D-RADA16 self-assembling peptide microneedle patches alleviate osteoarthritis inflammation by inhibiting mtDNA...

Mitochondrial DNA (mtDNA) leakage and its activated cGAS-STING signaling pathway play a critical role in chronic inflammation of osteoarthritis (OA). However, how to effectively suppress mtDNA leakage and maintain joint homeostasis remains a huge challenge. This study proposes a synergistic strategy that combines the bioactive, extracellular matrix (ECM)-mimicking properties of D-RADA16 self-assembling peptides with the minimally invasive, localized delivery capabilities of a dissolvable microneedle patch (MNP). The resulting D-RADA16@MNP system forms a nanofibrous ECM-like microenvironment that promotes mitochondrial stability, limits mtDNA leakage, and modulates cGAS-STING-mediated inflammation. Compared with conventional intra-articular injections or NSAID therapy, D-RADA16@MNP enables precise, sustained, and patient-friendly transdermal delivery to inflamed joints. This synergistic interaction between the ECM-mimicking scaffold and the transdermal microneedle platform gives rise to a localized "cell safe-house" effect, which stabilizes the mitochondrial microenvironment, reduces mtDNA leakage, and suppresses inflammatory signaling. This study not only expands the biomedical application of D-form self-assembling peptides, but also provides a promising direction for the treatment of chronic inflammatory joint diseases.