Simulation of vaginal uterosacral ligament suspension damage, mimicking a mesh-augmented apical prolapse repair.

Synthetic implants were used for repair of anterior compartment prolapses, which can be caused by direct trauma resulting in damaged pelvic structures. The mechanical properties of these implants may cause complications, namely erosion of the mesh through the vagina. In this study, we evaluated, by modeling, the behavior of implants, during Valsalva maneuver, used to replace damaged uterosacral ligaments (USLs), mimicking a sacrocolpopexy repair. For this purpose, two synthetic implants (A®, for prolapse repair and B®, for Hernia repair) were uniaxially tested, and the mechanical properties obtained were incorporated in the computational models of the implants. The computational model for the implant was incorporated into the model of the female pelvic cavity, in order to mimic the USLs after its total rupture and with 90% and 50% impairment. The total rupture and impairments of the USLs, caused a variation of the supero-inferior displacement and displacement magnitude of the vagina, with higher values for the total rupture. With total rupture of the USLs, when compared to healthy USLs, supero-inferior displacement and displacement magnitude of the vagina increased by 4.98 mm (7.69 mm vs 12.67 mm) and 6.62 mm (9.38 mm vs 16.00 mm), respectively. After implantation (A® and B®) a reduction of the supero-inferior displacements of the anterior vaginal wall occurred, to values found in the case of the model without any impairment or rupture of the ligaments. The simulation was able to mimic the biomechanical response of the USLs, in response to different implants stiffnesses, which can be used in the development of novel meshes.

Melt Electrospinning Writing of Mesh Implants for Pelvic Organ Prolapse Repair.

Over the past decade, melt electrospinning writing has attracted renewed attention. When combined with three-dimensional (3D) printing capabilities, complex 3D structures can be produced, from ultrafine fibers in the absence of toxic solvents, making it particularly attractive to fabricate customized scaffolds and implants for medical applications. This research aimed to develop novel less stiff vaginal mesh implants for pelvic organ prolapse (POP) repair, matching the physiological biomechanics of vaginal tissues. The main objectives, to attain that goal, were: development of a melt electrospinning writing prototype, with additive manufacturing capability, to produce complex structures from micrometer scale fibers, in a direct 3D printing mode; and design and validate new concepts of biodegradable meshes/scaffolds with new geometries, for POP repair. The melt electrospinning writing prototype was built based on different modules. Biodegradable polycaprolactone was used to produce novel implants: three geometries and two fiber configurations were employed. The commercially available Restorelle® (Coloplast) mesh was used as a benchmark. Printed implants were analyzed via scanning electron microscopy (SEM) and uniaxial tensile testing. The SEM images showed that the geometry is generally well produced; however, some minor deviations are visible due to charge interactions. The tensile test results indicated that, regardless of the geometry, the samples showed an elastic behavior for smaller displacements; aplastic behavior dominates later stages. In the physiological range of deformation, the novel meshes (80 µm fiber diameter) matched the tissue properties (p > 0.05). The Restorelle mesh was significantly stiffer than vaginal tissue (p < 0.05) and novel meshes. The precision of the various geometrical patterns and fiber diameters produced highlights the success of the designed and built prototype equipment. Results showed that the biodegradable meshes produced are biomechanically more compatible with native tissue than commercial implants.

The ewe as an animal model of vaginal atrophy and vaginal Er:YAG laser application.

OBJECTIVE: In sheep of reproductive age, we aimed to document decrease in epithelial thickness, glycogen amount, and other vaginal changes after castration and the effect of Er:YAG laser as used clinically. METHODS: On day 0, 16 sheep underwent ovariectomy. They were randomized to sham or three vaginal Er:YAG laser applications at monthly intervals. Primary outcome was vaginal epithelial thickness (d60, d71, d73, d77, and d160). Secondary outcomes included indicators of atrophy (vaginal health index = VHI), pH, cytology, morphology at the above time points, microcirculation focal depth (FD; d70 and d160), and at sacrifice (d160) vaginal dimensions and active and passive biomechanical testing. RESULTS: Menopausal changes between 60 and 160 days after ovariectomy included a progressive decrease in epithelial thickness, in VHI, FD, glycogen, elastin content and vasculature, and an increase in pH and collagen content. In lasered animals, the first day a few white macroscopic foci were visible and an increase in pH was measured. Both disappeared within 3 days. Seven days after laser the epithelial thickness increased. At sacrifice (d160), there were no differences between sham and laser group in vaginal dimensions, morphometry, mitotic and apoptotic activity, active contractility, vaginal compliance, except for a lower blood vessel density in the lamina propria of the midvagina in the laser group. CONCLUSIONS: In reproductive sheep, ovariectomy induces vaginal atrophy evidenced in different outcome measurements. Vaginal Er:YAG laser induced visual impact, a short-term increase in epithelial thickness yet no long-term changes compared to sham therapy in menopausal controls.

