Modification of collagen formation by mesenchymal stem cells isolated from human adipose tissue in culture and after autotransplantation for abdominal hernia plasty.

Mesenchymal stem cells from the adipose tissue of patients with postoperative hernias produce excessive amounts of collagen III, which shifts the balance between type III and type I collagens. The proposed technique of pretransplantation preparation allows in vitro stimulation collagen formation processes with predominant activation of collagen I synthesis and normalization of proportion between different collagen types. Abdominal wall repair with polypropylene surgical mesh in combination with autotransplantation of mesenchymal stem cells reduced the collagen III to collagen I ratio due to activation of collagen I synthesis and suppression of collagen III production, which had a positive effect on the structure of in vivo formed connective tissue.

Abdominal aortic aneurysm and abdominal wall hernia as manifestations of a connective tissue disorder.

BACKGROUND: Abdominal aortic aneurysms (AAAs) and abdominal wall hernias represent chronic degenerative conditions. Both aortic aneurysms and inguinal hernias share common epidemiologic features, and several investigators have found an increased propensity for hernia development in patients treated for aortic aneurysms. Chronic inflammation and dysregulation in connective tissue metabolism constitute underlying biological processes, whereas genetic influences appear to be independently associated with both disease states. A literature review was conducted to identify all published evidence correlating aneurysms and hernias to a common pathology. METHODS: PubMed/Medline was searched for studies investigating the clinical, biochemical, and genetic associations of AAAs and abdominal wall hernias. The literature was searched using the MeSH terms "aortic aneurysm, abdominal," "hernia, inguinal," "hernia, ventral," "collagen," "connective tissue," "matrix metalloproteinases," and "genetics" in all possible combinations. An evaluation, analysis, and critical overview of current clinical data and pathogenic mechanisms suggesting an association between aneurysms and hernias were undertaken. RESULTS: Ample evidence lending support to the clinical correlation between AAAs and abdominal wall hernias exists. Pooled analysis demonstrated that patients undergoing aortic aneurysm repair through a midline abdominal incision have a 2.9-fold increased risk of developing a postoperative incisional hernia compared with patients treated for aortoiliac occlusive disease (odds ratio, 2.86; 95% confidence interval, 1.97-4.16; P < .00001), whereas the risk of inguinal hernia was 2.3 (odds ratio, 2.30; 95% confidence interval, 1.52-3.48; P < .0001). Emerging evidence has identified inguinal hernia as an independent risk factor for aneurysm development. Although mechanisms of extracellular matrix remodeling and the imbalance between connective tissue degrading enzymes and their inhibitors instigating inflammatory responses have separately been described for both disease states, comparative studies investigating these biological processes in aneurysm and hernia populations are scarce. A genetic predisposition has been documented in familial and observational segregation studies; however, the pertinent literature lacks sufficient supporting evidence for a common genetic basis for aneurysm and hernia. CONCLUSIONS: Insufficient data are currently available to support a systemic connective tissue defect affecting the structural integrity of the aortic and abdominal wall. Future investigations may elucidate obscure aspects of aneurysm and hernia pathophysiology and create novel targets for pharmaceutical and gene strategies for disease prevention and treatment.

Connective tissue alteration in abdominal wall hernia.

BACKGROUND: The aetiology and pathogenesis of abdominal wall hernia formation is complex. Optimal treatment of hernias depends on a full understanding of the pathophysiological mechanisms involved in their formation. The aim of this study was to review the literature on specific collagen alterations in abdominal wall hernia formation. METHODS: A computer-assisted search of the medical databases PubMed and Embase was performed, together with a cross-reference search of eligible papers. RESULTS: Fifty-two papers were included. Collagen alteration depended on the type of hernia; there were more pronounced changes in patients with a direct inguinal hernia than in those with an indirect inguinal hernia, recurrent inguinal hernia or incisional hernia. A consistent finding was a significant increase in immature type III collagen relative to the stronger type I collagen in patients with a hernia. This resulted in thinner collagen fibres with a correspondingly diminished biomechanical strength. It has been suggested that these alterations are due to variation in the synthesis, maturation or degradation of collagen by matrix metalloproteinases, in combination or alone. CONCLUSION: Hernia formation and recurrence is associated with altered collagen metabolism manifested by a decreased type I:III collagen ratio.

