ADSCC-CM-Induced Keratin Hydrogel-Based Bioactive Microneedle Patch Containing Triamcinolone Acetonide for the Treatment of Pathological Scar

Pathological scars (PS) are involved in the excessive response of inflammation and overactivation of myofibroblasts. Herein, a novel microneedle (MN) patch based on the adipose-derived stem cell concentrated conditioned medium (ADSCC-CM) cross-linked keratin hydrogel is developed to load triamcinolone acetonide (TA), thereby achieving the dual-drug delivery of ADSCC-CM and TA to simultaneously reduce the inflammation and guide myofibroblast behaviors. Results not only confirm the ability of ADSCC-CM to drive the formation of keratin-based hydrogel, but also verify the dual-drug release capacities of the hydrogel-developed MNs (TA@AC-MN). Using human hyperplastic scar fibroblast (HSF), the combination of ADSCC-CM and TA demonstrates a pronounced synergistic effect in mitigating the detrimental effects of the inflammatory microenvironment on HSFs, including suppressing the production of reactive oxygen species and attenuating the expression of inflammatory factors. Compared with the clinically used TA, TA@AC-MN promotes scar biomimetic repair (i.e., optimizing the proportion of collagen and increasing the tissue tensile strength). This study demonstrates that TA@AC-MN has the capacity to provide a self-managing and minimally invasive therapeutic strategy for PS.