Gemma Pascual

Fibroblasts from the transversalis fascia of young patients with direct inguinal hernias show constitutive MMP-2 overexpression.

ObjectiveTo determine the expression pattern of certain metalloproteinases (MMPs) known to be involved in the degradation of the extracellular matrix in cultured fibroblasts from the transversalis fascia (TF) of patients with inguinal hernia. Summary Background DataInguinal hernia is a common pathology, the cause of which remains unknown. It is, however, clear that the TF is one of the anatomical structures that may impede the formation of hernias, and particularly the direct type of hernia. In previous studies the authors found enhanced MMP-2 expression in TF specimens in vivo. The persistence of increased expression in cultured fibroblasts might support the idea of a genetic defect as the cause for this pathology. MethodsFibroblasts from the TF of patients with direct and indirect inguinal hernia were cultured and compared with those obtained from control TF in terms of MMP (MMP-2 and MMP-9) expression. ResultsSignificant active MMP-2 expression was shown by TF fibroblasts from young patients with direct hernias. These findings were confirmed by immunosorbent assay, immunoblotting, and zymography of the fibroblast culture media. No MMP-9 expression was detected. ConclusionThese results indicate that MMP-2 may be involved in the TF matrix degradative process in patients with direct hernia. The persistence of changes in MMP-2 levels in the cell cultures appears to suggest a genetic defect or irreversible change as the origin of this pathology rather than environmental factors, which may later participate in the development of the hernial process.

Mechanical behaviour of synthetic surgical meshes: Finite element simulation of the herniated abdominal wall

The material properties of meshes used in hernia surgery contribute to the overall mechanical behaviour of the repaired abdominal wall. The mechanical response of a surgical mesh has to be defined since the haphazard orientation of an anisotropic mesh can lead to inconsistent surgical outcomes. This study was designed to characterize the mechanical behaviour of three surgical meshes (Surgipro®, Optilene® and Infinit®) and to describe a mechanical constitutive law that accurately reproduces the experimental results. Finally, through finite element simulation, the behaviour of the abdominal wall was modelled before and after surgical mesh implant. Uniaxial loading of mesh samples in two perpendicular directions revealed the isotropic response of Surgipro® and the anisotropic behaviour of Optilene® and Infinit®. A phenomenological constitutive law was used to reproduce the measured experimental curves. To analyze the mechanical effect of the meshes once implanted in the abdomen, finite element simulation of the healthy and partially herniated repaired rabbit abdominal wall served to reproduce wall behaviour before and after mesh implant. In all cases, maximal displacements were lower and maximal principal stresses higher in the implanted abdomen than the intact wall model. Despite the fact that no mesh showed a behaviour that perfectly matched that of abdominal muscle, the Infinit® mesh was able to best comply with the biomechanics of the abdominal wall.

Early tissue incorporation and collagen deposition in lightweight polypropylene meshes: bioassay in an experimental model of ventral hernia.

BACKGROUND This study was designed to assess the early host tissue incorporation of several polypropylene lightweight (PP-LW) meshes used to repair abdominal wall defects and to correlate collagen deposition with the biomechanical response shown by PP-LW versus polypropylene heavyweight (PP-HW) meshes. METHODS Ventral hernial defects (7 x 5 cm) were created in the anterior abdominal wall of New Zealand rabbits and repaired by fixing PP-LW mesh of different pore sizes or a low porosity HW mesh to the edges of the defect. Rabbits were killed 14 days after implant, and specimens were taken from the central mesh area to examine collagen deposition by light microscopy, real time reverse transcription polymerase chain reaction, immunohistochemistry, and Western blotting. The biomechanical resistance of the biomaterials was also assessed. RESULTS All the materials showed excellent incorporation in host tissue. Relative amounts of collagen III mRNA were considerably higher than collagen I mRNA. Higher collagen I and III mRNA levels were noted for pore sizes equal to or greater than 3.45 +/- 0.19 mm(2) (Ultrapro/Optilene Elastic. These two meshes showed significantly higher levels of collagen III than Parietene and Surgipro with smaller pores. Biomechanical resistance values for Optilene were significantly higher than those recorded for Surgipro and Parietene. CONCLUSIONS (a) LW meshes of pore size larger than 3 mm(2) induced the genetic overexpression of collagen types I and III; (b) the larger pore-sized LW meshes induced more collagen type III deposition and its faster conversion to collagen I; (c) Optilene, the most porous LW mesh examined, showed the greatest tensile strength 14 days after implant.

