Antibiotic-loaded PMMA Bone Cement Promotes Diabetic Wound Healing via Induced Membrane Formation: A Transcriptomic and Mechanistic Study

DFU is a prevalent complication among diabetic patients, significantly impairing their quality of life.PMMA-induced membrane therapy has gained increasing attention as a specialized healing tissue closely linked to bone regeneration. This study aims to explore the impact of PMMA-induced membrane therapy on the transcriptome of DFU tissues. We conducted RNA-seq, WGCNA and machine learning techniques on human DFU tissue samples to identify DEGs associated with induced membrane formation and function, analyzing their potential roles in the healing process. Gene expression analysis enabled the construction of a gene co-expression network, revealing 18 distinct modules. Among these, the turquoise module exhibited the strongest correlation with induced membrane formation. By intersecting induced membrane-related genes with DEGs across different conditions, we identified 422 overlapping genes. Functional enrichment analysis indicated that these genes are primarily involved in the citric acid cycle, respiratory electron transport, and ATP synthesis via chemiosmotic mechanisms. PPI network analysis further validated key gene interactions within the induced membrane. Using machine learning approaches—including Random Forest, LASSO regression, and SVM-RFE—we identified four potential biomarker genes: ATP5F1D, SNRPD2, RPL26, and NOC4L.Our findings underscore the critical role of the induced membrane in DFU healing and uncover its potential molecular mechanisms.