Comparison of the host macrophage response to synthetic and biologic surgical meshes used for ventral hernia repair

Abstract

The host innate immune response to a surgical mesh is arguably the most important determinant of tissue remodeling and functional outcome. Macrophage phenotype and the associated secretion of pro-inflammatory or anti-inflammatory cytokines during the first 10–14 days following implantation has been strongly associated with downstream events such as chronic inflammation vs. functional tissue remodeling, respectively, and the associated clinical consequences. A persistent, pro-inflammatory (M1-like) macrophage phenotype is typically associated with fibrosis and scarring. In contrast, an early transition to a regulatory, pro-remodeling (M2-like) macrophage phenotype is predictive of organized, site-appropriate connective tissue deposition. The ratio of M2-like to M1-like macrophages in the early post-implantation period defines the microenvironmental milieu and the associated tissue response. The present study evaluated the early macrophage response to a synthetic non-resorbable (Bard^® Mesh), synthetic resorbable (TIGR^® Matrix Surgical Mesh and GORE^® BIO-A^® Tissue Reinforcement), synthetic mesh composed of the naturally occurring molecule 4-hydroxybutyrate, (Phasix™ Mesh), and a biologic surgical mesh composed of dermal extracellular matrix (Strattice™ Reconstructive Tissue Matrix); all of which are used in ventral hernia repair. The spatiotemporal distribution of pro-inflammatory (CD68⁺CD86⁺TNF-α⁺) and pro-remodeling (CD68⁺CD206⁺) macrophages, and the remodeling response in terms of vascularization, total number of infiltrating cells, presence of multinucleate giant cells (MNGC), and cell layer thickness around the implanted materials was evaluated at 3, 7, 14, 21, and 35 days post implantation. Results showed an association of the synthetic non-resorbable and resorbable meshes with a robust, pro-inflammatory response within 3 days of implantation, and an increased presence of MNGC around the mesh fibers at longer time points. Phasix™ Mesh was associated with an increased presence of M2-like macrophages immediately adjacent to the mesh fibers at earlier time points, and a favorable tissue remodeling outcome at 35 days. Results of the present study are consistent with the premise that an early shift of M1-like to M2-like macrophages is associated with favorable outcomes, including reduced fibrosis, at later time points.