Hypertrophic scar is a fibrous hyperplastic disorder that arises from skin injuries. The current therapeutic modalities are constrained by the dense and rigid scar tissue which impedes effective drug delivery. Additionally, insufficient autophagic activity in fibroblasts hinders their apoptosis, leading to excessive matrix deposition. Here, we developed an active microneedle (MN) system to overcome these challenges by integrating micromotor-driven drug delivery with autophagy regulation to remodel the scar microenvironment. Specifically, sodium bicarbonate and citric acid were introduced into the MNs as a built-in engine to generate CO₂ bubbles, thereby enabling enhanced lateral and vertical drug diffusion into dense scar tissue. The system concurrently encapsulated curcumin (Cur), an autophagy activator, and triamcinolone acetonide (TA), synergistically inducing fibroblast apoptosis by upregulating autophagic activity. In vitro studies demonstrated that active MNs achieved efficient drug penetration within isolated scar tissue. The rabbit hypertrophic scar model revealed that TA-Cur MNs significantly reduced the scar elevation index, suppressed collagen I and transforming growth factor-β1 (TGF-β1) expression, and elevated LC3 protein levels. These findings highlight the potential of the active MN system as an efficacious platform for autonomous augmented drug delivery and autophagy-targeted therapy in fibrotic disorder treatments.

Objective:To investigate the germline mutation status in multi-pathway in Chinese female breast cancer patients and explore their correlation with clinicopathological characteristics. Aim to enrich the database of breast cancer germline gene mutations in Chinese population and provide laboratory evidence for the application of breast cancer targeted drugs.Methods:From January 2017 to July 2019, whole blood samples were collected from 148 women (age of onset concentrated in the 24~80 years old) diagnosed pathologically with breast cancer in the Department of breast surgery, Peking University People′s Hospital. Germline mutations in HR, MMR, BER, and KDR pathway related genes were detected by next-generation sequencing. The pathogenicity interpretation was performed, and pathogenic, likely pathogenic, and mutations of uncertain significance were screened. The clinicopathological characteristics including age at the onset, luminal typing, tumor size, metastasis, and family history were analyzed, and the correlation between mutations in different pathway genes and clinicopathological characteristics was analyzed by the Chi-squared test and Fisher′s exact probability test.Results:Among the 148 patients, there were 69 cases of HR mutations (including three types of mutations, including pathogenic, likely pathogenic and uncertain significance), 16 cases of MMR mutations, 6 cases of BER mutations and 8 cases of KDR mutation. ATM mutations in the HR pathway were associated with luminal typing ( P=0.054), and patients with HER2+breast cancer were more likely to carry ATM mutations. PMS2 mutations in the MMR pathway were correlated with tumor size ( P=0.060), and patients with tumor size>50 mm were more likely to carry PMS2 mutations. KDR mutations was significantly correlated with luminal typing and family history. ( P=0.021, P=0.024). Conclusion:The mutation frequency in BER, KDR, MMR and HR pathways in Chinese breast cancer patients increased successively. Germline mutations in ATM, PMS2 and KDR genes may be involved in the development of breast cancer in the Chinese population. Multi-pathway gene detection of breast cancer can provide laboratory evidence for the use of PARP inhibitors, trastuzumab and other targeted drugs.