Rita Rynkevic

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.

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.

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 womens 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.

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.

Implant shape influence on the mechanical behavior of breast implants

In the last few decades, breast reconstruction has evolved significantly due to improvement in surgical techniques and development of new materials. Safety issues of the materials are biocompatibility (especially of the gel) and bio durability of the shell. Reviewed literature indicates that biocompatibility in general is not an issue with the current generation of the breast implants. However, bio durability is. The deformation of breast prosthesis was simulated using the Finite Element Method (FEM). Elastic mechanical behaviour was considered for the silicone implant - filler and shell. The deformed geometry obtained from finite element analysis was compared with the real breast implant deformation made in laboratory. The aim of this research is to analyse the stresses and strains that occur in the breast implant shell and filler, and to analyse implant shape influence on its mechanical behaviour. This simulation is performed using the finite element package ABAQUS.

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.

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.

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.

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.Graphical abstract

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.