Evaluation of synthetic reticular hybrid meshes designed for intraperitoneal abdominal wall repair: Preclinical and in vitro behavior.

INTRODUCTION: Reticular hybrid meshes represent an alternative material for intraperitoneal repair of abdominal hernias. These consist of a reticular mesh coated or interwoven/knitted with inert materials. This study assesses the performance of two reticular polypropylene-containing hybrid meshes, TiMESH (coated with titanium) and DynaMesh (interwoven with polyvinylidene fluoride), in vitro, as well as their efficiency in adhesion prevention and tissue incorporation in an intraperitoneal model. METHODS: The mesothelialization capacity of TiMESH and DynaMesh was evaluated in vitro and compared to that of Surgipro (reticular bare polypropylene) and Preclude (laminar expanded polytetrafluoroethylene). Mesh fragments were placed on the intact parietal peritoneum of New Zealand white rabbits (n = 24), and laparoscopy performed 7 days post-surgery. Fourteen days post-implantation, adhesions were evaluated and host tissue incorporation, macrophage response, collagen expression (immunohistochemistry/RT-PCR) and neoperitoneum formation assessed. Adhesions and omental tissue were also examined. RESULTS: Mesh pores in reticular meshes were devoid of cells in the in vitro study. TiMESH, DynaMesh and Surgipro showed similar adhesion rates at 7/14 days and optimal tissue integration, with significant differences in comparison to Preclude. The greatest presence of macrophages was observed for TiMESH and was significant versus that for Preclude. Hybrid meshes revealed significantly higher collagen 1 mRNA expression in implants, with no differences in the levels of collagen 3. Omental samples from animals with a reticular mesh showed significantly greater collagen 1 mRNA levels. CONCLUSIONS: The reticular structure of a mesh limits the formation of a continuous mesothelial monolayer in vitro, regardless of its composition. The presence of titanium as a coating or polyvinylidene fluoride interwoven with polypropylene in a reticular structure did not prevent adhesions. The hybrid meshes showed proper integration and an increase in the mRNA Col 1 levels in the implant area compared to Surgipro or Preclude.

Association between abdominal hernia and the risk of subsequent dementia.

OBJECTIVE: Matrix metalloproteinases (MMPs) may play a role in the pathophysiology of neurodegenerative disease and hernia formation. This retrospective cohort study was designed to assess whether there is an association between hernia and the risk of dementia. MATERIALS AND METHODS: Patients (≥45 years) with hernias were identified between 2000 and 2008 from a longitudinal claims data of one million beneficiaries from Taiwan's National Health Insurance program. A control group of patients with comparable distributions of sex, age, socioeconomic status, urbanization, and medical comorbidities without hernia were chosen for matching in a ratio of 1:1. Patients previously diagnosed with dementia were excluded. Follow-up ended on December 31, 2013. Incidence rate of dementia was compared between patients with hernias and those without. Cox proportional hazards models were used to estimate hazards relative to those of the control group. RESULTS: After matching, there were 4,784 hernia and 4,784 nonhernia patients. Hernia patients showed a higher incidence rate and hazard ratio of dementia than those in nonhernia group (8.82 vs. 7.19/1,000 person-years; adjusted hazard ratio [aHR], 1.24; 95% CI, 1.07 to 1.45; p < .01). Advanced age (p < .0001), hypertension (p = .0139), head injury (p = .0003), and stroke (p = .041) were found to be risk factors for dementia, while patients with high socioeconomic status (p < .01) and history of coronary artery disease (p = .0292) were unlikely to develop dementia in our cohort study. CONCLUSION: Patients with hernias were associated with a higher incidence of dementia than those without. Our finding should be validated in further prospective studies with larger samples.