Video Summary:http://links.lww.com/MENO/A672.

Functional supramolecular bioactivated electrospun mesh improves tissue ingrowth in experimental abdominal wall reconstruction in rats.

Development of biomaterials for hernia and pelvic organ prolapse (POP) repair is encouraged because of high local complication rates with current materials. Therefore, we aimed to develop a functionalized electrospun mesh that promotes tissue ingrowth and provides adequate mechanical strength and compliance during degradation. We describe the in vivo function of a new supramolecular bioactivated polycarbonate (PC) material based on fourfold hydrogen bonding ureidopyrimidinone (UPy) units (UPy-PC). The UPy-PC material was functionalized with UPy-modified cyclic arginine-glycine-aspartic acid (cRGD) peptide additives. Morphometric analysis of the musculofascial content during wound healing showed that cRGD functionalization promotes myogenesis with inhibition of collagen deposition at 14 days. It also prevents muscle atrophy at 90 days and exerts an immunomodulatory effect on infiltrating macrophages at 14 days and foreign body giant cell formation at 14 and 90 days. Additionally, the bioactivated material promotes neovascularization and connective tissue ingrowth. Supramolecular cRGD-bioactivation of UPy-PC-meshes promotes integration of the implant, accelerates tissue ingrowth and reduces scar formation, resulting in physiological neotissue formation when used for abdominal wall reconstruction in the rat hernia model. Moreover, cRGD-bioactivation prevents muscle atrophy and modulates the inflammatory response. Our results provide a promising outlook towards a new type of biomaterial for the treatment of hernia and POP. STATEMENT OF SIGNIFICANCE: Development of biomaterials for hernia and pelvic organ prolapse (POP) repair is encouraged because of high local complication rates with current materials. Ureidopyrimidinone-polycarbonate is a elastomeric and biodegradable electrospun mesh, which could mimic physiological compliance. The UPy-PC material was functionalized with UPy-modified cyclic arginine-glycine-aspartic acid (cRGD) peptide additives. Supramolecular cRGD-bioactivation of UPy-PC-meshes promotes integration of the implant, accelerates tissue ingrowth and reduces scar formation, resulting in physiological neotissue formation when used for abdominal wall reconstruction in rat hernia model. Moreover, cRGD-bioactivation prevents muscle atrophy and modulates the inflammatory response. These data provide a promising outlook towards a new type of biomaterial for the treatment of hernia and POP.

Assessment of Electrospun and Ultra-lightweight Polypropylene Meshes in the Sheep Model for Vaginal Surgery.

