Synergistic Intervention of Piezo1 Activation and Fibrous Tissue Remodeling to Ease Side Effects of Intralesional Therapy for Keloids.

Abstract

Intralesional administration is the first-line therapy of keloids that can inhibit the growth of keloids and relieve patients' subjective symptoms. However, side effects, particularly pain, pose a significant challenge to injection therapy. A fractional ultrasound (FRUS) platform is developed to treat keloids and deliver drugs with minimal invasiveness and ease of operation. Keloid-bearing nude mice models are developed to investigate the in vivo effectiveness of FRUS. A pilot clinical trial is further undertaken to uncover its significancein clinical practice. This platform activated Piezo1 channels through low-frequency ultrasound, inhibiting fibroblast proliferation, and utilized the cavitation effect to remold fibrous tissues, improving drug diffusion, and finally alleviating side effects associated with injection therapy. In vivo mice experiments demonstrated that FRUS platform increased the expression of Piezo1 channels and inhibited keloids growth without causing systematic adverse events. Eight participants with keloids are enrolled in the clinical trial and treated with this approach combined with anti-keloid drugs. The findings indicated that FRUS significantly alleviated injection-associated pain by 51.9% and reduced the keloid volume. These results reveal the potential therapeutic mechanism and provide a foundation for the clinical application of this approach in enhancing keloids treatment.