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

Carlson, Terri L. D.O.; Lee, Karen W. B.S.; Pierce, Lisa M. D.Sc.

Plastic and Reconstructive Surgery: April 2013 - Volume 131 - Issue 4 - p 697–705
doi: 10.1097/PRS.0b013e3182818a3d
Experimental: Original Articles

Background: Molecular mechanisms that direct the extent of the foreign body reaction to implanted biological meshes and their subsequent incorporation are poorly understood. The purpose of this study was to compare the influence of non–cross-linked human dermis (AlloDerm) with that of cross-linked 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 histologic, 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 up-regulated included matrix metalloproteinase-9 (Permacol, 66-fold; AlloDerm, 19-fold) and chemokine (C-C motif) ligand 12 (Permacol, 24-fold; AlloDerm, 71-fold). Immunohistochemistry using antibodies against matrix metalloproteinase-9 and chemokine (C-C motif) ligand 12 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 with 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.

Honolulu, Hawaii

From the Departments of General Surgery and Clinical Investigation, Tripler Army Medical Center.

Received for publication September 12, 2012; accepted October 8, 2012.

Presented at Plastic Surgery The Meeting 2012, the 81st Annual Meeting of the American Society of Plastic Surgeons, in New Orleans, Louisiana, October 26 through 30, 2012.

Disclaimer: The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Army, Department of Defense, or the U.S. government.

Disclosure: The authors have no commercial associations or financial relationships that would create a conflict of interest with the work presented in this article.

Lisa M. Pierce, D.Sc.; Department of Clinical Investigation, Tripler Army Medical Center, 1 Jarrett White Road, Honolulu, Hawaii 96859-5000,

©2013American Society of Plastic Surgeons