Fibrillin-1 in incisional hernias: an immunohistochemical study in scar and non-scar regions of human skin and muscle fasciae.

Incisional hernias represent one of the most common complications after laparotomy. Specific pre-operative risk factors have not yet been identified. Recent studies indicate that changes in extracellular matrix components such as collagen I and collagen III may be involved in hernia development. In the present study we have evaluated the significance of fibrillin-1 in hernia development as one of the main components of the extracellular matrix. Tissue samples from non-scar skin and muscle fascia of 12 patients with incisional hernias as well as from the respective scar tissues were obtained. Corresponding tissue samples of 10 patients with normal postoperative wound healing served as controls. Distribution of fibrillin-1 was evaluated immunohistochemically. Differences in fibrillin-1 distribution in the non-scar tissues of muscle fascia have been found in patients with incisional hernia, compared to those without hernia. In scar regions of both patient groups, slight differences in the pattern of fibrillin-1 were observed. A tendency to a differential deposition of fibrillin-1 in skin samples, although hardly quantifiable, was observed as well. Our results suggest that fibrillin-1 is a relevant factor contributing to tissue stability. Disturbances in its deposition, even before scar formation, may be an important factor to the development of incisional hernias.

The biology of hernia formation.

Abdominal wall hernias occur when tissue structure and function are lost at the load-bearing muscle, tendon, and fascial layer. The fundamental biologic mechanisms are primary fascial pathology or surgical wound failure. In both cases, cellular and extracellular molecular matrix defects occur. Primary abdominal wall hernias have been associated with extracellular matrix diseases. Incisional hernias and recurrent inguinal hernias more often involve a combination of technical and biologic limitations. Defects in wound healing and extracellular matrix synthesis contribute to the high incidence of incisional hernia formation following laparotomy.

Analysis of c-myc, PAI-1 and uPAR in patients with incisional hernias.

BACKGROUND: Disturbed wound healing leading to alterations in collagen composition has been thought to play a key role in the pathogenesis of incisional hernia formation. The aim of the present study was to further characterise the scarring process in such patients. METHODS: Mature skin scars from patients with either primary or recurrent incisional hernias were compared to mature abdominal skin scars from patients without hernias. The distribution of collagen types I and III was analysed using crosspolarisation microscopy. Expression of c-myc--a parameter for cell differentiation and proliferation--and of PAI-1 and uPAR--parameters of the proteolytic cascade in wound healing--were determined by immunohistochemistry. RESULTS: In agreement with previous studies, decreased collagen I/III ratios were found in patients with incisional hernias. In these patients, c-myc levels were significantly elevated whereas plasminogen activator inhibitor-1 (PAI-1) and urokinase-plasminogen activator receptor (uPAR) levels were only slightly increased. In contrast to controls, a significant correlation between c-myc, PAI-1 and uPAR expression and collagen I/III ratios was found in patients with incisional hernias. CONCLUSION: The differential correlation of collagen types and expression of c-myc, PAI-1 and uPAR within the scar tissue might represent a causal factor in incisional hernia formation.

Cross-Linked Cholecyst-Derived Extracellular Matrix for Abdominal Wall Repair.

