Biological scaffolds are widely utilized in hernia treatment due to their exceptional pro-regenerative properties, which mitigate scar formation. However, serious complications occurred, caused by inflammatory response, premature degradation, and mechanical failure. Consequently, improvements of the biological scaffold are necessary to mitigate these risks. In this study, a novel biological scaffold integrating basement membrane-containing urinary bladder matrix (UBM) and small intestinal submucosa (SIS) is developed, and its safety and effectiveness are assessed in comparison to a commercial SIS (c-SIS) scaffold. The introduction of UBM as top surface layers significantly promotes cell adhesion, facilitating rapid formation of isolated regeneration zone. Proteomic analysis has demonstrated a more efficientdecellularization of the UBM/SIS scaffold, which subsequently mitigates inflammation in murine models, and promotes the polarization of macrophages toward the pro-healing M2 phenotype in a rat model of abdominal wall muscle defect. Furthermore, a two-year repair trial is conducted on a full-thickness abdominal wall muscle defect in canine model and confirmed that the UBM/SIS scaffold exhibits reduced seroma occurrences and enhanced tissue repair performances. Overall, the efficacyof this novel biological scaffold suggests its potential to minimize hernia recurrence in clinical practice and mitigatepatient suffering from severe inflammatory responses.
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