Stacy Palcsey

Vaginal degeneration following implantation of synthetic mesh with increased stiffness

To compare the impact of the prototype prolapse mesh Gynemesh PS with that of two new‐generation lower stiffness meshes, UltraPro and SmartMesh, on vaginal morphology and structural composition.

Deterioration in biomechanical properties of the vagina following implantation of a high-stiffness prolapse mesh

To define the impact of prolapse mesh on the biomechanical properties of the vagina by comparing the prototype Gynemesh PS (Ethicon) to two new‐generation lower stiffness meshes, SmartMesh (Coloplast) and UltraPro (Ethicon).

The impact of prolapse mesh on vaginal smooth muscle structure and function

To evaluate the impact of prolapse meshes on vaginal smooth muscle structure (VaSM) and function, and to evaluate these outcomes in the context of the mechanical and textile properties of the mesh.

Impact of parity on ewe vaginal mechanical properties relative to the nonhuman primate and rodent.

Introduction and hypothesisParity is the leading risk factor for the development of pelvic organ prolapse. To assess the impact of pregnancy and delivery on vaginal tissue, researchers commonly use nonhuman primate (NHP) and rodent models. The purpose of this study was to evaluate the ewe as an alternative model by investigating the impact of parity on the ewe vaginal mechanical properties and collagen structure.MethodsMechanical properties of 15 nulliparous and parous ewe vaginas were determined via uniaxial tensile tests. Collagen content was determined by hydroxyproline assay and collagen fiber thickness was analyzed using picrosirius red staining. Outcome measures were compared using Independent samples t or Mann–Whitney U tests. ANOVA (Gabriel’s pairwise post-hoc test) or the Welch Alternative for the F-ratio (Games Howell post-hoc test) was used to compare data with previously published NHP and rodent data.ResultsVaginal tissue from the nulliparous ewe had a higher tangent modulus and tensile strength compared with the parous ewe (p < 0.025). The parous ewe vagina elongated 42 % more than the nulliparous ewe vagina (p = 0.015). No significant differences were observed in collagen structure among ewe vaginas. The tangent modulus of the nulliparous ewe vagina was not different from that of the NHP or rodent (p = 0.290). Additionally, the tangent moduli of the parous ewe and NHP vaginas did not differ (p = 0.773).ConclusionsParity has a negative impact on the mechanical properties of the ewe vagina, as also observed in the NHP. The ewe may serve as an alternative model for studying parity and ultimately prolapse development.

Towards rebuilding vaginal support utilizing an extracellular matrix bioscaffold

As an alternative to polypropylene mesh, we explored an extracellular matrix (ECM) bioscaffold derived from urinary bladder matrix (MatriStem™) in the repair of vaginal prolapse. We aimed to restore disrupted vaginal support simulating application via transvaginal and transabdominal approaches in a macaque model focusing on the impact on vaginal structure, function, and the host immune response. In 16 macaques, after laparotomy, the uterosacral ligaments and paravaginal attachments to pelvic side wall were completely transected (IACUC# 13081928). 6-ply MatriStem was cut into posterior and anterior templates with a portion covering the vagina and arms simulating uterosacral ligaments and paravaginal attachments, respectively. After surgically exposing the correct anatomical sites, in 8 animals, a vaginal incision was made on the anterior and posterior vagina and the respective scaffolds were passed into the vagina via these incisions (transvaginal insertion) prior to placement. The remaining 8 animals underwent the same surgery without vaginal incisions (transabdominal insertion). Three months post implantation, firm tissue bands extending from vagina to pelvic side wall appeared in both MatriStem groups. Experimental endpoints examining impact of MatriStem on the vagina demonstrated that vaginal biochemical and biomechanical parameters, smooth muscle thickness and contractility, and immune responses were similar in the MatriStem no incision group and sham-operated controls. In the MatriStem incision group, a 41% decrease in vaginal stiffness (P=0.042), a 22% decrease in collagen content (P=0.008) and a 25% increase in collagen subtypes III/I was observed vs. Sham. Active MMP2 was increased in both Matristem groups vs. Sham (both P=0.002). This study presents a novel application of ECM bioscaffolds as a first step towards the rebuilding of vaginal support. STATEMENT OF SIGNIFICANCE Pelvic organ prolapse is a common condition related to failure of the supportive soft tissues of the vagina; particularly at the apex and mid-vagina. Few studies have investigated methods to regenerate these failed structures. The overall goal of the study was to determine the feasibility of utilizing a regenerative bioscaffold in prolapse applications to restore apical (level I) and lateral (level II) support to the vagina without negatively impacting vaginal structure and function. The significance of our findings is two fold: 1. Implantation of properly constructed extracellular matrix grafts promoted rebuilding of level I and level II support to the vagina and did not negatively impact the overall functional, morphological and biochemical properties of the vagina. 2. The presence of vaginal incisions in the transvaginal insertion of bioscaffolds may compromise vaginal structural integrity in the short term.

