Influence of Acellular Dermal Matrices On the Expression of Mediators Involved In Wound Healing and Tissue Remodeling

Purpose:  Biologic meshes for abdominal wall and breast reconstruction have been introduced recently in an effort to create a graft that demonstrates improved integration into host tissue and resistance to infection compared to synthetics.¹ The theoretical advantage of biologic over synthetic materials is that they function as regenerative scaffolds which become remodeled into native host tissue. The ideal biologic implant resists infection, allows for remodeling, and provides strength to surrounding structures; nevertheless, no biologic material currently available has demonstrated optimal biocompatibility.  Molecular mechanisms that direct the extent of the foreign body reaction to implanted biologics and their subsequent incorporation are poorly understood.  We therefore compared the influence of two commonly used biologic meshes on the expression of genes critical for wound healing and tissue remodeling in a rat ventral hernia model.

Methods:  Full thickness abdominal wall defects were repaired using non-cross-linked human dermis (Alloderm, LifeCell Inc.; n=10), cross-linked porcine dermis (Permacol, Covidien; n=10), or suture repair (no mesh; n=10).  Explants were harvested 90 days after repair and were divided for histological, immunohistochemical, and mRNA analyses.  Real-time quantitative PCR arrays were used to profile the expression of 84 wound healing-associated genes at the tissue-mesh interface.  

Results:  Both mesh types induced the differential expression (>2-fold change relative to suture repair, p≤0.01) of extracellular matrix components, remodeling enzymes, inflammatory cytokines, and growth factors (Permacol, 26 genes; Alloderm, 15 genes). Genes most markedly upregulated included matrix metalloproteinase (MMP) 9 (Permacol, 66-fold, p=0.02; Alloderm, 19-fold, p=0.01) and the monocyte chemoattractant CCL12 (Permacol, 24-fold, p<0.001; Alloderm, 71-fold, p=0.06).  Alloderm demonstrated overall better remodeling characteristics than Permacol, with increased cellular infiltration, extracellular matrix deposition, neovascularization, and scaffold degradation, but possessed similar scores for inflammatory cells.  Immunohistochemistry using antibodies against MMP9 confirmed differential expression at the protein level, with significantly increased expression in Permacol samples compared to Alloderm (p<0.001).

Conclusion:  Cross-linked porcine dermis (Permacol) elicits increased protease expression and reduced cellular and vascular infiltration compared to non-cross-linked human dermis (Alloderm) 90 days after implantation, indicative of delayed remodeling induced by cross-linking. Increased understanding of the host response to implanted materials ultimately will enable the development of improved meshes with enhanced wound healing properties and fewer graft-related complications.

1.  Rosen MJ. Biologic mesh for abdominal wall reconstruction: a critical appraisal. The American Surgeon 2010;76:1-6.