Characterization of Physicochemical, Biocompatible Properties and Investigation on Repair Mechanism of Three Typical ECM Meshes in Vitro and in Vivo

BACKGROUND Absorbable extracellular matrix (ECM) meshes lack standardized evaluation frameworks for cross-species safety and efficacy. This study aimed to establish a comprehensive assessment system for clinical-grade ECM meshes. METHODS Three ECM meshes—human/pig dermis (HAD/PAD) and porcine small intestinal submucosa (SIS)—were characterized for physicochemical properties and biocompatibility. In vitro degradation was tested via collagenase digestion. Immunogenic residues (α-gal antigen, DNA) were quantified. In vivo performance was evaluated in rabbit subcutaneous and rat abdominal wall defect models, analyzing degradation, immune response, macrophage polarization (CD206 + M2), and collagen deposition. RESULTS SIS showed rapid in vitro degradation (90.49 ± 0.42% mass loss by day 7, fourfold faster than PAD, p  < 0.01). HAD induced minimal foreign body reactions (2.3-fold weaker than SIS at day 30, p = 0.017) and sustained M2 dominance (68.4% vs. 41.2% in SIS). Serum metabolomics revealed ECM-specific amino acid metabolic shifts. Rat models confirmed reduced inflammation and enhanced collagen remodeling with HAD/PAD vs. SIS. CONCLUSION This integrated evaluation framework identifies material-specific degradation-immune correlations, providing benchmarks for immunomodulatory ECM scaffold design.