Mechanical stretch is utilized in the process of tissue expansion to promote skin regeneration, which is crucial for wound healing and organ reconstruction purposes. Enlarged dermal area is one of the significant histological characteristics of the expanded skin. However, the underlying biological processes and molecular pathways associated with dermal regeneration triggered by mechanical stretch are still not well understood. Twelve male Sprague-Dawley (SD) rats were divided into the expansion group and sham group randomly. Upon creating a rat scalp expansion model, the dermis was isolated from the full-thickness skin in both experimental groups for RNA sequencing. This process led to the identification of differentially expressed genes (DEGs). Subsequently, we conducted Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Gene Set Enrichment Analysis (GSEA) to identify the essential biological processes associated with dermal regeneration induced by mechanical stretch, leveraging data from the DEGs. A network of protein-protein interactions (PPI) was built to detect the critical modules and central genes. The expression levels of these hub genes were evaluated using quantitative real-time polymerase chain reaction (qPCR). Increased expanded skin area and dermal thinning which represent the typical changes of expanded skin were observed in the expansion group. A total of 782 DEGs were identified in the expansion group relative to the sham group. The DEGs were associated with several biological processes, including the organization of the extracellular matrix, the enhancement of macrophage activation, and the promotion of angiogenesis, among others. Cell components encompassing Toll-like receptor 2-Toll-like receptor 6 protein complex, interstitial matrix, extracellular matrix (ECM), and collagen trimer were discovered. Molecular function categories including integrin binding, insulin-like growth factor binding, and fatty acid elongase activity were involved. The KEGG pathway analysis demonstrated the significant enrichment of pathways including the PI3K-Akt signaling pathway, fatty acid metabolism, and extracellular matrix-receptor interactions. GSEA results displayed that mechanical stretch correlated with the regulation of cell activation processes, cytokine-mediated signaling pathways, and immune system processes. PPI network resulted in the identification of 598 nodes along with a total of 5,304 interaction pairs between proteins. And ten hub genes containing Ccl2, Cxcl10, Fasn, Itgad, Cd163, Mmp9, Cd36, Tlr2, Igf1, and Wnt2 were identified by bioinformatics analysis and validated by qPCR. This in vivo study for the first time revealed the DEGs related to mechanical stretch stimulated dermal regeneration and identified the involved pathways and hub genes correlated with macrophage recruitment and polarization, fibroblast proliferation and ECM production and angiogenesis, which may benefit further studies aimed at developing therapeutic strategies for facilitating expanded skin regeneration.

Purpose: Divided eyelid nevi pose significant challenges for affected individuals. Traditional surgical options often result in a suboptimal color or texture match. This study evaluates the outcomes of using an expanded forehead flap for the reconstruction of these complex defects. Methods: Between 2013 and 2024, 7 patients with divided eyelid nevi underwent staged reconstruction with an expanded forehead flap. The surgical technique involved 3 stages: (1) insertion and inflation of a tissue expander in the supraeyebrow region; (2) transfer of the expanded flap to the periorbital defect following lesion excision, with the flap pedicled on the supratrochlear artery; and (3) 3 weeks postoperatively, axial vessel ligation was performed for flap delay, followed by pedicle division and defect repair 1 week later. Clinical data, surgical details, and outcomes were recorded and analyzed. Results: All 7 flaps survived completely. Flap sizes ranged from 3.0×3.0 to 10.0×10.0 cm. Minor complications included 1 case of wound dehiscence near the expander port, which healed with conservative management. No cases of flap necrosis, venous congestion, brow ptosis, or ectropion were observed. The color, texture, and thickness of the flaps showed an excellent match with the recipient site. One patient underwent subsequent flap thinning for perceived bulkiness. During a follow-up period of 3 to 24 months, all patients expressed satisfaction with both the aesthetic and functional outcomes. Conclusions: The expanded forehead flap based on the supratrochlear and supraorbital vessels is a reliable and effective technique for reconstructing divided eyelid nevi.