Neoperitoneal formation after implantation of various biomaterials for the repair of abdominal wall defects in rabbits

OBJECTIVE To study the interfaces between the visceral peritoneum and some of the biomaterials used to repair defects in the abdominal wall. DESIGN Animal study. SETTING School of medicine, Spain. MATERIAL 48 New Zealand white rabbits divided into 4 groups of 12 each. INTERVENTIONS Full thickness defects 50 x 70 mm were created in the abdominal wall and repaired with polytetrafluoroethylene (PTFE, Soft Tissue Patch), one of two polypropylene patches (Marlex and Prolene), or lyophylised dura mater (Lyo-Dura). 3 animals from each group were killed at 14, 30, 60 and 90 days and specimens examined by light microscopy, scanning electron microscopy, and immuno histochemistry by labelling of macrophages with RAM-11, a specific monoclonal antibody (MoAb). MAIN OUTCOME MEASURES Infection, healing, development of adhesions, and histological appearance of the interface. RESULTS Tissues responded similarly to materials of similar structures. Layered prostheses (PTFE and Lyo-Dura) caused formation of a well organised neoperitoneum with few adhesions to the abdominal viscera (loose adhesions in 2 animals in each group), whereas the mesh prostheses generated a disorganised neoperitoneum with many adhesions (Marlex loose adhesions 3, firm 8, and integrated 1; Prolene loose adhesions 2, firm 8, and integrated 2). Lyo-Dura was associated with the formation of areas of calcification. Labelling of macrophages with the MoAb showed that they were in direct contact with all materials studied. CONCLUSIONS Layered biomaterials with little or no porosity (PTFE and Lyo-Dura) are the most suitable of the four for implantation in sites where the prosthesis is in contact with the visceral peritoneum, because they induce minimal adhesions.

Comparing the Behavior of Different Polypropylene Meshes (Heavy and Lightweight) in an Experimental Model of Ventral Hernia Repair

New generation prosthetic biomaterials for abdominal wall repair have been designed to be less dense, by having larger pores than that of the standard polypropylene meshes, to improve abdominal wall compliance. The aim of the present study was to analyze the functional and morphologic properties of these new meshes. For this purpose, 7 x 5 cm(2) defects were created in the anterior abdominal wall of 36 male New Zealand White rabbits and repaired using different polypropylene meshes: a heavyweight mesh (HW), Surgipro, and two lightweight meshes (LW), Parietene and Optilene. Six animals each implanted with biomaterial were sacrificed on postoperative days 14 and 90. Histological and morphometric analysis, adhesion assessment, and biomechanical resistance tests were performed. Similar behavior was shown by the LW and HW meshes in terms of the adhesions and macrophage response induced. After 14 days, the tensile strength of Optilene was greater than the strengths recorded for the other two biomaterials, probably because of its high elasticity. By 90 days, however, the tensile strengths of the three biomaterials were comparable. In conclusion, despite an initial tensile strength advantage shown by the mesh with larger pores, at 90 days postimplant, tensile strengths were similar. Compared with HW, LW prostheses have the benefit that less foreign material was implanted, preserving the elasticity of the recipient host tissue.

Postimplant behavior of lightweight polypropylene meshes in an experimental model of abdominal hernia.

Background. Over the years, reticular prostheses have undergone changes in their structure and composition to give rise to todays partially absorbable lightweight meshes. This study was designed to assess the biological and biomechanical behavior of these prostheses to establish whether they offer any advantages over nonabsorbable lightweight polypropylene prostheses. Materials and Methods. 7 × 5 cm defects were created in the anterior abdominal wall of New Zealand White rabbits and repaired by securing different prostheses to the edges of the defect with a running 4/0 polypropylene suture. The lightweight biomaterials compared were two nonabsorbable meshes: Parietene® and Optilene elastic®, and two partially absorbable prostheses: Vypro II® and Ultrapro®. At 14 and 90 days postimplant, tissue/prosthesis specimens were subjected to histological, immunohistochemical, shrinkage, and biomechanical analyses. Results. Adhesion formation on the peritoneum-facing surface of the meshes was significantly less extensive in the meshes with absorbable components at 90 days postimplant. The newly formed tissue around the prosthetic filaments was comprised of collagen fibers, fibroblasts, blood vessels, and macrophages. The partially absorbable meshes showed higher macrophage proportions (due to remnants of absorbable material and their structure) than the nonabsorbable meshes at 90 days, although differences were not significant. At 90 days postimplant, similar tensile strengths were recorded for all the implants. Conclusions. All the prosthetic materials induced good host tissue ingrowth, with no significant differences in tensile strength observed. Our findings suggest that partially absorbable lightweight prostheses could offer advantages over nonabsorbable lightweight meshes since less foreign material persists in the recipient, improving abdominal wall compliance.

