Fibrin glue mesh fixation combined with mesenchymal stem cells or exosomes modulates the inflammatory reaction in a murine model of incisional hernia.

Surgical meshes are effective and frequently used to reinforce soft tissues. Fibrin glue (FG) has been widely used for mesh fixation and is also considered an optimal vehicle for stem cell delivery. The aim of this preclinical study was to evaluate the therapeutic effect of MSCs and their exosomes combined with FG for the treatment of incisional hernia. A murine incisional hernia model was used to implant surgical meshes and different treatments with FG, MSCs and exo-MSCs were applied. The implanted meshes were evaluated at day 7 by anatomopathology, cellular analysis of infiltrating leukocytes and gene expression analysis of TH1/TH2 cytokines, MMPs, TIMPs and collagens. Our results demonstrated a significant increase of anti-inflammatory M2 macrophages and TH2 cytokines when MSCs or exo-MSCs were used. Moreover, the analysis of MMPs, TIMPs and collagen exerted significant differences in the extracellular matrix and in the remodeling process. Our in vivo study suggests that the fixation of surgical meshes with FG and MSCs or exo-MSCs will have a beneficial effect for the treatment of incisional hernia in terms of improved outcomes of damaged tissue, and especially, in the modulation of inflammatory responses towards a less aggressive and pro-regenerative profile. STATEMENT OF SIGNIFICANCE: The implantation of surgical meshes is the standard procedure to reinforce tissue defects such as hernias. However, an exacerbated and persistent inflammatory response secondary to this implantation is frequently observed, leading to a strong discomfort and chronic pain in the patients. In many cases, an additional surgical intervention is needed to remove the mesh. This study shows that mesenchymal stem cells and their exosomes, combined with a fibrin sealant, can be used for the successful fixation of these meshes. This new therapeutic approach, assayed in a murine model of incisional hernia, favors the modulation of the inflammatory response towards a less aggressive and pro-regenerative profile.

[Actual aspects of treatment of postoperative abdominal hernia in patients with obesity].

The experience of conduction of simultant operations in 103 patients, treated for postoperative abdominal hernia and obesity, was summarized. The necessity of the simultant operation conduction in such patients is based on the determined fact of impact of associated diseases on pathogenetic mechanisms of the hernia development and possibility of postoperative complications occurrence. The simultant operations application in patients, suffering postoperative abdominal hernia, are not associated with increase of postoperative complications occurrence or duration of treatment, they constitute a progressive trend in surgery, securing also the hernia recurrence prophylaxis.

[Immunomorphological reaction of organism in prosthetic plasty of the anterior abdominal wall using polypropylene mesh in patients, suffering postoperative abdominal hernia].

Clinico-experimental studying the immunomorphological reactions variants in the prosthesis of anterior abdominal wall using synthetic polypropylene mesh was conducted. In 70 patients, operated on for postoperative hernia of abdominal wall using "on lay" method and the immune state were studied up by means of investigation of proinflammatory and anti-inflammatory cytokines content, in part, of tumor necrosis factor-alpha; (TNF-alpha), IL-8, IL-4. Morphological investigations were conducted in experiment on 100 the Vistar line mices, there were studied reactions of fibroblasts, macrophages, lymphocytes and leucocytes. The results of the immunological and morphological reactions on polypropylene obtained trust the necessity of differentiated approach application for the choice of the synthetic prosthesis kind, taking into account its biocompatibility, physical properties, the hernial defect size etc.

Immune response to xenogeneic matrix grafts used in pediatric surgery.

BACKGROUND: Lyoplant is an acellular, bovine derived extracellular matrix (ECM) that has been used for tissue remodelling and repair in numerous xenotransplantations. The aim of our study was to evaluate the inflammatory response and tensile strength after xenogeneic matrix (Lyoplant) implantation compared to the more widely used synthetic polypropylene matrix. METHODS: Full-thickness abdominal wall defects were created in 15 Wistar WU rats and reconstructed with either a Lyoplant matrix (B. Braun Aesculap, Tuttlingen, Germany) or a Prolene matrix (a polypropylene matrix [PPP]; Prolene, Ethicon, Norderstedt, Germany). Animals in both the treatment and the control groups were checked daily for local and systemic complications. Bodyweight was recorded and the possible development of a hernia was monitored. After 6 weeks the abdomen was reopened and adhesions to the intestine were determined. Histopathology and immunohistochemistry were performed to evaluate the immunological reaction to the xenograft. RESULTS: Compared to the untreated animals, all rats had a physiological growth and bodyweight curve: No wound infection was observed during the experiment. An abdominal hernia developed at the implant site only in one rat treated with a PPP matrix. All other animals had an excellent clinical recovery and good cosmetic results. PPP animals showed a pronounced inflammatory response indicated by an increased number of fibroblasts. The Lyoplant matrix implantation induced an infiltration of CD4 and CD68 positive cells. In addition, active neovascularization was found, indicating a remodelling process. The inflammatory response in Lyoplant treated animals was significantly milder than in PPP implanted rats. Interestingly, some CD8 positive cells were detected in the Lyoplant group. CONCLUSION: A xenogeneic extracellular matrix, such as Lyoplant, may induce an immune response which is predominantly TH2-like and comparable with a remodelling reaction rather than rejection.

Production of cytokines at the operation site.

BACKGROUND AND AIM: Cytokines are part of a family of molecules involved in the initiation, control and termination of the events that occurs in wound healing process. Aim of this study was to evaluate the production of some cytokines [interleukin (IL)-6, IL-10, IL-1alpha, IL-1ra, interferon (IFN)-gamma] in the drainage wound fluid from patients undergoing incisional hernia repair. METHODS: Ten female patients with abdominal midline incisional hernia undergoing to surgical repair were included in this study. In all cases a closed suction drain was placed in the wound below the fascia and it was removed on the 4th postoperative day. Wound fluid was collected on the 1st, 2nd, 3rd and 4th day and its amount in each time was recorded. The production of IL-6, IL-10, IL-1alpha, IL-1ra and IFN-gamma were evaluated as quantity produced in 24 hour. RESULTS: In all patients the amount of drain fluid from surgical wound was highest on the 1st day after surgery, afterwards there is a significant reduction. The production of all cytokines evaluated was highest on the 1st day decreasing on the 2nd day except for IL-1alpha that not show any modification. The produciton of IL-1ra, IL-6, IL-1alpha and IL-10 was significantly reduced on the 3rd and 4th postoperative day in comparison with the respectively values recorded on the 1st day, whereas IFN-gamma levels were similar. CONCLUSIONS: The dosage of cytokines in the drain fluid led us to better evaluated the events that follow surgical wound and their analysis offers further information in the role of cytokines in healing process, with the goal to get supportive treatments to promote the best evolution.