A Randomized, Double-Blind, Split-Face, Clinical Trial of Angiopoietin-1 Derived Peptide Topical Following Fractional Radiofrequency Microneedling

September 2025 | Volume 24 | Issue 9 | 875 | Copyright © September 2025


Published online August 31, 2025

Catherine Di Giorgio MDa, Kaitlyn Ramsay PhDb*, Alaa Alsaafin PhDb,c*, Milica Radisic PhDb,c,d, Omar Ibrahimi MD PhDe

aCMD Dermatology, Laser & Aesthetics, Boston, MA, USA
bInstitute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada
cQuthero Inc, Miami, FL, USA
dDepartment of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, Canada
eConnecticut Skin Institute, Stamford, CT, USA

Abstract
Background: Energy-based devices are commonly used to improve the appearance of aging skin. Treatments can involve long recovery times, marked by pain, erythema, edema, and purpura, which is often a limiting factor in a patient’s willingness to undergo a procedure.
Objective: This study evaluated the safety and effectiveness of an Angiopoietin-1 derived QHREDGS peptide (Q-peptide) hydrogel and ointment, in comparison to a peptide-free control, in enhancing healing and patient satisfaction after radiofrequency microneedling (RFMN) treatment.
Methods: In this Institutional Review Board-approved, randomized, double-blind, split-face study, 8 subjects underwent RFMN. Post-procedure, they applied Q-peptide regimen to one side of their face and a peptide-free control to the other. Post-treatment recovery and skin quality were assessed at 2 ± 1 and 7 ± 1 days post-procedure. Adverse events were monitored.
Results: The Q-peptide regimen was preferred by both clinicians (6-fold) and subjects (5-fold) compared with the control at the first follow-up visit (2 ± 1 days). Subjects were 5-fold more likely to report better-looking skin and 5-fold more likely to report better-feeling skin on the Q-peptide side of the face. Image analysis demonstrated 2-fold decreased presence of edema, erythema, and purpura at 2 ± 1 days post-procedure. Improved skin quality and more rapid recovery were noted with the Q-peptide. By 7 ± 1 days, patients strongly favored Q-peptide, endorsing its continued use and recommending it to others. No adverse events were reported.
Conclusion: The Q-peptide regimen was effective and well-tolerated following RFMN treatment, highlighting its potential for skin regeneration and dermatological post-procedure use.

INTRODUCTION

Radiofrequency microneedling (RFMN) is a non-invasive skin rejuvenation technique that uses a needle array to deliver radiofrequency radiation to induce thermal injuries to the dermis. The process encourages the generation of new extracellular matrix (ECM) proteins, such as collagen and elastin. It can help diminish the appearance of fine lines, wrinkles, and acne scars. Long-pulsed fractional RFMN, however, entails a lengthy recovery time of a week or longer, accompanied by erythema, edema, and purpura, remaining a serious hindrance for many patients.

Topical therapies have shown benefits in reducing downtime and enhancing the healing process after dermatological procedures.1 The application of a topical solution containing antioxidants, anti-inflammatory drugs, and hyaluronic acid following fractional laser resurfacing significantly shortened the duration of erythema and increased skin hydration.2,3 Similarly, after RFMN, a topical mixture of all-trans-retinol, epidermal growth factor, and hyaluronic acid improved skin texture and overall skin quality.1

Angiopoietin-1 is a glycoprotein that interacts with the ECM, promotes cell survival and wound healing, protects from oxidative damage, and results in stable angiogenesis.4 Angiopoietin-1 also antagonizes actions of angiopoietin-2, which is known to associate with chronic inflammation, destabilization of blood vessels, and aging.5 We therefore hypothesized that developing a recovery regimen based on an angiopoietin-1-derived peptide and a suitable ECM component
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