BACKGROUND: There is an urgent need to develop better materials to provide anatomical support to the pelvic floor without compromising its function. OBJECTIVE: Our aim was to assess outcomes after simulated vaginal prolapse repair in a sheep model using three different materials: (1) ultra-lightweight polypropylene (PP) non-degradable textile (Restorelle) mesh, (2) electrospun biodegradable ureidopyrimidinone-polycarbonate (UPy-PC), and (3) electrospun non-degradable polyurethane (PU) mesh in comparison with simulated native tissue repair (NTR). These implants may reduce implant-related complications and avoid vaginal function loss. DESIGN, SETTING, AND PARTICIPANTS: A controlled trial was performed involving 48 ewes that underwent NTR or mesh repair with PP, UPy-PC, or PU meshes (n=12/group). Explants were examined 60 and 180 d (six per group) post-implantation. INTERVENTION: Posterior rectovaginal dissection, NTR, or mesh repair. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Implant-related complications, vaginal contractility, compliance, and host response were assessed. Power calculation and analysis of variance testing were used to enable comparison between the four groups. RESULTS: There were no visible implant-related complications. None of the implants compromised vaginal wall contractility, and passive biomechanical properties were similar to those after NTR. Shrinkage over the surgery area was around 35% for NTR and all mesh-augmented repairs. All materials were integrated well with similar connective tissue composition, vascularization, and innervation. The inflammatory response was mild with electrospun implants, inducing both more macrophages yet with relatively more type 2 macrophages present at an early stage than the PP mesh. CONCLUSIONS: Three very different materials were all well tolerated in the sheep vagina. Biomechanical findings were similar for all mesh-augmented repair and NTR. Constructs induced slightly different mid-term inflammatory profiles. PATIENT SUMMARY: Product innovation is needed to reduce implant-related complications. We tested two novel implants, electrospun and an ultra-lightweight polypropylene textile mesh, in a physiologically relevant model for vaginal surgery. All gave encouraging outcomes.

Predicting the mechanical response of the vaginal wall in ball burst tests based on histology.

A histologically motivated (HM) coefficient that establishes a link between tissue's microstructure and material model through histological data is used in the prediction of the mechanical properties of vaginal tissue that is subjected to multiaxial loading conditions. Therefore, the material parameters were based on an HM coefficient obtained from tensile testing and histological data of comparable tissues. Uniaxial tensile test data and histological data were collected from three groups of sheep at different time points in their life cycle, including virgins, pregnant, and parous ewes. From this data, a correlation between material parameters and histological data was obtained. Spherical indentation (ball burst [BB]) tests were then performed in specimens with similar tissue structure. The histological data of these samples were used in conjunction with the correlations already established for the uniaxial samples data, to define the material parameters of the BB samples. Mechanical properties of the BB specimens were predicted through basic histology and using finite element modeling (FEM) simulations, without direct mechanical measurements. The predicted force and displacement values of the FEM simulation displayed a good correlation with the experimental (BB) testing results. No fitting of the BB results was performed. In this way, the use of uniaxial tests coupled with useful histological information offers a promising approach to predicting macroscopic material behavior under multiaxial loading conditions in biomechanics.

The histological microstructure and in vitro mechanical properties of pregnant and postmenopausal ewe perineal body.

OBJECTIVE: The mechanical properties and microstructure of the perineal body are important for the improvement of numerical models of pelvic organs. We determined the mechanical parameters and volume fractions of the ewe perineal body as an animal model. METHODS: The 39 specimens of 13 pregnant swifter ewes delivering by cesarean section (aged 2 years, weight 61.2 ±â€Š6.2 kg (mean ±â€Šstandard deviation) and 24 specimens of 8 postmenopausal swifter ewes 150 days after surgical ovariectomy (aged 7 years, 58.6 ±â€Š4.6 kg)) were loaded uniaxially to determine Young's moduli of elasticity in the small (E0) and large (E1) deformation regions, and ultimate stresses and strains. The 63 adjacent tissue samples were processed histologically to assess volume fractions of smooth and skeletal muscle, adipose cells, elastin, and type I collagen using a stereological point testing grid. We compared the structural and mechanical differences along the ewe perineal body, and between pregnant and postmenopausal groups. RESULTS: The pregnant/postmenopausal perineal body was composed of smooth muscle (12/14%; median), skeletal muscle (12/16%), collagen (10/23%), elastin (8/7%), and adipose cells (6/6%). The E0 was 37/11 kPa (median), E1 was 0.97/1.04 MPa, ultimate stress was 0.55/0.59 MPa, and ultimate strain was 0.90/0.87 for pregnant/postmenopausal perineal body. The perineal body showed a structural and mechanical stability across the sites. The pregnant ewes had a higher amount of skeletal muscle, higher E0, and a less amount of collagen when compared with postmenopausal ewes. CONCLUSIONS: The data can be used as input for models simulating vaginal delivery, pelvic floor prolapsed, or dysfunction.

Biomechanical Behaviour and Biocompatibility of Ureidopyrimidinone-Polycarbonate Electrospun and Polypropylene Meshes in a Hernia Repair in Rabbits.

