Clinical translation of polymeric microneedles for bioactive nanovesicle delivery in hypertrophic scar remodeling.

The clinical translation of polymeric microneedle (MN)-based delivery systems for fibrotic diseases remains largely unexplored despite extensive preclinical advances. The dense extracellular matrix of pathological scars constitutes a formidable biophysical barrier that limits homogeneous macromolecular permeation. Here, we conducted a prospective, single-center, open-label, single-arm study evaluating a 12-week protocol combining microplasma radiofrequency (RF), poly(L-lactic acid) (PLLA) MNs, and topical milk-derived bioactive nanovesicles (mBNVs) in 26 patients with hypertrophic scars. Clinical scales and multimodal imaging were used to assess treatment-associated changes. At week 12, the combined protocol was associated with reductions in VSS and POSAS Patient Scale scores, scar stiffness and thickness, and dermoscopic vascular and pigmentation densities. MN-induced microchannels underwent rapid closure, treatment-related reactions were mild and transient, and no serious or systemic adverse events were observed. Collectively, these findings support the short-term feasibility, tolerability, and preliminary clinical activity of the combined protocol, offering a safe and non-steroidal paradigm for mechanically resistant pathological tissues.