Abdominal wall repair frequently utilizes either nondegradable or biodegradable meshes, which are found to stimulate undesirable biological tissue responses or which possess suboptimal degradation rate. In this study, a biologic mesh prototype made from carbodiimide cross-linked cholecyst-derived extracellular matrix (EDCxCEM) was compared with small intestinal submucosa (Surgisis®), cross-linked bovine pericardium (Peri-Guard®), and polypropylene (Prolene®) meshes in an in vivo rabbit model. The macroscopic appearance and stereological parameters of the meshes were evaluated. Tailoring the degradation of the EDCxCEM mesh prevents untimely degradation, while allowing cellular infiltration and mesh remodeling to take place in a slower but predictable manner. The results suggest that the cross-linked biodegradable cholecyst-derived biologic mesh results in no seroma formation, low adhesion, and moderate stretching of the mesh. In contrast to Surgisis, Peri-Guard, and Prolene meshes, the EDCxCEM mesh showed a statistically significant increase in the volume fraction (Vv) of collagen (from 34% to 52.1%) in the central fibrous tissue region at both day 28 and 56. The statistically high length density (Lv), of blood vessels for the EDCxCEM mesh at 28 days was reflected also by the higher cellular activity (high Vv of fibroblast and moderate Vv of nuclei) indicating remodeling of this region in the vicinity of a slowly degrading EDCxCEM mesh. The lack of mesh area stretching/shrinkage in the EDCxCEM mesh showed that the remodeled tissue was adequate to prevent hernia formation. The stereo-histological assays suggest that the EDCxCEM delayed degradation profile supports host wound healing processes including collagen formation, cellular infiltration, and angiogenesis. The use of cross-linked CEM for abdominal wall repair is promising.

Biological and proteomic characterization of a composite mesh for abdominal wall hernia treatment: Reference Study.

AIMS: The industrial development of a product requires performing a deep analysis to highlight its characteristics useful for future design. The clinical use of a product stimulates knowledge improvement about it in a constant effort of progress. This work shows the biological characterization of CMC composite mesh. CMC polypropylene prosthesis was seeded with Human fibroblast BJ. Samples (cells and medium) were collected at different time points in order to perform different analysis: inflammatory markers quantification; collagens immunohistochemistry; matrix metalloproteinases zimography; extracellular matrix proteomic profile. FINDINGS: CMC presented a good cell viability rate and cell growth during the 21 days. The inflammatory profile showed an initial secretion of anti-inflammatory IL-10 and a final increase of pro-inflammatory IL-6. Immunocytochemistry highlighted a similar Collagen type I/type III ratio. The proteomic analysis evidenced the ECM protein content profile composed, mainly, by collagens, fibronectin, laminin. MMPs resulted both expressed when in contact to mesh. CONCLUSIONS: CMC shows a good cell biocompatibility and growth. The increase of pro-inflammatory markers could stimulate proliferation, influencing the integration process in human body. Proteomics highlights the ECM modulation by CMC. An integrated investigation of these biological analyses with mechanical data should improve the design process of a new product. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2045-2052, 2017.

Hernia fibroblasts lack beta-estradiol-induced alterations of collagen gene expression.

BACKGROUND: Estrogens are reported to increase type I and type III collagen deposition and to regulate Metalloproteinase 2 (MMP-2) expression. These proteins are reported to be dysregulated in incisional hernia formation resulting in a significantly decreased type I to III ratio. We aimed to evaluate the beta-estradiol mediated regulation of type I and type III collagen genes as well as MMP-2 gene expression in fibroblasts derived from patients with or without history of recurrent incisional hernia disease. We compared primary fibroblast cultures from male/female subjects without/without incisional hernia disease. RESULTS: Incisional hernia fibroblasts (IHFs) revealed a decreased type I/III collagen mRNA ratio. Whereas fibroblasts from healthy female donors responded to beta-estradiol, type I and type III gene transcription is not affected in fibroblasts from males or affected females. Furthermore beta-estradiol had no influence on the impaired type I to III collagen ratio in fibroblasts from recurrent hernia patients. CONCLUSION: Our results suggest that beta-estradiol does not restore the imbaired balance of type I/III collagen in incisional hernia fibroblasts. Furthermore, the individual was identified as an independent factor for the beta-estradiol induced alterations of collagen gene expression. The observation of gender specific beta-estradiol-dependent changes of collagen gene expression in vitro is of significance for future studies of cellular response.

Effect of lifestyle, gender and age on collagen formation and degradation.