Long-term anisotropic mechanical response of surgical meshes used to repair abdominal wall defects

Routine hernia repair surgery involves the implant of synthetic mesh. However, this type of procedure may give rise to pain and bowel incarceration and strangulation, causing considerable patient disability. The purpose of this study was to compare the long-term behaviour of three commercial meshes used to repair the partially herniated abdomen in New Zealand White rabbits: the heavyweight (HW) mesh, Surgipro(®) and lightweight (LW) mesh, Optilene(®), both made of polypropylene (PP), and a mediumweight (MW) mesh, Infinit(®), made of polytetrafluoroethylene (PTFE). The implanted meshes were mechanical and histological assessed at 14, 90 and 180 days post-implant. This behaviour was compared to the anisotropic mechanical behaviour of the unrepaired abdominal wall in control non-operated rabbits. Both uniaxial mechanical tests conducted in craneo-caudal and perpendicular directions and histological findings revealed substantial collagen growth over the repaired hernial defects causing stiffness in the repair zone, and thus a change in the original properties of the meshes. The mechanical behaviour of the healthy tissue in the craneo-caudal direction was not reproduced by any of the implanted meshes after 14 days or 90 days of implant, whereas in the perpendicular direction, SUR and OPT achieved similar behaviour. From a mechanical standpoint, the anisotropic PP-lightweight meshes may be considered a good choice in the long run, which correlates with the structure of the regenerated tissue.

Evaluation of the acute scarring response to the implant of different types of biomaterial in the abdominal wall

Since the short-term, acute scarring process induced by a biomaterial may condition the evolution of the repair process, the present investigation evaluates the behavior of polytetrafluoroethylene (PTFE) and polypropylene (PL) biomaterials in the initial stages of repair. Three PTFE biomaterials (Mycro Mesh®, Dual Mesh® and Soft Tissue Patch®) and one PL biomaterial (Marlex®) were employed to repair defects created in the abdominal wall of New Zealand rabbits. Animals were sacrificed at 3 or 7 days. Specimens were obtained for light and scanning electron microscopy, and immunohistochemical analysis using the RAM-11 monoclonal antibody for rabbit macrophages. The PL implants showed substantial adhesion formation with viscera. Lower adhesion formation was detected in the PTFE implants. The evolution of the acute phase of the repair process was similar for each PTFE biomaterial. At 3 days post implant, an incipient neoperitoneum was detected which was fully established after 7 days. The behavior of the PL implant was similar, although a greater amount of reticular granulation was detected. The neoformed peritoneum was irregular. Few RAM-11-labeled macrophages were detected in all cases. The acute phase of the tissue repair process induced by the implant of PTFE and PL biomaterials generally proceeds along similar lines to a normal repair process. However, the use of microporous, laminar materials seems to favor the early establishment of a well-defined neoperitoneal layer.

TGF-β1 Upregulation in the Aging Varicose Vein

Background: Although the etiology of venous insufficiency is not well understood, immune response and aging are beginning to emerge as contributing factors. Factors involved in tissue remodeling such as TGF-β1 also seem to play an important role in extracellular matrix production. The aim of this study was to explore the relationship between chronic venous insufficiency and TGF-β1 examining the latent/mature form of TGF-β1 and the presence of mast cells. Effects of age were also evaluated. Methods: Saphenous veins were obtained from patients subjected to aortocoronary bypass (controls) and undergoing varicose vein surgery. These were immunolabeled using anti-LAP TGF-β1/anti-TGF-β1 antibodies and subjected to Western blot. Mast cell population was identified by metachromatic staining.Results:Latent TGF-β1 was significantly reduced in varicose veins from older subjects. In contrast, smooth muscle cells obtained from the varicosities showed intense levels. Mature TGF-β1 significantly differed between healthy and varicose veins. No mature TGF-β1 was detected in the cell cultures. Mast cell number and degranulation were increased with aging and varicose disease, colocalizing with the mature form of TGF-β1. Conclusion: Aging and varicose pathology induce dysregulation of TGF-β1 that could play an important role in the fibrous process, representing the final stages of venous insufficiency.

Understanding the Passive Mechanical Behavior of the Human Abdominal Wall

The aim of this work is to present a methodology to model the passive mechanical behavior of the human abdomen during physiological movements. From a mechanical point of view, it is possible to predict where hernia formation is likely to occur since the areas that support higher stresses can be identified as the most vulnerable ones. For this purpose, a realistic geometry of the human abdomen is obtained from magnetic resonance imaging. The model defines different anatomical structures of the abdomen, including muscles and aponeuroses, and anisotropic mechanical properties are assigned. The finite element model obtained from the geometric human model, which includes initial strains, is used to simulate the anisotropic passive behavior of the healthy human abdomen under intra-abdominal pressure. This study demonstrates that the stiffest structures, namely aponeuroses and particularly the linea alba, are the structures that perform the most work in the abdomen. Thus, the linea alba is the most important unit contributing to the mechanical stability of the abdominal wall.