Although mesh use has significantly improved the outcomes of hernia and pelvic organ prolapse repair, long-term recurrence rates remain unacceptably high. We aim to determine the in vivo degradation and functional outcome of reconstructed abdominal wall defects, using slowly degradable electrospun ureidopyrimidinone moieties incorporated into a polycarbonate backbone (UPy-PC) implant compared to an ultra-lightweight polypropylene (PP) textile mesh with high pore stability. Twenty four New-Zealand rabbits were implanted with UPy-PC or PP to either reinforce a primary fascial defect repair or to cover (referred to as gap bridging) a full-thickness abdominal wall defect. Explants were harvested at 30, 90 and 180 days. The primary outcome measure was uniaxial tensiometry. Secondary outcomes were the recurrence of herniation, morphometry for musculofascial tissue characteristics, inflammatory response and neovascularization. PP explants compromised physiological abdominal wall compliance from 90 days onwards and UPy-PC from 180 days. UPy-PC meshes induced a more vigorous inflammatory response than PP at all time points. We observed progressively more signs of muscle atrophy and intramuscular fatty infiltration in the entire explant area for both mesh types. UPy-PC implants are replaced by a connective tissue stiff enough to prevent abdominal wall herniation in two-thirds of the gap-bridged full-thickness abdominal wall defects. However, in one-third there was sub-clinical herniation. The novel electrospun material did slightly better than the textile PP yet outcomes were still suboptimal. Further research should investigate what drives muscular atrophy, and whether novel polymers would eventually generate a physiological neotissue and can prevent failure and/or avoid collateral damage.

Morphological and Functional Changes in the Vagina following Critical Lifespan Events in the Ewe.

BACKGROUND/AIMS: The ewe is increasingly being used as an animal model for pelvic floor disorders. The aim was to further characterize changes in the vaginal properties during its entire lifespan. METHODS: Vaginal tissues were collected at different stages of reproductive life (neonatal, prepubescence, nulliparous, primiparous, multiparous, and menopausal; ≥6 ewes/group). Vaginal size, as well as active and passive biomechanics, was measured. Microscopy included thickness of glycogen, epithelium, lamina propria and muscularis thickness, densities of collagen, elastin, smooth muscle, and nerves. RESULTS: Vaginal dimensions increase during adolescence, peak at reproductive levels, and decrease sharply after ovariectomy. One year after first delivery, the distal vagina gets more compliant, yet this is reversed later in life. The thickness of glycogen staining epithelial layers changed with puberty and menopause. The epithelium was markedly thicker after multiple deliveries. The thickness of lamina propria and muscularis increased in puberty and in nulliparous. Semi-quantitative collagen assessment demonstrated a lower collagen and higher elastin content after first and multiple deliveries. CONCLUSION: The changes in the ovine vaginal wall during representative moments of her lifespan parallel those observed in women.

Linking hyperelastic theoretical models and experimental data of vaginal tissue through histological data.

Mechanical characterization of living tissues and computer-based simulations related to medical issues, has become increasingly important to improve diagnostic processes and treatments evaluation. This work proposes a link between the mechanical testing and the material model predictions through histological data of vaginal tissue. Histological data was used to link tensile testing experiments with material-dependent parameters; the approach was adequate to capture the nonlinear response of ovine vaginal tissue over a large strain range. The experimental data obtained on a previous study, has two main components: tensile testing and histological analysis of the ovine vaginal tissue. Uniaxial tensile test data and histological data were collected from three sheep groups: virgins, pregnant and parous. The distal part of vaginal wall was selected since it is prone to tears induced by vaginal delivery. The HGO (Holzapfel-Gasser-Ogden) model parameters were fitted using a stochastic approach, namely the Simple Genetic Algorithm (SGA). The SGA was able to fit the experimental data successfully (R2 > 0.986). The dimensionless coefficient ξ, was highly correlated with histological data. The ratio was seen to increase linearly with increasing collagen content. Coefficient ξ brings a new way of interpreting and understanding experimental data; it connects the nonlinear mechanical behaviour (tensile test) with tissue's morphology (histology). It can be used as an 'inverse' (approximate) method to estimate the mechanical properties without direct experimental measurements, through basic histology. In this context, the proposed methodology appears very promising in estimating the response of the tissue via histological information.

