Comparison of Cross-Sectional Area of Pubovisceral Muscle in Nulliparous and Primiparous Women.

INTRODUCTION AND HYPOTHESIS: The main risk factor for pelvic floor disorders is vaginal delivery, which may cause levator ani muscle (LAM) injury and denervation. LAM includes pubovisceral muscle (PVM, pubococcygeus), puborectalis muscle (PRM), and iliococcygeus muscle. We hypothesize that primiparous women with low pelvic floor muscle contraction have a reduced PVM cross-sectional area (CSA) compared to nulliparous women. METHODS (SAMPLE SIZE AND STATISTICAL APPROACHES): This single-centre prospective observational study compared healthy nulliparous (n = 40) to primiparous (n = 40) women after vaginal delivery without LAM avulsion and Oxford score ≤ 3. Demographics, questionnaires (ICIQ-UI-SF, OAB-Q-SF, PISQ-12), POP-Q, Oxford score, ultrasound measurements (minimal anteroposterior and lateral diameters, hiatal area, PRM thickness, levator-urethra gap) and magnetic resonance imaging (MRI)-PVM CSA were evaluated. Normality was tested, and an appropriate test was used to compare the groups. Power calculation suggested 40 participants per group. RESULTS: The primiparous group was older, had a higher BMI, and their hiatal area on ultrasound at contraction was larger compared to the nulliparous group. The CSA of the left-sided PVM (1.15 ± 0.50 cm2) was larger compared to the right side (1.03 ± 0.50 cm2), p = 0.02 in nulliparous women. The PVM CSA of primiparous women with low Oxford score was reduced compared to nulliparous (0.87 ± 0.30 versus 1.09 ± 0.50 cm2, p = 0.006). The intra-rater reliability for PVM CSA had an ICC of 0.90 and inter-rater ICC of 0.77. CONCLUSIONS: Primiparous women after vaginal delivery with low pelvic floor contraction force had reduced PVM CSA on MRI images compared to nulliparous women.

Evaluation of the short-term host response and biomechanics of an absorbable poly-4-hydroxybutyrate scaffold in a sheep model following vaginal implantation.

OBJECTIVE: To evaluate the host- and biomechanical response to a fully absorbable poly-4-hydroxybutyrate (P4HB) scaffold in comparison with the response to polypropylene (PP) mesh. DESIGN: In vivo animal experiment. SETTING: KU Leuven Center for Surgical Technologies. POPULATION: Fourteen parous female Mule sheep. METHODS: P4HB scaffolds were surgically implanted in the posterior vaginal wall of sheep. The comparative PP mesh data were obtained from an identical study protocol performed previously. MAIN OUTCOME MEASURES: Gross necropsy, host response and biomechanical evaluation of explants, and the in vivo P4HB scaffold degradation were evaluated at 60- and 180-days post-implantation. Data are reported as mean ± standard deviation (SD) or standard error of the mean (SEM). RESULTS: Gross necropsy revealed no implant-related adverse events using P4HB scaffolds. The tensile stiffness of the P4HB explants increased at 180-days (12.498 ± 2.66 N/mm SEM [p =0.019]) as compared to 60-days (4.585 ± 1.57 N/mm) post-implantation, while P4HB degraded gradually. P4HB scaffolds exhibited excellent tissue integration with dense connective tissue and a moderate initial host response. P4HB scaffolds induced a significantly higher M2/M1 ratio (1.70 ± 0.67 SD, score 0-4), as compared to PP mesh(0.99 ± 0.78 SD, score 0-4) at 180-days. CONCLUSIONS: P4HB scaffold facilitated a gradual load transfer to vaginal tissue over time. The fully absorbable P4HB scaffold, in comparison to PP mesh, has a favorable host response with comparable load-bearing capacity. If these results are also observed at longer follow-up in-vivo, a clinical study using P4HB for vaginal POP surgery may be warranted to demonstrate efficacy. TWEETABLE ABSTRACT: Degradable vaginal P4HB implant might be a solution for treatment of POP.

