William R. Barone

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.

The Impact of Boundary Conditions on Surface Curvature of Polypropylene Mesh in Response to Uniaxial Loading

Exposure following pelvic organ prolapse repair has been observationally associated with wrinkling of the implanted mesh. The purpose of this study was to quantify the impact of variable boundary conditions on the out-of-plane deformations of mesh subjected to tensile loading. Using photogrammetry and surface curvature analyses, deformed geometries were accessed for two commercially available products. Relative to standard clamping methods, the amount of out-of-plane deformation significantly increased when point loads were introduced to simulate suture fixation in-vivo. These data support the hypothesis that regional increases in the concentration of mesh potentially enhance the host׳s foreign body response, leading to exposure.

THE EFFECT OF PREGNANCY AND POSTPARTUM RECOVERY ON THE VISCOELASTIC BEHAVIOR OF THE RAT CERVIX.

The objective of this study was to elucidate the normal functional adaptations of the cervix in pregnancy. Utilizing a Long-Evans rodent model, the cervix was divided into distal and proximal portions for virgin, mid-pregnant, and four weeks postpartum animals. The quasi-linear viscoelastic theory describes the elastic and viscous behavior of the cervix. A hydroxyproline assay was used to measure collagen content. The nonlinearity of the elastic response significantly increased throughout the entire cervix during pregnancy when compared to virgin samples (p < 0.05) and was similar to virgin samples postpartum. All viscous behavior, except for the short-term relaxation of the proximal cervix, significantly differed for pregnant specimens (p < 0.05) and remained similar to pregnant samples postpartum. Collagen content was found to increase by mid-pregnancy only in the proximal cervix when compared to virgin. Distal and proximal portions, however, were found to differ in collagen content at all time points (p < 0.05). This study finds that the cervix becomes elastically stiffer with increasing strain and exhibits increased viscous behavior during pregnancy, with incomplete recovery postpartum. These alterations allow for quick dissipation of loads, and are likely related to altered matrix organization and porosity reported by others.

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.

Viscoelastic Behavior of the Rat Uterine Cervix at Mid-Pregnancy

Preterm labor is the leading cause of neonatal mortality and accounts for 70% of the total cost of neonatal health care. Premature softening of the cervix has been identified as one of the primary causes of preterm labor. As the biochemistry of the cervix is distinct between the proximal and distal portions, the objective of this study was to determine the viscoelastic properties of these portions in mid-pregnancy (Day 15–16) relative to virgin Long-Evans rats. This will serve to establish baseline data for future studies that will aim to induce preterm labor in this model. The cervix was divided into distal and proximal portions that were tested independently. Each portion was tested in unconfined compression to 20% strain and held for 4 minutes followed by a recovery period of 30 minutes. The stress-relaxation response was modeled using the quasi-linear viscoelastic (QLV) theory developed by Professor Fung (1972). The parameters governing the viscous response, C, τ1 and τ2, were found to be significantly different between virgin and pregnant tissues in distal portions; however τ2 was the only viscous parameter found to be significantly different for the proximal portion (p<0.05). These results show an increased magnitude of the viscous response with more rapid relaxation for the pregnant cervix. Future studies will evaluate the cervix both postpartum and upon induction of preterm labor. Additionally, contractile and biochemical assays will be used to correlate these changes in passive behavior to active properties and tissue constituents.© 2010 ASME

Deformation of Transvaginal Mesh in Response to Multiaxial Loading

Synthetic mesh for pelvic organ prolapse (POP) repair is associated with high complication rates. While current devices incorporate large pores (>1 mm), recent studies have shown that uniaxial loading of mesh reduces pore size, raising the risk for complications. However, it is difficult to translate uniaxial results to transvaginal meshes, as in vivo loading is multidirectional. Thus, the aim of this study was to (1) experimentally characterize deformation of pore diameters in a transvaginal mesh in response to clinically relevant multidirectional loading and (2) develop a computational model to simulate mesh behavior in response to in vivo loading conditions. Tension (2.5 N) was applied to each of mesh arm to simulate surgical implantation. Two loading conditions were assessed where the angle of the applied tension was altered and image analysis was used to quantify changes in pore dimensions. A computational model was developed and used to simulate pore behavior in response to these same loading conditions and the results were compared to experimental findings. For both conditions, between 26.4% and 56.6% of all pores were found to have diameters <1 mm. Significant reductions in pore diameter were noted in the inferior arms and between the two superior arms. The computational model identified the same regions, though the model generally underestimated pore deformation. This study demonstrates that multiaxial loading applied clinically has the potential to locally reduce porosity in transvaginal mesh, increasing the risk for complications. Computational simulations show potential of predicting this behavior for more complex loading conditions.

AB289. SPR-16 A preliminary evaluation of vaginal alignment following a transvaginal procedure using MatriStem™ pelvic floor matrix in the rhesus macaque

Objective Implantation of biological or synthetic mesh is the most common method of surgical intervention for pelvic organ prolapse, however, complications ensuing from these surgical repairs occur in 15.5% of cases. MatristemTM (ACell, Inc., USA) Pelvic Floor Matrix is a urinary bladder matrix (UBM) device indicated for transvaginal repair. This device is remodeled and replaced by host tissue following implantation, which raises the concern that the process may result in a loss of support to the vagina. Thus, the goal of this study was to quantify measurable changes in vaginal alignment via magnetic resonance imaging (MRI) before (pre) and after (10 days and 3 months) a transvaginal procedure with this device in a rhesus macaque model. Methods Two rhesus macaques underwent a transvaginal procedure in accordance with the IACUC at the University of Pittsburgh (protocol #13081928). Level 1 & 2 support to the vagina was transected to simulate compromised support. Two sheets of 6-ply MatriStemTM were implanted to support the anterior and posterior vagina. Vaginal alignment was derived from MRIs taken pre, 10 days, and 3 months after surgery. The border of the vagina was manually traced, and used to calculate the centroid of each tracing. These centroids represent the path of the vagina through the pelvis. Further, a 3D coordinate system was mapped to the pelvis, and lines fit to the proximal and distal vagina were used to measure the angle of each line with respect to a cephalic oriented axis in the mid-sagittal plane, which is referred to as the angle of elevation. Results At 10 days, the angle of elevation became more acute by 8.6% and 17%, respectively. These changes reflect expectations of a tensioned transvaginal fixation of the vagina. At 3 months post-surgery, angles of elevation approached pre surgery conditions, indicating that MatriStemTM was providing a comparable level of support to native tissue, even following remodeling. Conclusions This preliminary study shows that MatriStem™ repair appears to be re-establishing vaginal support. Future work will aim to increase sample size and compare data to non-repaired controls and those repaired using synthetic mesh. Funding Source(s) ACell Inc. for funding these preliminary findings

Host Response to Biomaterials for Pelvic Floor Reconstruction

Biomaterial use in pelvic floor reconstruction has become an area of intense interest. The use of such products has dramatically increased in recent decades and synthetic biomaterials are considered the standard of care for surgical treatment of pelvic floor disorders such as stress urinary incontinence and pelvic organ prolapse. While some current urogyecological biomaterials achieve desirable efficacy, others have been met with controversy due to relatively high complication rates. In this chapter, we aim to provide the reader with a thorough understanding of the use of biomaterials in the pelvic floor. Specifically, this text will focus on the anatomy of the pelvic floor, highlighting the role of supportive structures of the female pelvis and the intended functions that biomaterials are expected to perform. In addition, we will detail previous successes and shortcomings in this field and discuss the challenges for biomaterials that must be considered in this anatomic location.

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