nephew, London, UK).
The clinical trial was approved by the institutional review board and ethics committee of Seoul National University Bundang Hospital, Samsung Medical Center, and Hanyang University Hospital. It was registered at ClinicalTrials.gov (Identifier: NCT02007824). Informed consent was obtained for all patients.
Human skin fibroblast culture was established using explants from the dermis of adult foreskin. Fibroblasts were cultured in complete Dulbecco’s modified Eagle’s medium supplemented with 10% fetal bovine serum (FBS), 2 mM L-glutamine (Sigma Chemical Company, Saint Louis, MO, USA), and 1X Antibiotic-Antimycotic (Gibco Life Technologies, Grand Island, NY, USA). The cells were subcultured when approximately 90% confluent. Primary endothelial cells were obtained from human umbilical veins, subcultured, and maintained in a 0.2% w/v gelatin-coated 25 cm2 culture flask with complete McCoy’s 5A medium (Flow Laboratories, McLean, VA, USA) supplemented with 20% FBS, 50 mg/mL endothelial cell growth supplement (Collaborative Research, Bedford, MA, USA), and 100 mg/mL heparin (Sigma Chemical Company) until reaching confluence, within 4 to 5 days. Endothelial cells were seeded in a 6-well plate coated with 0.2% w/v gelatin. Cells were cultured in a humidified incubator at 37°C and 5% CO2 and used at passages 3 to 6 for all experiments. For all
The WST-8 cell proliferation assay was performed on each fibroblast group. When reduced by intracellular dehydrogenase, water-soluble WST-8 [2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium sodium salt] forms a yellowish product (formazan), which is used to measure the number of viable cells.
Collagen synthesis was measured by an immunofluorescence technique using a monoclonal anti-collagen antibody. The anti-collagen antibody was obtained by immunizing mouse splenocytes with human collagen. The anti-collagen antibody was labeled with a fluorescent marker and collagen synthesis was measured in each group of human fibroblasts after ultrasound exposure.
Growth factor expression was measured by reverse transcription polymerase chain reaction. Expression levels of basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), and granulocyte macrophage colony stimulating factor (GM-CSF) were measured in each group of cultured fibroblasts after exposure to each device.
Nitric oxide is a highly reactive free radical gas and oxidizer, which remains stored in tissues as nitrate or nitrite. A colorimetric Griess reaction was used to quantify the combined concentration of nitrate and nitrite. Quantitative analysis of nitric oxide production was performed in each endothelial cell group after ultrasound exposure.
The mean and standard deviation (SD) for each set of measurements was calculated. The results were analyzed using one-sample t-tests and one-way analysis of variance. Results were considered significant if the significance level (P-value) was lower than 0.05.
The reduction in bacterial counts after debridement was 96.3%±6.7% (mean±SD) in patients treated with ULSC-12D, and 91.6%±16.2% in patients treated with SONOCA 180. The extent of the necrotic tissue was reduced 27.1%±8.1% (mean± SD) post-debridement with ULSC-12D, and 15.1%± 18.2% with SONOCA 180. The differences between groups did not reach statistical significance, however there was a trend toward improved outcomes using ULSC-12D. The average intra-procedural pain assessment score was 5.4 in the ULSC-12D group, and 4.8 in the SONOCA 180 group. This difference was also statistically insignificant, suggesting both devices have comparable efficacy. No significant adverse event was reported in either group during the study (
The proliferation rate of fibroblasts was 122.48%±7.11% (mean±SD) in the ULSC-12D group, 110.38%±2.46% in the SONOCA 180 group, and 98.23%±2.47% in the control group. The groups treated with ultrasound were significantly more proliferative than the control group, but the difference between the two ultrasound treatment modality groups was not significant. The collagen synthesis of fibroblasts was 14.53±1.94 μg/mL (mean±SD) in the ULSC-12D group, 6.23±1.48 μg/mL in the SONOCA 180 group, and 1.53±0.22 μg/mL in the control group. The ULSC-12D-treated fibroblasts showed significantly higher collagen production than the other two groups. Expression of bFGF also increased significantly in ULSC-12D group, but there was no significant change in the expression of PDGF or GM-CSF or any growth factors tested in other groups.