International Urogynecological Consultation (IUC): pathophysiology of pelvic organ prolapse (POP).

INTRODUCTION AND HYPOTHESIS: This manuscript is the International Urogynecology Consultation (IUC) on pelvic organ prolapse (POP) chapter one, committee three, on the Pathophysiology of Pelvic Organ Prolapse assessing genetics, pregnancy, labor and delivery, age and menopause and animal models. MATERIALS AND METHODS: An international group of urogynecologists and basic scientists performed comprehensive literature searches using pre-specified terms in selected biomedical databases to summarize the current knowledge on the pathophysiology of the development of POP, exploring specifically factors including (1) genetics, (2) pregnancy, labor and delivery, (3) age and menopause and (4) non-genetic animal models. This manuscript represents the summary of three systematic reviews with meta-analyses and one narrative review, to which a basic scientific comment on the current understanding of pathophysiologic mechanisms was added. RESULTS: The original searches revealed over 15,000 manuscripts and abstracts which were screened, resulting in 202 manuscripts that were ultimately used. In the area of genetics the DNA polymorphisms rs2228480 at the ESR1 gene, rs12589592 at the FBLN5 gene, rs1036819 at the PGR gene and rs1800215 at the COL1A1 gene are significantly associated to POP. In the area of pregnancy, labor and delivery, the analysis confirmed a strong etiologic link between vaginal birth and symptoms of POP, with the first vaginal delivery (OR: 2.65; 95% CI: 1.81-3.88) and forceps delivery (OR: 2.51; 95% CI: 1.24-3.83) being the main determinants. Regarding age and menopause, only age was identified as a risk factor (OR : 1.102; 95% CI: 1.02-1.19) but current data do not identify postmenopausal status as being statistically associated with POP. In several animal models, there are measurable effects of pregnancy, delivery and iatrogenic menopause on the structure/function of vaginal support components, though not on the development of POP. CONCLUSIONS: Genetics, vaginal birth and age all have a strong etiologic link to the development of POP, to which other factors may add or protect against the risk.

Animal models for pelvic organ prolapse: systematic review.

INTRODUCTION AND HYPOTHESIS: We aimed to summarize the knowledge on the pathogenesis of pelvic organ prolapse (POP) generated in animal models. METHODS: We searched MEDLINE, Embase, Cochrane and the Web of Science to establish what animal models are used in the study of suggested risk factors for the development of POP, including pregnancy, labor, delivery, parity, aging and menopause. Lack of methodologic uniformity precluded meta-analysis; hence, results are presented as a narrative review. RESULTS: A total of 7426 studies were identified, of which 51 were included in the analysis. Pregnancy has a measurable and consistent effect across species. In rats, simulated vaginal delivery induces structural changes in the pelvic floor, without complete recovery of the vaginal muscular layer and its microvasculature, though it does not induce POP. In sheep, first vaginal delivery has a measurable effect on vaginal compliance; measured effects of additional deliveries are inconsistent. Squirrel monkeys can develop POP. Denervation of their levator ani muscle facilitates this process in animals that delivered vaginally. The models used do not develop spontaneous menopause, so it is induced by ovariectomy. Effects of menopause depend on the age at ovariectomy and the interval to measurement. In several species menopause is associated with an increase in collagen content in the longer term. In rodents there were no measurable effects of age apart of elastin changes. We found no usable data for other species. CONCLUSION: In several species there are measurable effects of pregnancy, delivery and iatrogenic menopause. Squirrel monkeys can develop spontaneous prolapse.

Effects of non-ablative Er:YAG laser on the skin and the vaginal wall: systematic review of the clinical and experimental literature.

