Effect of Cross-Linked and Non-Cross-Linked Acellular Dermal Matrices on the Expression of Mediators Involved in Wound Healing and Matrix Remodeling

1Department of General Surgery, Tripler Army Medical Center, Honolulu, Hawaii, USA 2Department of Clinical Investigation, Tripler Army Medical Center, Honolulu, Hawaii, USA.
Plastic and Reconstructive Surgery (Impact Factor: 3.33). 12/2012; 131(4). DOI: 10.1097/PRS.0b013e3182818a3d
Source: PubMed

ABSTRACT BACKGROUND:: Molecular mechanisms that direct the extent of the foreign body reaction to implanted biologic meshes and their subsequent incorporation are poorly understood. The purpose of this study was to compare the influence of non-crosslinked human dermis (Alloderm) versus crosslinked porcine dermis (Permacol) 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 with Alloderm, Permacol, or suture repair with no mesh (n=10 rats per group). Explants were harvested 90 days after repair and divided for histological, immunohistochemical, and gene expression analyses. Real-time quantitative polymerase chain reaction arrays were used to profile the expression of 84 wound healing-associated genes at the tissue-mesh interface. RESULTS:: Both meshes induced the differential expression (≥3-fold change relative to suture repair, p≤0.01) of extracellular matrix components, remodeling enzymes, and inflammatory cytokines. Genes most markedly upregulated included matrix metalloproteinase (MMP) 9 (66-fold, Permacol; 19-fold, Alloderm) and chemokine (C-C motif) ligand 12 (CCL12, 24-fold, Permacol; 71-fold, Alloderm). Immunohistochemistry using antibodies against MMP9 and CCL12 confirmed differential expression at the protein level (p<0.001). Histologically Alloderm demonstrated overall better remodeling characteristics than Permacol. CONCLUSIONS:: Permacol elicits increased protease expression and reduced cellular and vascular infiltration compared to Alloderm 90 days after implantation, indicative of delayed remodeling induced by crosslinking. 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. LEVEL OF EVIDENCE:: N/A (animal study).

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