Angiogenesis-facilitating and inflammation-modulating SIS-based patches coupled with functional peptides for abdominal wall repair

Abdominal wall defects caused by trauma, tumors, infections, abdominal surgery, and congenital factors can lead to functional impairments. The use of patches remains the most effective treatment approach. However, current repair materials still have limitations in regulating inflammation and promoting vascularization. Here, a small intestinal submucosa (SIS) extracellular patch was developed via conjugation with functional peptides PR1P and LL37 (<i>i.e.</i>, SIS-PR1P-LL37), to achieve angiogenesis and inflammation modulation for abdominal wall repair. In vitro experiments confirmed its superior pro-angiogenic potential when human umbilical vein endothelial cells (HUVECs) were treated with the patch, both tube formation (total tube length: 4.51 ± 0.53 mm, junction count: 28.00 ± 4.97) and scratch wound repair (repair area 3.26-fold that of the SIS group) outperformed the native SIS group (average tube length: ∼1.3 mm). After 7 days of culture, the VEGF expression was higher than that in the SIS group, and the expression levels of key angiogenic genes (VEGF, VEGFR-2, <i>etc.</i>) were 5.45-7.82-fold higher than those in the control group. Additionally, this peptide-conjugated SIS patch could enhance cell proliferation and angiogenic differentiation, effectively reduce the levels of inflammatory cytokines, and enrich the TLR and VEGF signaling pathways. The rat abdominal wall defect model further confirmed its superior capacity for tissue regeneration and angiogenesis, indicating it provides important theoretical and experimental support for the development of novel bioactive patches and holding promise for optimizing clinical strategies for abdominal wall repair.