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Tree thorns-inspired hyaluronic acid-based dissolving microneedles loaded with salvianolic acid B for effective hypertrophic scar treatment with enhanced long-term stability

Bricard Mbituyimana,Longjun Luo,Fuyu Qi,Yuchi Jiang,Omar Mohammad Atta,Mohamed S. Kishta,Mostafa Maboruk,Min Wu,Wei Ge,Zhijun Shi,Guang Yang

Hypertrophic scar (HS) represents a natural consequence of abnormal fibroproliferation occurring during wound healing, which not only leads to tissue dysfunction but also causes psychological issues for patients. Up to now, no completely effective therapy for HS has been found. Salvianolic acid B (Sal B), one of the natural plant-derived compounds, has the capacity to suppress the fibrosis process in scarring treatment. Nevertheless, due to its poor skin-penetration ability and unsatisfactory stability in existing formulations, its current clinical applicability is restricted. In this study, inspired by the separation behavior of the thorns on the trunks of the silk floss tree, we developed a hyaluronic acid (HA) dissolving microneedle (MN) platform loaded with Sal B. This platform can enhance the sustainable delivery of Sal-B directly into scar tissue in a minimally invasive manner, thereby enhancing the efficacy of HS therapy and improving the stability of Sal B. To evaluate the therapeutic efficacy of Sal-B MN, we established a rabbit ear HS model. After being administered five times, Sal-B MN significantly reduced the scar elevation index (SEI) and down-regulated the expressions of collagen I, transforming growth factor beta 1 (TGF-β1), Signal Transducer and Activator of Transcription 3 (STAT3), and alpha-smooth muscle actin (α-SMA). Notably, these effects were still evident even after six months of storage at room temperature. This indicates that tree-inspired Sal-B MN holds great potential as a highly effective tool for HS treatment with a long shelf-life. This makes the system suitable for clinical application and storage under various conditions.