Pregnancy and parturition negatively impact vaginal angle and alter expression of vaginal MMP-9

Background Parity is the greatest risk factor for the development of pelvic organ prolapse. The normally supported vagina is pulled up and back over the levator ani. Loss of vaginal angulation has been associated with prolapse and may represent injury to the vaginal supportive tissues. Objective We proposed and examined the following hypotheses: (1) pregnancy and delivery impact vaginal support, leading to loss of vaginal angle; (2) vaginal angulation is restored postpartum; and (3) uncomplicated vaginal delivery (VD) is associated with accelerated remodeling of the vaginal fibrillar matrix. Materials and Methods We prospectively enrolled a cohort of nulliparas in the first trimester of pregnancy, and abstracted demographic and delivery data. Metalloproteinase 9 (MMP‐9) activity in the vagina was determined in the first and third trimesters and 1 year postpartum using a substrate activity assay. Uncomplicated VD was defined as none of the following: cesarean delivery, forceps or vacuum use, shoulder dystocia, obstetric anal sphincter laceration, or prolonged second‐stage labor. Women were grouped dichotomously for comparison based on this definition. A subset of participants underwent transperineal ultrasound. Results We enrolled 173 women with mean age of 25 ± 6 years and a body mass index of 20 ± 7 kg/m2. Of the women, 67% identified as white/Caucasian, 27% black/African American, or 6% Hispanic/Latina. The mean delivery age was 39 ± 3 weeks, with 59% of participants experiencing uncomplicated VD. The MMP‐9 median activity (ng/mg protein) was 242.0 (IQR, 18.7, 896.8; n = 157) in the first trimester, 130.8 (IQR, 14.6, 883.8; n = 148) in the third trimester, and 463.5 (IQR, 92.2, 900.0; n = 94) postpartum. The MMP‐9 activity increased between the third trimester and 1 year postpartum (P = .006), with no significant difference between MMP‐9 values in the first and third trimesters (P = .674). The vaginal angle became less acute from the first to the third trimester, and this change persisted postpartum. The vaginal angulation over the levator plate became more acute between the third trimester and postpartum in women who experienced uncomplicated VD compared to those who did not (−6.4 ± 22.1 degrees vs 17.5 ± 14.8 degrees; P = .017). Higher MMP‐9 activity postpartum was associated with uncomplicated VD, with 67% of women in the third tertile achieving uncomplicated VD versus 39% in the first tertile (P = .029). Conclusion Loss of vaginal angulation occurs between trimesters, and women do not recover their baseline resting angle postpartum. MMP‐9 activity increases postpartum. Women experiencing uncomplicated VD demonstrate higher postpartum MMP‐9 activity and are more likely to have recovered their vaginal angle.

The Impact of Mesh Implantation on Vaginal Smooth Muscle Innervation and Contraction

Pelvic organ prolapse (POP) is a multifactorial disorder characterized by the descent of the pelvic organs into the vaginal canal. This disorder is associated with decreased quality of life, and even depression, yet 50% of women over the age of fifty are living with POP. The cost associated with the repair of POP exceeds one billion dollars annually, in the United States alone. This rather exorbitant figure includes the cost of surgery performed for symptom management, but does not include strategies which address the underlying cause of the disorder for which there are none. Because failure rates of native tissue repairs are as high as 30%, vaginal mesh is increasingly used in the surgical repair of POP. The procedure aims to reinforce the fibromuscular layer of the vagina and the paravaginal attachments, thus providing structural integrity to the weakened native tissues. However, the use of mesh is limited by mesh-related complications including exposure, erosion, pain contraction and infection.Copyright

Parity Negatively Impacts the Uniaxial Mechanical Properties of the Vagina in the Ewe

Pelvic organ prolapse (POP) is a common disorder with a profoundly negative impact on the physical and psychological health of women worldwide; however, the exact etiology is currently unknown. Parity, defined as the number of births, is commonly identified as one of the leading risk factors for the development of POP. The objective of this study was to examine the impact of parity on the uniaxial mechanical properties of the sheep vagina along the longitudinal direction. The findings of this study revealed that parity negatively impacts the tangent modulus (54% decrease), tensile strength (54% decrease), and strain-energy density (47% decrease) of the vagina in the ewe (female sheep). Based on similar findings in primate, these data suggest that the ewe may serve as a cheaper alternative for studying the pathogenesis of POP moving forward.Copyright