The effect of consecutive pregnancies on the ovine pelvic soft tissues: Link between biomechanical and histological components.

BACKGROUND: Pelvic organ prolapse, various types of incontinence (urinary incontinence, defecatory dysfunction), chronic cystourethritis, and sexual dysfunctions remain between the most common disorders in urogynecology. Currently, it is believed that the nature and number of births plays a major role in their development. Moreover, after these events, pelvic floor tissues may not recover to their original statuses. The close anatomical relationship among the vaginal wall, bladder and rectum often contribute to the emergence of anatomical-functional failure of adjacent organs and systems. BASIC PROCEDURES: The aim of this study was to investigate the effect of consecutive pregnancies on pelvic floor soft tissues, conducting biomechanical and histological analysis. Fifteen Swifter ewes: virgins, parous and pregnant were used. Samples, for uniaxial tension tests and histological analysis, were cut out from fresh tissue. A description of the mechanical properties of native tissue was obtained from the stress-strain curve. Histological samples were stained with Miller's Elastica staining and analyzed using ImageJ software. Collagen, elastin, and smooth muscle contents (%) were analyzed along the full wall thickness of the selected organs. The links between mechanical properties of the soft tissues and histological parameters were analyzed. MAIN FINDINGS: Mechanically, vaginal wall tissue and cervix of pregnant sheep were more compliant. In contrast, bladder and rectum became stiffer and had the highest total collagen content. Parous sheep rectum and bladder were stiffer, compared to virgin sheep. PRINCIPAL CONCLUSIONS: Tensile strength appears to be linked to total collagen content. Elastin and smooth muscle show a direct influence on tissue compliance.

Experimental reconstruction of an abdominal wall defect with electrospun polycaprolactone-ureidopyrimidinone mesh conserves compliance yet may have insufficient strength.

PURPOSE: Electrospun meshes mimic the extracellular matrix, which may improve their integration. We aimed to compare polycaprolactone (PCL) modified with ureidopyrimidinone (UPy) electrospun meshes with ultra-lightweight polypropylene (PP; Restorelle) reference textile meshes for in vivo compliance. We chose UPy-PCL because we have shown it does not compromise biomechanical properties of native tissue, and because it potentially can be bioactivated. METHODS: We performed ex vivo biomechanical cyclic loading in wet conditions and in vivo overlay of full-thickness abdominal wall defects in rats and rabbits. Animals were sacrificed at 7, 42 and 54 days (rats; n = 6/group) and 30 and 90 days (rabbits; n = 3/group). Outcomes were herniation, mesh degradation and mesh dimensions, explant compliance and histology. High failure rates prompted us to provide additional material strength by increasing fiber diameter and mesh thickness, which was further tested in rabbits as a biomechanically more challenging model. RESULTS: Compliance was tested in animals without herniation. In both species, UPy-PCL-explants were as compliant as native tissue. In rats, PP-explants were stiffer. Contraction was similar in UPy-PCL and PP-explants. However, UPy-PCL-meshes macroscopically degraded from 30 days onwards, coinciding with herniation in up to half of animals. Increased fiber and mesh thickness did not improve outcome. Degradation of UPy-PCL is associated with an abundance of foreign body giant cells until UPy-PCL disappears. CONCLUSION: Abdominal wall reconstruction with electrospun UPy-PCL meshes failed in 50%. Degradation coincided with a transient vigorous foreign body reaction. Non-failing UPy-PCL-explants were as compliant as native tissue. Despite that, the high failure rate forces us to explore electrospun meshes based on other polymers.

Providing direction improves function: Comparison of a radial pore-orientated acellular collagen scaffold to clinical alternatives in a surgically induced rabbit diaphragmatic tissue defect model.