Historically, inappropriate lifestyle with an inadequate dietary intake of vitamin C has been associated with poor wound healing as a clinical manifestation of scurvy. In modern times, clinical evidence produced over the past few decades indicates that a modern lifestyle factor, such as smoking, together with biologic characteristics, like old age and male gender, are risk factors for abdominal wall hernia and recurrence. The pathologic pathways for these clinical observations are unclear. Yet, evidence from animal and human studies suggests that these exogenous and endogenous factors may have a negative impact on collagen metabolism, enhancing degradation and impairing formation.

The biology of hernias and the abdominal wall.

The fundamental mechanism for hernia formation is loss of the mechanical integrity of abdominal wall structural tissue that results in the inability to offset and contain intra-abdominal forces during valsalva and loading of the torso. There is evidence that genetic or systemic extracellular matrix disorders may predispose patients to hernia formation. There is also evidence that acute laparotomy wound failure leads to hernia formation and increases the risk of recurrent hernia disease. It may be that hernia formation is a heterogeneous disease, not unlike cancer, where one population of patients express an extracellular matrix defect leading to primary hernia disease, while other subsets of patients acquire a defective, chronic wound phenotype following failed laparotomy and hernia repairs. It is evident that an improved understanding of structural tissue matrix biology will lead to improved results following abdominal wall reconstructions.

Systemic and local collagen turnover in hernia patients.

BACKGROUND: Hernia formation is a multifactorial disease involving important endogenous factors possibly affected by exogenous factors. Alterations in collagen composition seem to contribute to abdominal wall hernia formation, possibly related to increased collagen breakdown. The collagen composition appears altered in fascial tissue but also in skin biopsies, suggesting that the collagen alterations are systemic. More pronounced collagen alterations are found in patients with hernia recurrences. Hypothetically, primary inguinal hernias are formed due to a systemic predisposition to altered connective tissue, whereas impaired healing influences on the development of incisional hernias and hernia recurrences. The overall objective of this thesis was to investigate the collagen turnover systemically and locally in patients with primary inguinal hernia, multiple hernias and incisional hernia. METHODS AND RESULTS: In a systematic literature review, a total of 55 original articles were reviewed evaluating connective tissue alterations in patients with abdominal wall hernias. Patients with inguinal and incisional hernias exhibit a decreased type I to III collagen ratio in fascia and skin biopsies with the most pronounced alterations found in patients with direct inguinal hernia and hernia recurrence. An increased level of MMP-2 was reported in patients with inguinal hernias. In a nationwide study from the Danish Hernia Database, 92,283 patients with an inguinal hernia repair were identified from January 1998 until June 2010. A total of 843 patients were also registered with a ventral hernia repair. Direct (OR = 1.28 [95% C.I. 1.08-1.51]) and recurrent (OR = 1.76 [95% C.I. 1.39-2.23]) inguinal hernia repairs were significantly associated with ventral hernia repair compared to indirect inguinal hernia repair after adjustment for gender, age and surgical approach. In a multivariable subgroup analysis, direct and recurrent inguinal hernia repair were associated with primary ventral hernia surgery, whereas only recurrent inguinal hernia repair was associated with secondary ventral hernia surgery. In a cohort of 305 patients followed up a median of 3.7 years after emergency or elective laparotomy, a total of 79 patients were identified with an incisional hernia. Patients were subgrouped based on the identified risk factors male gender and smoking in eight groups with nine patients in each. Pooled serum samples were screened for MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-12, MMP-13, TIMP-1, TIMP-2, and TIMP-4 with a multiarray and zymography. The screening indicated differences in MMP-9 and TIMP-1, which were measured in serum samples of the whole patient cohort with ELISA. There were no differences in systemic MMP-9 and TIMP-1 levels between patients with and without incisional hernia. Patients were enrolled consecutively in four groups: 1) patients undergoing elective laparoscopic cholecystectomy without hernias (N = 18), patients operated on for 2) primary unilateral inguinal hernia (N = 17), 3) multiple hernias defined as three or more primary hernias (N = 21) and 4) incisional hernia (N = 25). Venous blood was collected preoperatively. Pro-MMP-2 and pro-MMP-9 were measured in serum by gelatine zymography, and there were no significant differences between hernia patients and controls. Furthermore, serological biomarkers for type I, III, IV and V collagen turnover were measured in serum by solid-phase competitive immunoassays. In patients with inguinal hernia, type III and V collagen turnover were significantly decreased, whereas type IV collagen turnover was significantly increased. In incisional hernia patients, type V collagen turnover was significantly decreased, whereas type IV collagen turnover was significantly increased. Type IV collagen turnover seem to predict the presence of both inguinal and incisional hernia. An ePTFE tube was implanted perioperatively in all four patient groups and explanted on the tenth post-operative day. Newly synthesized granulation tissue in the ePFTE tube represents the patients' wound healing potential. Hydroxyproline levels were measured as a marker for total collagen deposition and were unaltered in hernia patients compared to controls. Pro-MMP-2 and pro-MMP-9 levels in the PTFE tubes did not differ between hernia patients and controls. A fascia transversalis biopsy was excised perioperatively in all four patient groups. There were no significant differences between hernia patients and controls in total collagen concentration or morphology of the fascia transversalis. CONCLUSIONS: Direct and recurrent inguinal hernia repair are associated with ventral hernia repair, suggesting a systemic predisposition to the hernia disease. MMPs are not suitable as serum biomarkers for inguinal or incisional hernia disease. Serum biomarkers for collagen turnover are altered in both inguinal and incisional hernia patients; specifically markers for type IV collagen turnover seem to predict the presence of hernias.  A systemic biomarker predicting hernia disease would be useful to plan a tailored surgical strategy for the individual patient.