INTRODUCTION AND HYPOTHESIS: Er:YAG laser is frequently used in dermatology and gynecology. Clinical studies document high satisfaction rates; however, hard data on the effects at the structural and molecular levels are limited. The aim of this systematic review was to summarize current knowledge about the objective effects of non-ablative Er:YAG laser on the skin and vaginal wall. METHODS: We searched MEDLINE, Embase, Cochrane, and the Web of Science. Studies investigating objectively measured effects of non-ablative Er:YAG laser on the skin or vaginal wall were included. Studies of any design were included. Owing to the lack of methodological uniformity, no meta-analysis could be performed and therefore results are presented as a narrative review. RESULTS: We identified in vitro or ex vivo studies on human cells or tissues, studies in rats, and clinical studies. Most studies were on the skin (n = 11); the rest were on the vagina (n = 4). The quality of studies is limited and the settings of the laser were very diverse. Although the methods used were not comparable, there were demonstrable effects in all studies. Immediately after application the increase in superficial temperature, partial preservation of epithelium and subepithelial extracellular matrix coagulation were documented. Later, an increase in epithelial thickness, inflammatory response, fibroblast proliferation, an increase in the amount of collagen, and vascularization were described. CONCLUSIONS: Er:YAG laser energy may induce changes in the deeper skin or vaginal wall, without causing unwanted epithelial ablation. Laser energy initiates a process of cell activation, production of extracellular matrix, and tissue remodeling.

Use of a simple in vitro fatigue test to assess materials used in the surgical treatment of stress urinary incontinence and pelvic organ prolapse.

AIMS: Stress urinary incontinence and pelvic organ prolapse are very common conditions with a proportion of patients requiring implantation of synthetic materials for a durable repair. However increasing numbers of post-surgical complications have been reported related to the use of polypropylene meshes. One hypothesis for the adverse response is poor mechanical matching of the relatively stiff polypropylene mesh particularly as materials in the pelvic floor will need to cope with decades of distension as occurs with increase of intraabdominal pressure on coughing, laughing, or sneezing. METHODS: In this study we have undertaken a very simple fatigue testing regime to compare the mechanical abilities of six materials. Four commercial meshes in clinical use and two novel electrospun materials not yet evaluated in the clinic were assessed using a uniaxial tensile test. This was performed on six samples of each dry material and on another six samples of each material after just 3 days of fatigue conditions using a dynamic bioreactor. RESULTS: The four commercial materials showed permanent mechanical deformation after just 3 days of stretching these materials by 25% elongation on a regular dynamic cycle, whereas the two new materials presented more elastic properties without deformation. CONCLUSIONS: We suggest that a test as simple as this 3-day fatigue testing is sufficient to distinguish between materials which have already been found to cause complications clinically and newer materials yet to be tested clinically which will hopefully prove more mechanically appropriate for implantation in the pelvic floor.

First delivery and ovariectomy affect biomechanical and structural properties of the vagina in the ovine model.

INTRODUCTION AND HYPOTHESIS: Animal models are useful for investigating the genesis of pelvic floor dysfunction and for developing novel therapies for its treatment. There is a need for an alternative large-animal model to the nonhuman primate. Therefore we studied the effects of the first vaginal delivery, ovariectomy and systemic hormonal replacement therapy (HRT) on the biomechanical and structural properties of the ovine vagina. METHODS: We examined the gross anatomical properties of nulliparous, primiparous, ovariectomized multiparous, and ovariectomized hormone-replaced multiparous sheep (six animals per group). We also harvested mid-vaginal and distal vaginal tissue to determine smooth muscle contractility and passive biomechanical properties, for morphometric assessment of the vaginal wall layers, to determine collagen and elastin content, and for immunostaining for α-smooth muscle actin and estrogen receptor-α. RESULTS: There were no regional differences in the nulliparous vagina. One year after the first vaginal delivery, stiffness and contractility of the distal vagina were decreased, whereas the elastin content increased. The mid-vagina of ovariectomized sheep was stiff, and its epithelium was thin and lacked glycogen. HRT decreased the stiffness of the mid-vagina by 45% but had no measurable effect on contractility or elastin content, and increased epithelial thickness and glycogen content. HRT also increased the epithelial thickness and glycogen content of the distal vagina. At this location, there were no changes in morphology or stiffness. CONCLUSION: In sheep, life events including delivery and ovariectomy affect the biomechanical properties of the vagina in a region-specific way. Vaginal delivery mainly affects the distal region by decreasing stiffness and contractility. HRT can reverse the increase in stiffness of the mid-vagina observed after surgical induction of menopause. These observations are in line with scanty biomechanical measurements in comparable clinical specimens.

