Evaluation of a Novel Hybrid Viable Bioprosthetic Mesh in a Model of Mesh Infection.

BACKGROUND: The reported incidence of mesh infection in contaminated operative fields is as high as 30% regardless of material used. Our laboratory previously showed that augmenting acellular bioprosthetic mesh with allogeneic mesenchymal stem cells (MSC) enhances resistance to bacterial colonization in vivo and preserves mesh integrity. This study's aim was to determine whether augmentation of non-crosslinked porcine dermis (Strattice) with commercially available, cryopreserved, viable MSC-containing human placental tissue (Stravix) similarly improves infection resistance after inoculation with Escherichia coli (E. coli) using an established mesh infection model. METHODS: Stravix was thawed per manufacturer's instructions and 2 samples were tested for cell viability using a Live/Dead Cell assay at the time of surgery. Rats (N = 20) were implanted subcutaneously with 1 piece of Strattice and 1 piece of hybrid mesh (Strattice + Stravix sutured at the corners). Rats were inoculated with either sterile saline or 106 colony-forming units of E. coli before wound closure (n = 10 per group). At 4 weeks, explants underwent microbiologic and histologic analyses. RESULTS: In E. coli-inoculated animals, severe or complete mesh degradation concurrent with abscess formation was observed in 100% (10/10) hybrid meshes and 90% (9/10) Strattice meshes. Histologic evaluation determined that meshes inoculated with E. coli exhibited severe acute inflammation, which correlated with bacterial recovery (P < 0.001). Viability assays performed at the time of surgery failed to verify the presence of numerous live cells in Stravix. CONCLUSIONS: Stravix cryopreserved MSC-containing human umbilical tissue does not improve infection resistance of a bioprosthetic mesh in vivo in rats after inoculation with E. coli.

Bone Marrow-Derived Mesenchymal Stem Cells Enhance Bacterial Clearance and Preserve Bioprosthetic Integrity in a Model of Mesh Infection.

BACKGROUND: The reported incidence of mesh infection in contaminated operative fields is as high as 30% regardless of the material used. Recently, mesenchymal stem cells (MSCs) have been shown to possess favorable immunomodulatory properties and improve tissue incorporation when seeded onto bioprosthetics. The aim of this study was to evaluate whether seeding noncrosslinked bovine pericardium (Veritas Collagen Matrix) with allogeneic bone marrow-derived MSCs improves infection resistance in vivo after inoculation with Escherichia coli (E. coli). METHODS: Rat bone marrow-derived MSCs at passage 3 were seeded onto bovine pericardium and cultured for 7 days before implantation. Additional rats (n = 24) were implanted subcutaneously with MSC-seeded or unseeded mesh and inoculated with 7 × 10(5) colony-forming units of E. coli or saline before wound closure (group 1, unseeded mesh/saline; group 2, unseeded mesh/E. coli; group 3, MSC-seeded mesh/E. coli; 8 rats per group). Meshes were explanted at 4 weeks and underwent microbiologic and histologic analyses. RESULTS: MSC-seeded meshes inoculated with E. coli demonstrated superior bacterial clearance and preservation of mesh integrity compared with E. coli-inoculated unseeded meshes (87.5% versus 0% clearance; p = 0.001). Complete mesh degradation concurrent with abscess formation was observed in 100% of rats in the unseeded/E. coli group, which is in contrast to 12.5% of rats in the MSC-seeded/E. coli group. Histologic evaluation determined that remodeling characteristics of E. coli-inoculated MSC-seeded meshes were similar to those of uninfected meshes 4 weeks after implantation. CONCLUSIONS: Augmenting a bioprosthetic material with stem cells seems to markedly enhance resistance to bacterial infection in vivo and preserve mesh integrity.

Long-term epigenetic alterations in a rat model of Gulf War Illness.

Gulf War Illness (GWI) is a chronic, multisymptom illness that affects 25% of the 700,000 US veterans deployed to the Persian Gulf during the 1990-1991 Gulf War. Central nervous system impairments are among the most common symptoms reported, including memory dysfunction and depression. After 25 years, the diagnosis remains elusive, useful treatments are lacking, and the cause is poorly understood, although exposures to pyridostigmine bromide (PB) and pesticides are consistently identified to be among the strongest risk factors. Epigenetic changes including altered microRNA (miRNA) expression and DNA methylation play an important role in learning, memory, and emotion regulation and have been implicated in various neurological disorders. In this study, we used an established rat model of GWI to determine whether 1) chronic alterations in miRNA expression and global DNA methylation and DNA hydroxymethylation are mechanisms involved in the pathobiology of GWI, and 2) plasma exosome small RNAs may serve as potential noninvasive biomarkers of this debilitating disease. One year after a 28-day exposure regimen of PB, DEET (N,N-diethyl-3-methylbenzamide), permethrin, and mild stress, expression of 84 mature miRNAs and global 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) content were analyzed in the brains of GWI rats and vehicle controls by PCR array and enzyme-linked immunosorbent assay, respectively. Plasma exosome RNA next-generation sequencing analysis was performed in pooled samples to discover potential noninvasive biomarkers. We found that combined exposure to low doses of GW-related chemicals and mild stress caused epigenetic modifications in the brain that persisted one year after exposure, including increased expression of miR-124-3p and miR-29b-3p in the hippocampus and regional alterations in global 5mC and 5hmC content. GW-relevant exposures also induced the differential expression of two piwi-interacting RNAs (piRNAs) in circulation (piR-007899 and piR-019162). Results from this study implicate a role for epigenetic alterations in GWI. Evaluation of the diagnostic potential of plasma exosome RNAs in veterans with GWI is warranted.

An experimental comparison of the effects of bacterial colonization on biologic and synthetic meshes.

PURPOSE: Biologic meshes are being used with increasing frequency to repair contaminated abdominal wall defects despite high long-term recurrence and infection rates associated with their use. Recent clinical reports describing the success of lightweight, macroporous synthetic meshes in contaminated ventral hernia repairs have led some surgeons to challenge the belief that synthetics are contraindicated in contaminated fields. We aimed to determine whether a frequently used biologic mesh (Strattice(TM)) is more resistant to bacterial colonization than macroporous synthetic mesh (Parietex(TM) Progrip(TM)) after inoculation with two common pathogens. METHODS: Rats (n = 48) were implanted subcutaneously with Strattice(TM) or Progrip(TM). Meshes were inoculated with sterile saline or a suspension containing 10(6) colony-forming units of Staphylococcus aureus or Escherichia coli prior to wound closure (n = 8 per subgroup). Meshes were explanted at 4 weeks and underwent microbiologic and histologic analyses. RESULTS: Progrip(TM) demonstrated superior bacterial clearance compared to Strattice(TM) (E. coli, 88 vs. 17% clearance, p = 0.03; S. aureus, 75 vs. 50%, p = 0.61; combined bacterial strains, 81 vs. 36%, p = 0.02; respectively). In the Strattice(TM) group, severely degraded meshes were observed in 100% of animals inoculated with E. coli (but 0% inoculated with S. aureus). In contrast, all Progrip(TM) meshes remained intact regardless of inoculum. Scores for neovascularization were higher in the synthetic group irrespective of contamination (p < 0.05). CONCLUSIONS: Biologic meshes may not be more resistant to bacterial colonization than reduced-weight synthetics, and their resistance may differ in response to different pathogens. The routine use of biologics in contaminated ventral hernia repair should be questioned, particularly in the presence of E. coli.