Skin as marker for collagen type I/III ratio in abdominal wall fascia.

PURPOSE: An altered collagen metabolism could play an important role in hernia development. This study compared collagen type I/III ratio and organisation between hernia and control patients, and analysed the correlation in collagen type I/III ratio between skin and abdominal wall fascia. METHODS: Collagen organisation was analysed in Haematoxylin-Eosin sections of anterior rectus sheath fascia, and collagen type I/III ratio, by crosspolarisation microscopy, in Sirius-Red sections of skin and anterior rectus sheath fascia, of 19 control, 10 primary inguinal, 10 recurrent inguinal, 13 primary incisional and 8 recurrent incisional hernia patients. RESULTS: Compared to control patients [7.2 (IQR = 6.8-7.7) and 7.2 (IQR = 5.8-7.9)], collagen type I/III ratio was significantly lower in skin and anterior rectus sheath fascia of primary inguinal [5.2 (IQR = 3.8-6.3) and 4.2 (IQR = 3.8-4.7)], recurrent inguinal [3.2 (IQR = 3.1-3.6) and 3.3 (IQR = 3-3.7)], primary incisional [3.5 (IQR = 3-3.9) and 3.4 (IQR = 3.3-3.6)] and recurrent incisional hernia [3.2 (IQR = 3.1-3.9) and 3.2 (IQR = 2.9-3.2)] patients; also incisional and recurrent inguinal hernia had lower ratio than primary inguinal hernia patients. Furthermore, collagen type I/III ratio was significantly correlated (r = 0.81; P < 0.001) between skin and anterior rectus sheath fascia. Finally, collagen organisation was comparable between hernia and control patients. CONCLUSIONS: Furthermore, in both skin and abdominal wall fascia of hernia patients, collagen type I/III ratio was lower compared to control patients, with more pronounced abnormalities in incisional and recurrent inguinal hernia patients. Importantly, collagen type I/III ratio in skin was representative for that in abdominal wall fascia.

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.

A preclinical evaluation of alternative synthetic biomaterials for fascial defect repair using a rat abdominal hernia model.

