Comparative in vitro and in vivo assessment of three experimental extracellular matrix meshes for soft tissue remodeling.

The development of standardized cross-species evaluation frameworks is urgently needed for absorbable extracellular matrix (ECM) meshes, due to significant variations in safety and efficacy across tissue sources. This study establishes a multi-dimensional assessment system to quantify material-specific bio-functional correlations. Three ECM meshes-human acellular dermis (HAD), porcine acellular dermis (PAD), and porcine small intestinal submucosa (SIS)-were systematically characterized using integrated in vitro and in vivo analyses. Assessments included physicochemical properties (e.g., degradation kinetics via collagenase digestion), immunogenic residues (α-Gal epitopes and DNA quantification), and biocompatibility. In vivo performance was evaluated using rabbit subcutaneous (for degradation and immune response) and rat abdominal defect models (for macrophage polarization: CD206⁺/CD86⁺ ratio and collagen deposition). HAD exhibited superior structural stability (82.3% ± 1.2% residual mass after 7-day collagenase digestion), whereas SIS degraded most rapidly (10.5% ± 0.42%; p < 0.01 vs PAD) but provoked severe foreign body reactions (2.3-fold higher vs HAD at 13 weeks, p = 0.017). Notably, HAD uniquely promoted sustained M2-dominant macrophage polarization (CD206⁺/CD86⁺ ratio = 2.1 vs SIS = 0.7), which reduced inflammation and enhanced collagen remodeling (p < 0.05 vs SIS). Serum metabolomic analysis indicated that ECM mesh implantation induced a reprogramming of host amino acid metabolism, marked by a notable acceleration in L-methionine metabolism. The proposed integrated evaluation framework successfully identifies material-specific correlations among degradation behavior, immune response, and metabolic regulation, providing critical benchmarks for the rational design of immunomodulatory ECM meshes.