Pathological-microenvironment responsive injectable GelMA hydrogel with visualized biodegradation for pressure-assisted treatment of hypertrophic scars.

Intralesional injection of 5-fluorouracil for the clinical treatment of hypertrophic scars (HS) remains challenging due to its short half-life, as well as the absence of evidence-based dosage and frequency injection guidelines. Herein, we developed a matrix metalloproteinases (MMPs)/reactive oxygen species (ROS)-responsive injectable prodrug hydrogel (GFP) that exhibits sustained drug release and fluorescence imaging capability, aiming to facilitate the optimization of injection dosage and frequency in HS treatment. The GFP hydrogel comprises gelatin methacryloyl and pendant methacryloyl-decorated tetrapeptide (PPPK) with 5-fluorouracil acetic acid/rhodamine B at the N-terminus. After intralesional injection and blue light irradiation, the crosslinked hydrogel in HS lesions exhibited long-term sustained drug release by consuming overexpressed MMPs and ROS, which could be visualized by fluorescence imaging to guide injection frequency for HS treatment. In addition, due to its exceptional swelling and mechanical properties, the GFP hydrogel exerts a certain pressure inside the HS tissues, functioning as an adjunctive therapy to inhibit HS. Our results demonstrate that the GFP hydrogel can promote fibroblast apoptosis, inhibit collagen synthesis, and remodel the microenvironment of HS. This study presents a promising visualized drug delivery platform that potentially guides the optimization of injection frequency and dosage in the treatment of HS.