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.

Prenatally Acquired Multiple Limb Ischemia in a Very Low Birth Weight Monochorionic Twin.

Limb ischemia is an extremely rare event occuring in monochorionic twin pregnancy complicated by twin-to-twin transfusion syndrome (TTTS) and twin anemia polycythemia sequence (TAPS). The authors describe a case of TTTS and TAPS treated successfully using amnioreduction and laser ablation. However, severe ischemia of both lower extremities in the recipient twin developed after the fetal treatment. This serious complication was diagnosed on MRI in utero and confirmed postnatally. Elective amputation of the affected limbs was performed. The etiology of the disease remains unclear despite profound clinical and histopathological examinations; although the role of thromboembolism in monochorionic pregnancy seems to be most likely, this unique case of multiple limb ischemia with distinct macroscopic findings has not yet been described.

Circulating heat shock protein mRNA profile in gestational hypertension, pre-eclampsia & foetal growth restriction.

BACKGROUND & OBJECTIVES: Heat shock proteins (Hsp) are ubiquitously distributed phylogenetically conserved molecules that regulate cellular homeostasis and maintain the integrity and function of cellular proteins. Increased levels of Hsp in maternal circulation have been shown to be associated with increased risk of pregnancy related complications. The objective of this study was to explore extracellular Hsp mRNA levels in maternal circulation and quantified Hsp27, Hsp60, Hsp70, Hsp90 and Hsp70 binding protein 1 (HspBP1) mRNAs in maternal plasma samples using real-time reverse-transcriptase polymerase chain reaction. METHODS: Pregnancies with gestational hypertension (GH) (n = 33), pre-eclampsia (PE) with or without foetal growth restriction (FGR) (n = 78) and FGR (n = 25) were involved in the study. Hsp gene expression was analysed in relation to the severity of the disease with respect to the degree of clinical signs, requirements for the delivery and Doppler ultrasound parameters. RESULTS: Upregulation of Hsp70 was observed in patients with mild and severe PE (P = 0.004 and P = 0.005, respectively) and in pregnancies complicated with PE delivering before and after 34 wk of gestation regardless of the degree of clinical signs (P = 0.015 and P = 0.009, respectively). No difference in the expression of other Hsp genes among the studied groups was observed. No association between Hsp gene expression and Doppler ultrasonography parameters was found. INTERPRETATION & CONCLUSIONS: These data support that maternal circulation can reflect both maternal and foetal pathologic conditions. Hsp70 represents the sole plasmatic marker, and increased Hsp70 mRNA levels reflect maternal and placental stress response to pregnancy-related complications such as GH and PE, irrespective of the severity of the disease.

Assessment of placental and maternal stress responses in patients with pregnancy related complications via monitoring of heat shock protein mRNA levels.

