Remodeling characteristics and biomechanical properties of a crosslinked versus a non-crosslinked porcine dermis scaffolds in a porcine model of ventral hernia repair

Abstract

Purpose The objective of this study was to evaluate the histologic remodeling profile and biomechanical properties of the porcine abdominal wall after repair with HDMI-crosslinked (Permacol®) or non-crosslinked (Strattice®) porcine dermis in a porcine model of ventral hernia repair. Methods Bilateral incisional hernias were created in Yucatan minipigs and repaired after 21 days. The repair site, including mesh and abdominal wall, was harvested after 1, 6, and 12 months and subjected to histologic analysis and uniaxial testing. Native abdominal wall without mesh was also subjected to uniaxial tensile testing. Results Permacol® demonstrated significant improvement over time in every remodeling category except scaffold degradation, while remodeling characteristics of Strattice® remained relatively unchanged over time for every category except fibrous encapsulation and neovascularization. However, remodeling scores for Strattice® were already significantly higher after just 1 month compared to Permacol® in the categories of cellular infiltration, ECM deposition, and neovascularization, providing evidence of earlier remodeling of the non-crosslinked grafts compared to the crosslinked grafts. The tensile strength and stiffness of both crosslinked and non-crosslinked graft-tissue composites were greater than the tensile strength and stiffness of the native porcine abdominal wall in the very early post-operative period (1 month), but there was no difference in tensile strength or stiffness by the end of the study period (12 months). Conclusions HDMI collagen crosslinking of porcine dermis scaffolds reduces the early histologic remodeling profile but does not significantly impact the tensile strength or stiffness of the graft-tissue composites in a porcine model of ventral hernia repair.

Biologic Scaffolds

“…However, because cross-linked ECM bioscaffolds are unable to degrade, their persistence in situ typically leads to a foreign body reaction (Anderson et al 2008) with the formation of connective tissue encapsulation Cavallo et al 2015). Crosslinked ECM biomaterials have also been shown to elicit a proinflammatory macrophage phenotype, rather than the anti-inflammatory and pro-remodeling phenotype induced by the native ECM bioscaffold Keane et al 2012).…”

“…ECM degradation also appears necessary to drive the inflammatory response toward resolution, avoiding the presence of a chronic inflammatory scenario. ECM degradation products produced during tissue remodeling, called cryptic peptides (Anderson et al 2008;Agrawal et al 2011a,b;Daly et al 2012), together with the release of the GFs retained in the ECM (Hodde et al 2001;Rieder et al 2004;Badylak 2014;Cavallo et al 2015), are believed to be responsible for many aspects of ECM-mediated bioactivity. Cryptic peptides are either created or exposed after the proteolysis of ECM components such as collagen, laminin, and fibronectin and their bioactivity is not present in the parent molecule (Anderson et al 2008;Daly et al 2012).…”

Remodeling of Noncrosslinked Acellular Dermal Matrices in a Rabbit Model of Ventral Hernia Repair

“…Some authors have argued that modifying the extracellular structure of the collagenous matrix by crosslinking could prevent host cell penetration and neovascularization and thus impair the remodeling process [12]. Other authors [20] reported that HDMI collagen crosslinking of porcine dermis scaffolds reduced the early histological remodeling profile but did not significantly impact the tensile strength or stiffness of graft-tissue complexes in a porcine model of ventral hernia repair. Deeken et al [21] claim that this limitation of crosslinked meshes may be insignificant in the long term, reporting that although crosslinking differentiated biological meshes early on, at 1 year, histological features such as cell penetration and neovascularization were no longer affected.…”

Surgical mesh for ventral incisional hernia repairs:Understanding mesh design

“…For example, cross-linked porcine meshes are more antigenic and, are thus, replaced by scar, whereas non-cross-linked meshes are less antigenic and are replaced by regenerate tissue. Regenerate tissue exhibits a greater degree of cellular infiltration, degradation, deposition of extracellular matrix, neovascularization, lower inflammatory cell response, and less scar encapsulation, whereas scar tissue has limited host cell and vessel infiltration, more fibrotic matrix, and aligned collagen deposition (40,95).…”