Gore-Tex® is a widely used durable patch for repair of congenital diaphragmatic defects yet may result in complications. We compared Gore-Tex with a composite of a radial pore-orientated collagen scaffold (RP-Composite) and clinically used porcine small intestinal submucosa (SIS; Surgisis®) in a rabbit model for diaphragmatic hernia. The growing rabbit mimics the rapid rib cage growth and reherniation rates seen in children. We created and immediately repaired left hemidiaphragmatic defects in 6-week-old rabbits with Gore-Tex, SIS, and an RP-Composite scaffold. An additional group of rabbits had a sham operation. At 90 days, survivors more than doubled in weight. We observed few reherniations or eventrations in Gore-Tex (17%) and RP-Composite (22%) implanted animals. However, SIS failed in all rabbits. Maximum transdiaphragmatic pressure was lower in Gore-Tex (71%) than RP-Composite implanted animals (112%) or sham (134%). Gore-Tex repairs were less compliant than RP-Composite, which behaved as sham diaphragm (p < 0.01). RP-Composite induced less foreign body giant cell reaction than Gore-Tex (p < 0.05) with more collagen deposition (p < 0.001), although there was a tendency for the scaffold to calcify. Unlike Gore-Tex, the compliance of diaphragms reconstructed with RP-Composite scaffolds were comparable with native diaphragm, whereas reherniation rates and transdiaphragmatic pressure measurements were similar.

In vitro study of the mechanical performance of hernia mesh under cyclic loading.

The use of prostheses for hernia surgery, made from synthetic polymers may lead to development of postoperative complications. The reason for this can be the mismatch of the mechanical properties of meshes and the loads acting on them. The aim of this work was to investigate the behavior of 3 different hernia meshes under in vitro simulated physiological conditions followed by cyclic loadings. Meshes, Ultrapro (poliglecaprone and polypropylene), Dynamesh (polyvinylidenefluoride) and Surgipro (polypropylene) were selected. For in vitro degradation test, samples were kept in alkaline and acid mediums at 37 °C during 42 and 90 days and analyzed in terms of their weight loss and thickness changes. This was followed by cyclic loading in three increasing load stages. The greatest weight loss and thickness reduction were suffered by Ultrapro mesh. The mesh showed pH independent characteristics. Surgipro mesh had pH independent behavior due to the degradation process, with slight weight loss and thickness reduction. The degradation mechanism of Dynamesh is highly dependent on the pH, with acid surrounding medium acting as a degradation catalyst. Mechanical hysteresis was observed in all three meshes. The larger deformations occurred in Surgipro (25%); necking phenomenon was also observed. The deformation of Dynamesh was 22%, the mesh unweaves under applied load and was unable to withstand the third period of cyclic loads. Ultrapro mesh exhibits the lowest level of deformation (10%). Despite the different compositions and architectures of the meshes, all three underwent permanent plastic deformation, which will induce decreased mesh flexibility over time.

In vivo documentation of shape and position changes of MRI-visible mesh placed in rectovaginal septum.

BACKGROUND AND OBJECTIVE: Large deformations in synthetic meshes used in pelvic organ prolapse surgery may lead to suboptimal support for the underlying tissue, graft-related complications as well as recurrence. Our aim was to quantify in vivo longitudinal changes in mesh shape and geometry in a large animal model. We compare two commonly used mesh shapes, armed and flat, that are differently affixed. The secondary outcomes were active and passive biomechanical properties. METHODS: A total of 18 animals were used. Six each were implanted with either an arm mesh, a flat mesh or underwent a sham surgery. PVDF meshes loaded with Fe2O3 were used to facilitate their visualization in vivo. MR images were taken at 2, 14 and 60 days after implantation and 3D models of the meshes were created at each time point. We calculate the Effective Surface Area (ESA), i.e. the support that the mesh provides to the underlying tissue using custom developed techniques. Longitudinal changes in the mesh shape were studied by comparing the respective 3D models using part comparison analyses. The root means square difference (RMSD) and the modified Hausdorff distance (MHD) were calculated to obtain an objective value for the part comparisons. Wall thickness maps were produced on 3D models. Mesh arm length and their ellipticity profiles were also evaluated. Active and passive biomechanical tests on vaginal tissue overlaying the mesh were conducted using a contractility assay and a uniaxial loading protocol. RESULTS: MR images of 5 animals in each group were used for longitudinal comparison. Compared to the initial implant size, there was an immediate drop in the ESA measurement at day 2 of almost 32.22 [7.06] % (median [IQR]) for flat meshes, and by 17.59 [6.50] % for arm meshes. After 14 days, the reduction in area was 41.84 [14.89] % and 27.18 [20.44] %, and at day 60 it was 36.61 [6.64] % and 26.43 [14.56] % for the flat and armed meshes respectively. The reduction in area in the two groups was different between the two groups only day 14 (p = 0.046). The ellipticity of the arms was 0.81 [0.08] (median [IQR]) and there was no significant change in the ellipticity profiles over time. The mesh arm length did not change significantly over time. The part comparison showed a maximum difference of 4.26 [3.29] mm in 3D models according to the MHD measure, which is clinically not relevant. Comparison of high thickness areas on the thickness maps correlated well with the areas of mesh folding in the arm mesh group observed during postmortem dissection. Thickness maps did not help us understand why the flat meshes had a reduction in support area. The comfort zone stiffness of the flat mesh and of the central part of the arm mesh were 2.4 fold and 4.5 times stiffer compared to sham groups, respectively. The arms were 36% stiffer than the central part of the mesh. The comfort zone length of the sham group was 46% longer than the flat mesh group (p = 0.027) and 59% longer than that of the central part of the arm mesh (p = 0.005). There was no significant difference in vaginal contractile forces generated in samples from the arm, flat mesh, and sham groups. CONCLUSIONS: This is a first longitudinal study observing deformations in vaginally implanted synthetic meshes in a large animal model. A novel methodology is presented to calculate the area of the vaginal tissue effectively supported by the mesh implant. Immediately post-operatively, a reduction in 32% and 17% was noted, which remained stable over the 60 following days of observation. We use thickness maps to analyze the cause of this dramatic immediate reduction. In the armed mesh we found it to be mesh folding at the interface between the arms and central part. For the flat mesh we suggest that pore aggregation during suturing.