INTRODUCTION: Fascial defects are a common problem in the abdominal wall and in the vagina leading to hernia or pelvic organ prolapse that requires mesh enhancement to reduce operation failure. However, the long-term outcome of synthetic mesh surgery may be unsatisfactory due to post-surgical complications. We hypothesized that mesh fabricated from alternative synthetic polymers may evoke a different tissue response, and provide more appropriate mechanical properties for hernia repair. Our aim was to compare the in vivo biocompatibility of new synthetic meshes with a commercial mesh. METHODS: We have fabricated 3 new warp-knitted synthetic meshes from different polymers with different tensile properties polyetheretherketone (PEEK), polyamide (PA) and a composite, gelatin coated PA (PA+G). The rat abdominal hernia model was used to implant the meshes (25 × 35 mm, n = 24/ group). After 7, 30, 60, 90 days tissues were explanted for immunohistochemical assessment of foreign body reaction and tissue integration, using CD31, CD45, CD68, alpha-SMA antibodies. The images were analysed using an image analysis software program. Biomechanical properties were uniaxially evaluated using an Instron Tensile® Tester. RESULTS: This study showed that the new meshes induced complex differences in the type of foreign body reaction over the time course of implantation. The PA, and particularly the composite PA+G meshes, evoked a milder early inflammatory response, and macrophages were apparent throughout the time course. Our meshes led to better tissue integration and new collagen deposition, particularly with the PA+G meshes, as well as greater and sustained neovascularisation compared with the PP meshes. CONCLUSION: PA, PA+G and PEEK appear to be well tolerated and are biocompatible, evoking an overlapping and different host tissue response with time that might convey mechanical variations in the healing tissue. These new meshes comprising different polymers may provide an alternative option for future treatment of fascial defects.

Impact of mesh positioning on foreign body reaction and collagenous ingrowth in a rabbit model of open incisional hernia repair.

BACKGROUND: Incisional hernia remains as one of the most common surgical complications. Different mesh techniques are used in 75-80% of hernia repair. The aim of this study was to evaluate the dependence of mesh positioning and the type of mesh implanted on foreign body reaction and collagenous ingrowth. MATERIALS AND METHODS: In 24 male Chinchilla rabbits, an incisional hernia repair was performed with mesh reinforcement either by sublay (n = 12) or by onlay technique (n = 12). In each group, two different types of mesh prosthesis were investigated: polypropylene (PP, Prolene) and polypropylene-polyglecaprone 25 composite (PP-PG, UltraPro). On postoperative day 60, the inflammatory and connective tissue formation was characterised by measuring the diameter of inner cellular infiltrate and outer fibrous capsule of the foreign body granuloma, and by verifying the collagen type I/III ratio. Furthermore, the expression of matrix metalloproteinase-2 (MMP-2) was analysed. RESULTS: Microscopic investigation of the mesh/host-tissue interface showed typical formation of foreign body granuloma. The diameters of the inner part of the foreign body granuloma representing the amount of inflammatory cell infiltrate were significantly increased in the PP mesh compared to the PP-PG mesh, both in the sublay group (PP 13.1 +/- 1.21 microm vs. PP-PG 11.7 +/- 0.34 microm; P = 0.026) and in the onlay group (PP 13.1 +/- 1.24 microm vs. PP-PG 11.2 +/- 0.55 microm; P = 0.009). The diameter of the fibrous capsule as the outer ring of the granuloma was significantly increased when investigating the PP mesh in sublay position (29.5 +/- 1.12 microm) compared to the PP mesh in onlay position (27.9 +/- 0.73 microm) (P = 0.026). Investigating the quality of perifilamentary collagen deposition expressed as collagen type I/III ratio, the sublay group showed significantly elevated values compared to the onlay group (PP sublay 3.1 +/- 0.18 vs. PP onlay 2.4 +/- 0.41; P = 0.004) (PP-PG sublay 3.5 +/- 0.34 vs. PP-PG onlay 2.6 +/- 0.13; P = 0.002). The analysis of MMP-2 expression revealed no significant differences. CONCLUSION: The beneficial results of mesh reinforcement in the sublay technique might be due to a superior quality of postoperative connective tissue formation. Mesh incorporation, irrespective of positioning, is favourable in low-weight, large, porous mesh material represented by a reduced inflammatory part of the foreign body granuloma.