Silencing siRNA microneedle patches versus silicone sheets in reducing post-surgical scars: a randomized single-blinded intra-individually controlled clinical trial.

Abstract

Background: A common complication of wounds is exuberant growth of fibrotic scar tissue, which can lead to hypertrophic scars or keloids. There are currently no treatments with good evidence for preventing excessive scar tissue formation. In this study, we explored the use of microneedle patches containing siRNA inhibiting SPARC mRNA in reducing the volume of post-surgical scars.

Objective: We aim to compare the differences in the volume of post-surgical scars between daily application of siRNA-embedded dissolving microneedle patches and silicone sheets. The primary study outcome measure was the 3D volume of scar elevation.Our hypothesis was that scar formation in the half of the wound treated with siRNA microneedle patches will be lesser, as reflected by a smaller 3D volume, as compared to the half treated with silicone sheets.

Methods: This was an 8-week, single-blinded intra-individually controlled randomised trial in a tertiary dermatological centre. Patients with two-week-old post-operative wounds were recruited. Each half of the scar was randomly assigned to the microneedle patch or silicone sheet. Three-dimensional (3D) volumes were obtained from the scars via a high-resolution scanner at day 0, 30 and 60.

Results: At day 30, scars treated with the microneedle patches had a lower geometric mean volume of 0.79mm3 when compared to scars treated with silicone sheets, with a difference in mean percentage volume reduction of 10.70%.At day 60, scars treated with the microneedle patches had a statistically significant lower volume (8.88mm3) when compared to the side treated with silicone sheets (12.77mm3, p=0.005), with a difference in mean percentage reduction of 9.66%. Additionally, there was also a statistically significant difference between the percentage reduction in scar volume, compared to baseline, on the side treated with microneedle patches (mean=83.78%) compared to the side treated with silicone sheets (mean=74.11%).

Conclusions: There was a significantly greater reduction in the volume of post-surgical scars on the side treated with microneedle patches compared to the side treated with silicone sheets. This demonstrates the use of transdermal gene silencing technology for scar inhibition and that siRNA microneedle patches can be an effective and safe modality in the reduction of scar tissue formation.

Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12622000558729, https://www.anzctr.org.au.