Physiologic musculofascial compliance following reinforcement with electrospun polycaprolactone-ureidopyrimidinone mesh in a rat model.

PURPOSE: Electrospun meshes may be considered as substitutes to textile polypropylene implants. We compared the host response and biomechanical properties of the rat abdominal wall following reinforcement with either polycaprolactone (PCL) modified with ureidopyrimidinone-motifs (UPy) or polypropylene mesh. METHODS: First we measured the response to cyclic uniaxial load within the physiological range both dry (room temperature) and wet (body temperature). 36 rats underwent primary repair of a full-thickness abdominal wall defect with a polypropylene suture (native tissue repair), or reinforced with either UPy-PCL or ultra-light weight polypropylene mesh (n = 12/group). Sacrifice was at 7 and 42 days. Outcomes were compliance of explants, mesh dimensions, graft related complications and semi-quantitative assessment of inflammatory cell (sub) types, neovascularization and remodeling. RESULTS: Dry UPy-PCL implants are less stiff than polypropylene, both are more compliant in wet conditions. Polypropylene loses stiffness on cyclic loading. Both implant types were well incorporated without clinically obvious degradation or herniation. Exposure rates were similar (n = 2/12) as well as mesh contraction. There was no reinforcement at low loads, while, at higher tension, polypropylene explants were much stiffer than UPy-PCL. The latter was initially weaker yet by 42 days it had a compliance similar to native abdominal wall. There were eventually more foreign body giant cells around UPy-PCL fibers yet the amount of M1 subtype macrophages was higher than in polypropylene explants. There were less neovascularization and collagen deposition. CONCLUSION: Abdominal wall reconstruction with electrospun UPy-PCL mesh does not compromise physiologic tissue biomechanical properties, yet provokes a vivid inflammatory reaction.

Biomechanical and morphological properties of the multiparous ovine vagina and effect of subsequent pregnancy.

