Exploring biomechanical methods to study the human vaginal wall.

AIMS: To critically review studies of the biomechanical properties of connective tissue in the normal and prolapsed human vaginal wall and to identify criteria that are suitable for in vivo measurements which could improve patient management. METHODS: This review covers past and current ex vivo and in vivo instrumentation and analytical methods related to the elastic and viscoelastic properties of vaginal wall connective tissues. RESULTS: Classical methods, including digital evaluation of the vagina, histological and biomechanical studies of fresh and frozen-thawed extracts, and biomechanical cadaveric tissue studies have important limitations and have yielded inconsistent results. Newer biomechanical methods may resolve these inconsistencies. One of the more promising is transient, vacuum-induced tissue expansion and relaxation, via cutometer-like devices. The technique permits noninvasive observation, applicable to longitudinal studies of patients. In vivo and ex vivo biomechanical methods may better match vaginal wall tissue properties to help with the design of surgical mesh materials, thus improving surgical support and healing. CONCLUSION: Methods have been identified to characterize the in vivo biomechanical behavior of the prolapsing vagina which may serve to advance the care of affected women. Neurourol. Urodynam. 36:499-506, 2017. © 2016 Wiley Periodicals, Inc.

Influence of body mass index on the biomechanical properties of the human prolapsed anterior vaginal wall.

INTRODUCTION AND HYPOTHESIS: We report the influence of body mass index (BMI) on the biomechanical properties of human prolapsed anterior vaginal wall (AVW) tissue samples. We hypothesize that women with AVW prolapse would have the same vaginal wall biomechanical properties regardless of their weight. METHODS: Following Institutional Review Board approval, age-comparable postmenopausal women with symptomatic stage II-III AVW prolapse underwent excision of a short vaginal wall sample during transvaginal prolapse repair. Excised samples were subjected to uniaxial tensile testing using an Instron 5655 (Instron, Norwood, MA, USA) within 2 h of harvest to measure intrinsic biomechanical properties. Patients were divided into two groups (A: BMI <25 and B: BMI >25) to compare tissue biomechanical properties after controlling for age and parity. RESULTS: From 2011 to 2013, 28 consecutive women were studied, 13 in group A and 15 in group B. Patients with BMI >25 developed higher tissue stresses, including higher tangent moduli, at selected strain levels than patients with BMI <25. CONCLUSIONS: Contrary to our hypothesis, this study observed a relationship between BMI and human AVW biomechanical properties, with more obese women having stiffer tissue properties.

Do biomechanical properties of anterior vaginal wall prolapse tissue predict outcome of surgical repair?

PURPOSE: We determined the relevance of the biomechanical properties of freshly harvested vaginal tissue during large cystocele repair on clinical outcome at a minimum 1-year followup. MATERIALS AND METHODS: With institutional review board approval we prospectively studied the biomechanical properties of full thickness vaginal wall tissue from postmenopausal women with symptomatic Baden-Walker prolapse undergoing anterior vaginal wall suspension with cystocele repair from 2002 to 2005. A standardized biomechanical protocol was applied with stress-strain curves for Young's modulus obtained by blinded investigators. Failed repair was defined as recurrence on examination or reoperation for recurrent anterior prolapse. RESULTS: A total of 32 patients (median age 72 years) had a median followup of 34 months (range 12 to 62). Median Young's modulus was statistically different in tissue samples transported in immersed vs moistened media (median 3.8 vs 7.6, p = 0.008). Associations between Young's modulus and clinical variables were described. On followup 7 patients experienced failure of the repair. After controlling for tissue transport protocol no association was seen between Young's modulus and failures (HR 1.1, p = 0.34). CONCLUSIONS: This study found no association between Young's modulus and clinical results at long-term followup. This finding suggests that retropubic scarring and pelvic floor muscle properties may be more important for a successful reparative outcome than the intrinsic properties of the vaginal wall.

Methodology for biomechanical testing of fresh anterior wall vaginal samples from postmenopausal women undergoing cystocele repair.

GOAL: To explore the methodological challenges of biomechanical testing of freshly harvested human anterior vaginal wall (HAVW) samples. METHOD: Longitudinal full-thickness samples of HAVW were excised during cystocele repair in postmenopausal women and age-matched controls. Two methods of tissue storage during transport were compared. All samples were prepared for uniaxial testing within 2 hr of harvest and loaded at a rate of 0.5 mm/sec, until irreversible deformation was observed. Young's modulus and other parameters were extracted from the tensile stress-strain curves. RESULTS: Samples were obtained over 2 years from 42 patients. Significant differences in biomechanical parameters were noted based on the degree of hydration of the tissue, suggesting that the wetter samples were mechanically weaker. CONCLUSIONS: This study reports on a new method for testing the biomechanical properties of freshly harvested HAVW tissues and the impact of tissue hydration during transport between the operating room and the testing lab.

Formulation and characterization of a covalently coated magnetic nanogel.