Nitric oxide production of endothelial cells was 3.90±0.63 μM (mean±SD) in the ULSC-12D group, 3.32±0.27 μM in the SONOCA 180 group and 2.65±0.25 μM in the control group. Ultrasound treatment significantly enhanced nitric oxide production by epithelial cells compared to the control group, and the effects of ULSC-12D and SONOCA 180 were equivalent (
ULSC-12D is as effective and safe as the more conventional SONOCA 180 for wound debridement. Both devices provided acceptable necrotic tissue and bacterial reduction, and no significant adverse events were reported. In
Ultrasound is a type of sound wave with a frequency greater than 20 kHz, which is out of the range of human hearing. It is widely used not only for diagnostic, but also for therapeutic purposes. Therapeutic ultrasonic devices can be classified by frequency. Low-frequency devices generate ultrasound ranging between 20 and 60 kHz. High-frequency devices mainly function through the thermal and mechanical effects that occur as tissue absorbs ultrasound. Heat promotes wound healing by promoting blood flow to the tissue [
Therapeutic ultrasound at an appropriate dosage has been reported to induce cell proliferation, protein synthesis, and cytokine production by fibroblasts, osteoblasts, and monocytes [
Nitric oxide is a soluble gas continuously synthesized in endothelial cells. It has a wide range of biological properties including modulation of vascular tone [
The prevention and treatment of wound infection are important concerns in wound management. There are several reports suggesting that therapeutic ultrasound suppresses wound infection. A reduction in bacterial load of diverse bacteria was demonstrated by
In conclusion, we have conducted a comparative clinical trial between two ultrasonic surgery systems and performed relevant
No potential conflicts of interest relevant to this article are reported.
ULSC-12D (investigational device).
SONOCA 180 (control device).
Growth factor expression. Expression of basic fibroblast growth factor (bFGF) increased significantly in ULSC-12D group, but there was no significant change in the expression of platelet-derived growth factor (PDGF) or granulocyte macrophage colony stimulating factor (GM-CSF) or any growth factors tested in other groups. GAPDH, glyceraldehyde 3-phosphate dehydrogenase.
Inclusion and exclusion criteria
Inclusion criteria | Exclusion criteria |
---|---|
Patients aged 20 or older | Patients with signs of cellulitis |
Patients with at least 3 cm² of pressure ulcer area | Patients with comorbidities hindering proper assessment included in the study |
Patients with a stage 2 or greater pressure ulcer requiring debridement | Patients with wounds treated in 2 weeks except simple dressing changes |
Clinical outcomes
ULSC-12D group | SONOCA 180 group | |
---|---|---|
Bacterial reduction rate | 96.3±6.7 | 91.6±16.2 |
Necrotic area reduction rate | 27.1±8.1 | 15.1±18.2 |
Pain |
5.4 | 4.8 |
Values are presented as mean±SD. There was no statistical difference in any category.
The pain assessment score is 0 (no pain) to 10 (maximum pain).
Experimental
ULSC-12D group | SONOCA 180 group | Control group | ||
---|---|---|---|---|
Fibroblast | Proliferation rate | 122.48±7.11 | 110.38±2.46 | 98.23±2.47 |
Collagen synthesis (μg/mL) | 14.53±1.94 |
6.23±1.48 | 1.53±0.22 | |
Endothelial cell | Nitric oxide production (μM) | 3.90±0.63 | 3.32±0.27 | 2.65±0.25 |
Values are presented as mean±SD. All values were statistically different from the control group (P<0.05).
P<0.05 statistically different from SONOCA 180 group.