Pelvic floor soft tissues undergo changes during the pregnancy. However, the degree and nature of this process is not completely characterized. This study investigates the effect of subsequent pregnancy on biomechanical and structural properties of ovine vagina. Vaginal wall from virgin, pregnant (in their third pregnancy) and parous (one year after third vaginal delivery) Swifter sheep (n=5 each) was harvested. Samples for biomechanics and histology, were cut in longitudinal axis (proximal and distal regions). Outcome measurements describing Young's modulus, ultimate stress and elongation were obtained from stress-strain curves. For histology samples were stained with Miller's Elastica staining. Collagen, elastin and muscle cells and myofibroblasts contents were estimated, using image processing techniques. Statistical analyses were performed in order to determine significant differences among experimental groups. Significant regional differences were identified. The proximal vagina was stiffer than distal, irrespective the reproductive status. During the pregnancy proximal vagina become more compliant than in parous (+47.45%) or virgin sheep (+64.35%). This coincided with lower collagen (-15 to -21%), higher elastin (+30 to +60%), and more smooth muscle cells (+17 to +37%). Vaginal tissue from parous ewes was weaker than of virgins, coinciding with lower collagen (-10%), higher elastin (+50%), more smooth muscle cells (+20%). It could be proposed that after pregnancy biomechanical properties of vagina do not recover to those of virgins. Since elastin has a significant influence on the compliance of soft tissues and collagen is the main "actor" regarding strength, histological analysis performed in this study justifies the mechanical behavior observed.

Comparative Anatomy of the Ovine and Female Pelvis.

BACKGROUND: Pelvic organ prolapse affects half of vaginally parous women. Several animal models are used to study its pathophysiology and treatment. Sheep are interesting because they develop spontaneously prolapse with similar risk factors as women and can be used for vaginal surgery. This study describes ovine pelvis anatomy and compares it to women's pelvis to provide anatomical tools for translational researchers. METHODS: MRI, pelvic dissections, and histology were used for detailed macro- and microscopic analysis of relevant anatomical structures in 6 nulliparous ewes. RESULTS: Although sheep are quadrupeds, the gross and microscopic anatomies are similar to the female pelvis. Principal differences are the shape and its orientation, the absence of the sacrospinous ligament and the internal obturator. The levator ani (except for the puborectalis) and the coccygeus muscle are present, yet the latter is more developed - coinciding with the tail. The dimensions and morphology of the ovine vagina is comparable. The retropubic and the rectovaginal space are accessible transvaginally. There is a wide expression of estrogen receptors with low or absent immunoreactivity in the urethral epithelium, bladder, anus and internal anal sphincter. CONCLUSION: The ovine pelvic floor has many anatomical and ultrastructural similarities to the female pelvic floor.

Biomechanical properties of breast tissue, a state-of-the-art review.

This paper reviews the existing literature on the tests used to determine the mechanical properties of women breast tissues (fat, glandular and tumour tissue) as well as the different values of these properties. The knowledge of the mechanical properties of breast tissue is important for cancer detection, study and planning of surgical procedures such as surgical breast reconstruction using pre-surgical methods and improving the interpretation of clinical tests. Based on the data collected from the analysed studies, some important conclusions were achieved: (1) the Young's modulus of breast tissues is highly dependent on the tissue preload compression level, and (2) the results of these studies clearly indicate a wide variation in moduli not only among different types of tissue but also within each type of tissue. These differences were most evident in normal fat and fibroglandular tissues.

Thrombin Generation by Fetoscopic Trauma to the Fetal Membranes: An in vivo and in vitro Study.

OBJECTIVE: We first aimed to investigate in vivo thrombin generation induced by fetoscopy, and second we used term membrane explants for measurement of thrombin generation, thrombin receptor location and induction of selected matrix metalloproteinases (MMPs) in tissue culture. MATERIALS AND METHODS: In vivo study (37 cases): samples of amniotic fluid were taken at the beginning and end of fetoscopy (mean gestational age 26.7 weeks) and analyzed by ELISA for thrombin-antithrombin complexes. In vitro study: fetal membranes were put in culture and punctured for measurement of thrombin generation by calibrated automated thrombography and ELISA. Induction of MMP-9 and MMP-2 was analyzed by zymography. PAR-1 was localized by immunohistochemistry. RESULTS: No significant increase in thrombin-antithrombin was measured in amniotic fluid obtained during fetoscopy. In vitro, thrombin generation induced by needle trauma of membrane cultures is correlated to the amount of plasma. Activity of MMP-9 but not MMP-2 was elevated in cultured membranes but could not be inhibited by a thrombin inhibitor. On histology, the thrombin receptor PAR-1 was located in the chorion and decidua, but not in the amnion. DISCUSSION: Despite the influence of thrombin on punctured fetal membranes in vitro, the role of thrombin in iatrogenic preterm premature rupture of membranes is questionable.