The study describes the stress response in the central cotyledon zone of placental tissue and in maternal whole peripheral blood to pregnancy related complications including gestational hypertension (n = 31), preeclampsia w or w/o fetal growth restriction (n = 95), and fetal growth restriction (n = 39) using real-time RT-PCR and genes encoding Hsp27, Hsp60, Hsp70, Hsp90 and HspBP1 proteins. The placental tissue does not respond to pregnancy induced hypertension, fetal growth restriction and short-term severe preeclampsia that requires immediate termination of gestation. Upregulation of Hsp27, Hsp90 and HspBP1 appears just in case of long-term deteriorated conditions (usually in mild preeclampsia, that enable further continuation of gestation, when properly treated). On the other hand, maternal circulation is able to reflect both maternal and fetal pathologic conditions. While pregnancy related complications always induce upregulation of Hsp70 and downregulation of Hsp90 in maternal whole peripheral blood, the increase of Hsp60 mRNA levels occurs entirely in patients with preeclampsia and/or fetal growth restriction. Hsp60, Hsp70 and Hsp90 are dysregulated in maternal circulation irrespective of the severity of the disease (in both mild and severe preeclampsia) and the requirements for the delivery (before and after 34th week of gestation). Nevertheless, the highest Hsp60 mRNA levels may be observed in pregnancies with signs of the centralization of the fetal circulation associated with fetal hypoxia.

Circulating C19MC microRNAs in preeclampsia, gestational hypertension, and fetal growth restriction.

The objective of the study was to identify the profile of circulating C19MC microRNAs (miR-516-5p, miR-517*, miR-518b, miR-520a*, miR-520h, miR-525, and miR-526a) in patients with established preeclampsia (n = 63), fetal growth restriction (n = 27), and gestational hypertension (n = 23). We examined the correlation between plasmatic concentrations and expression levels of microRNAs and the severity of the disease with respect to clinical signs, requirements for the delivery, and Doppler ultrasound parameters. Using absolute and relative quantification approaches, increased extracellular C19MC microRNA levels (miR-516-5p, P = 0.037, P = 0.009; miR-517*, P = 0.033, P = 0.043; miR-520a*, P = 0.001, P = 0.009; miR-525, P = 0.026, P = 0.01; miR-526a, P = 0.03, P = 0.035) were detected in patients with preeclampsia. The association analysis pointed to no relationship between C19MC microRNA plasmatic concentrations and expression profile and identified risk factors for a poorer perinatal outcome. However, the dependence between the levels of plasmatic C19MC microRNAs and the pulsatility index in the middle cerebral artery and the values of cerebroplacental ratio was demonstrated. The study brought the interesting finding that the upregulation of miR-516-5p, miR-517*, miR-520a*, miR-525, and miR-526a is a characteristic phenomenon of established preeclampsia.

Retained products of conception - a retrospective analysis of 200 cases of surgical procedures for the diagnosis of residua postpartum.

OBJECTIVES: Postpartum retained products of conception are a relatively rare diagnosis occurring in approximately 1% of cases after spontaneous deliveries and abortions. The most common clinical signs are bleeding and abdominal pain. The diagnosis is based on clinical signs and ultrasound examination. MATERIAL AND METHODS: Retrospective analysis of 200 surgical procedures for the diagnosis of residua postpartum obtained in 64 months. We correlated the method and accuracy of diagnosis with definitive histological findings. RESULTS: During 64 months, we performed 23 412 deliveries. The frequency of procedures for diagnosis of retained products of conception (RPOC) was 0.85%. Most (73.5%) of the D&C were performed within six weeks of delivery. Histologically, the correct diagnosis was confirmed in 62% (chorion + amniotic envelope). There was interestingly lower concordance of histologically confirmed RPOC in post-CS patients (only 42%). In women after spontaneous delivery of the placenta, the diagnosis of RPOC was confirmed by histological correlate in 63%, and the highest concordance occurred in women after manual removal of the placenta in 75%. CONCLUSIONS: Concordance with histological findings of chorion or amnion was seen in 62% of cases; this means that the incidence rate in our study was around 0.53%. The lowest concordance is after CS deliveries, 42%. D&C for RPOC should be performed after adequate clinical evaluation and in the knowledge of 38% false positivity. There is certainly more space for a conservative approach under appropriate clinical conditions, especially in patients after CS.

The amenorrhea as a protective factor for healing of hysterotomy - a retrospective analysis one year postpartum.

