Promotion of Acellular Dermal Matrix Resolution In Vitro by Matrix Metalloproteinase-2

Abstract

Objective:To determine whether acellular human dermis is degraded by matrix metalloproteinases (MMPs), a large class of matrix-degrading enzymes. Methods:The degradation of acellular human dermis specimens was evaluated in vitro. Wild-type murine fibroblasts with a broad-spectrum MMP inhibitor, GM6001, and MMP-2-deficient fibroblasts were placed on the basement membrane and dermal surfaces of acellular human dermis. Matrix degradation and fibroblast infiltration into the matrix were assessed after a 20-day incubation period. Results:The basement membrane thickness of the specimens cultured with wild-type fibroblasts was significantly less than that of specimens cultured with GM6001 (PϽ.001), and the infiltration of fibroblasts into the der-mal surface was limited by the addition of GM6001 (P=.002). To determine whether MMP-2 was involved in this in vitro phenotype, MMP-2-deficient fibroblasts were assessed in comparison with wild-type fibroblasts. Wildtype fibroblasts degraded the basement membrane surface (PϽ.001) and infiltrated the dermal surface (P=.003) more efficiently than did MMP-2-deficient fibroblasts. Conclusions:The results from our in vitro experiments suggest that MMPs and specifically MMP-2 may play an important role in the resorption of acellular human dermis. Addition of MMP inhibitors to implanted dermal matrices may slow fibroblast infiltration and improve their longevity in vivo.

Addition of platelet‐rich plasma supports immune modulation and improved mechanical integrity in Alloderm mesh for ventral hernia repair in a rat model

“…Previous studies also suggest that a pharmacologically induced immunosuppressed state is associated with fewer complications and hernia recurrence when Alloderm is used for repair (Brewer et al, 2011; Misra et al, 2008). As Alloderm is largely a matrix of collagen and elastin, the presence of chronic inflammatory cells can be detrimental to its longevity due to factors involved in remodeling, such as MMPs that are part of the inflammatory enzymatic milieu (Carlson, Lee, & Pierce, 2013; Han et al, 2009; Lindman et al, 2006; Nagase, Visse, & Murphy, 2006; Singh et al, 2014). The ability of PRP to quell the inflammatory degradation of the graft is evidenced by the preservation of ADM thickness in the experimental arm compared with the control arm (Figure 3), and indeed our data suggest this may be a result of reduced MMP expression and increased Timp1 in PRP‐treated mesh (Figure 6).…”

Adipose-Derived Neural Stem Cells Combined with Acellular Dermal Matrix as a Neural Conduit Enhances Peripheral Nerve Repair

“…Currently, acellular dermal matrix (ADM) is used primarily for research into healing severe wounds such as burns and chronic wounds [16][17][18] , and its in vivo metabolism and microstructure are well established [19][20][21][22] . The ductility and plasticity of ADM suggest that it is potentially useful for repair of nerve gaps of various sizes in nerves of different diameters, and that it could be combined with neuro-engineered materials for future benefits to patient.…”

In VivoComparison of Three Human Acellular Dermal Matrices for Breast Reconstruction

“…Normally, throughout the process of wound healing, the levels of MMPs increase in an acute wound and decrease as wound healing occurs. MMP-2 (gelatinase A, 72-kDa gelatinase) can degrade several matrix components including collagen types I, IV, V, VII, XI, and laminin (36). MMP-3 has the ability to hydrolyse collagen types II, III, IV, IX and laminin, while MMP9 (gelatinase B, 72 kDa) is able to degrade collagen types III, IV, V, XIV and elastin (37,38).…”