OBJECTIVES: The good healing of the hysterotomy after cesarean section is important for subsequent pregnancies. However, the factors which improve this healing have not been completely described, yet. In this study, we focused on factors which may affect healing of hysterotomy within one year after delivery, such as menstruation, breastfeeding, and the use of the contraception. MATERIAL AND METHODS: Following delivery, total of 540 women were invited for three consecutive visits at six weeks, six months, and 12 months postpartum. The presence of menstruation, frequency of breastfeeding and contraception use were recorded. The scar was evaluated by vaginal ultrasound as already described. The impact of menstruation, breastfeeding, and contraception method on presence of niche was evaluated. RESULTS: The presence of menstruation increased odds to have niche by 45% (CI 1.046-2.018, p = 0.026). Secondarily, our results demonstrated a statistically significant protective effect of breastfeeding on the incidence of niche with OR 0.703 (CI 0.517-0.955, p = 0.024). Breastfeeding decreases odds to have niche by 30%. Also, the use of gestagen contraception lowered the odds by 40% and intrauterine device (IUD) or combine oral contraceptive (COC) by 46.5%. The other possibly intervening factors were statistically controlled. CONCLUSIONS: Amenorrhea, breast-feeding and progesterone-contraceptive decreases the risk of uterine niche within one year follow up.

In silico prediction of maximum perineal muscle strain during vaginal delivery by design of experiment.

BACKGROUND AND OBJECTIVE: The prevalence of pelvic floor muscle injuries induced by childbirth is higher than 23 % in the general women population. Such injuries can lead to prolapses and other pathologies in future female life. Leveraging computational biomechanics, the study implements an advanced female pelvic floor model for computing the maximum pelvic muscle strain, which serves as an injury risk indicator. The design of experiment method, abbreviated as DoE, is used to compute the maximum strain for boundary values of bony pelvis dimensions, namely the anterior-posterior diameter (abbreviated as APD) and the transverse diameter (abbreviated as TD). This is done in combination with small, medium and large percentiles of fetal head circumference (abbreviated as HC). METHODS: We utilized a previously developed finite element model of a female pelvic floor, as a reference, and enhanced it with new features, including a more detailed tissue geometry and advanced constitutive material models. The APD and TD dimensions were sourced from the set of MRI of 64 nulliparous women. This data was used to estimate the boundary dimensions of the female bony pelvis, combining both small and large values of APD and TD. Together with the 10th and the 95th percentiles for HC, a three-dimensional domain was constructed to assess the maximum pelvic muscle strain. In boundary cases, the maximum pelvic muscle strain was computed across 8 full-factorial design models (each situated at one corner of the domain, thereby combining the minimum and the maximum values of APD, TD and HC). This was done to define a response surface that predicts the maximum pelvic muscle strain within the domain. The accuracy of this response surface prediction was validated using 15 additional intermediate design models. These models were placed at the center of the domain (1 point), the centres of the domain boundary surfaces (6 points), and midway along each domain boundary edge (8 points). RESULTS: The maximum strain results for 8 combinations of APD, TD, and HC were employed to construct a linear response surface as a function of APD, TD, and HC. Tests at an additional 19 domain points served to evaluate the efficiency of the response surface prediction. The response surface demonstrated strong predictability, with an absolute average error of 1.52 %, an absolute median error of 1.52 %, and an absolute maximum error of 11.11 %. HC emerged as the most influencing dimension, accounting for 16 % of influence. CONCLUSIONS: The reference finite element pelvic floor model was scaled to 8 full-factorial female-specific pelvic floor models, which represent the combination of boundary values for APD, TD, and HC. The maximum pelvic floor muscle strain from these 8 models was used to design a response surface. When implementing the DoE approach to construct the response, there was consistent predictability for the maximum perineal muscle strain, as validated by the additional 19 intermediate design models. As a result, the response surface methodology can serve as an initial predictor for potential childbirth-induced pelvic floor muscle injury.

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.

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.