The aim of this study was to develop a novel method to encapsulate magnetic nanoparticles (MNPs) with polymer via covalent bonding, in order to increase the magnetic nanoparticle stability and ease the synthesis process. In this technique, silane coated MNPs act as a template for polymerization of the monomer N-isopropylacrylamide, (NIPA) via radical polymerization. Transmission and scanning electron microscopy indicated the size of the original MNP was approximately 10 nm, the silane-coated MNP was 40 nm and the NIPA silane-coated MNP was 100 +/- 10 nm. Chemical composition and chemical state analysis of NIPA MNPs by FTIR and XPS showed that the MNPs were actually encapsulated by silane and NIPA. Furthermore, the magnetic properties of different layers on the MNP, analyzed by SQUID, indicated a decrease in saturation magnetization for each layer. The results demonstrate the feasibility of encapsulation of the MNP with NIPA by means of silane covalent bonding. Future work will investigate the phase transition and biocompatibility properties of the NIPA-coated MNP for drug delivery and tissue engineering applications.

Monocyte activation in on-pump versus off-pump coronary artery bypass surgery.

OBJECTIVE: Monocyte activation plays a key role in amplifying both inflammatory and coagulopathic sequelae in patients undergoing on-pump coronary artery bypass graft (CABG) surgery. Off-pump CABG diminishes, but does not eliminate, the systemic inflammatory response and its influence on monocyte activation remains unclear. This study was performed to determine if off-pump CABG suppresses all features of monocyte activation. DESIGN: Prospective, controlled, clinical study. SETTING: University-affiliated veterans affairs hospital and laboratory. PARTICIPANTS: Twenty-two patients scheduled to undergo primary CABG surgery (11 on-pump and 11 off-pump). INTERVENTIONS: On-pump and off-pump CABG surgery was performed via median sternotomy. Anticoagulation and heparin reversal were identical. Moderate hypothermia (28 degrees-30 degrees C) was used for on-pump CABG surgery, whereas temperature was maintained above 35.5 degrees C for off-pump CABG. No antifibrinolytic agents were used. MEASUREMENTS AND MAIN RESULTS: Perioperative monocyte changes were assessed by using cellular (CD11b, monocyte-platelet conjugates) and secreted markers (plasma IL-6, IL-8, and IL-10) measured at 6 time points before, during, and after CABG surgery. Off-pump CABG surgery completely blocked the increases in monocyte CD11b expression (p < 0.001) and monocyte-platelet conjugate formation (p < 0.001) observed in the on-pump group. In contrast, plasma interleukin levels were significantly elevated in both groups, although off-pump CABG surgery resulted in lower levels (p < 0.001) and a delayed time course. CONCLUSIONS: Off-pump CABG surgery attenuates monocyte secreted cytokines and completely suppresses activation-dependent monocyte cell-surface changes (CD11b, monocyte-platelet conjugate formation). Whether these pathophysiologic differences in monocyte activation translate into a reduction in adverse events after CABG surgery warrants a larger, randomized, outcomes study.

Phagocyte responses to degradable polymers.

Although many biodegradable polymers, such as poly-L-lactic acid and poly-L-glycolic acid, are preferentially composed of biological residues normally present in the human body, implants made of these materials often trigger inflammatory and fibrotic responses. Unfortunately, the mechanisms involved in degradable material-mediated tissue responses remain largely unknown. Using animal implantation and cell culture system models, we found a strong correlation between the rate of material degradation and the degree of inflammatory response to material implants. Furthermore, we have identified that both water-soluble and water-insoluble degradation products are potent triggers of phagocyte activation, including at the least, superoxide production. These results support a new concept that slow degradation may improve the biocompatibility of degradable drug-releasing particles and tissue engineering scaffolds.

Selective tessellation algorithm for modeling interactions between surgical instruments and tissues.

We present a selective spatial tessellation algorithm that is specifically optimized for instrument-to-tissue and instrument-to-instrument collision detection cases, which are the essential part of interaction modeling in surgery simulation with haptic feedback. Virtual surgeries demand haptic rate collision solutions only when instruments are involved in collisions. Other collision cases can be processed at slower rates. The proposed selective tessellation algorithm is capable of differentiating among various collision cases and assigning different priorities to their processing. Without making assumptions about any object movement, the algorithm derives clipping volume as collision detection regions which tightly enclose the objects of interest. Results of implementation of the algorithm in a surgical simulation are provided.

Current status of direct pulp-capping materials for permanent teeth.

Direct pulp-capping is a method for treating exposed vital pulp with dental material to facilitate the formation of reparative dentin and to maintain vital pulp. Two types of pulp-capping materials, calcium hydroxide and mineral trioxide aggregate, have been most commonly used in clinics, and an adhesive resin has been considered a promising capping material. However, until now, there has been no comprehensive review of these materials. Therefore, in this paper, the composition, working mechanisms and clinical outcome of these types of pulp-capping materials are reviewed.

Mechanical Interaction of an Expanding Coiled Stent with a Plaque-Containing Arterial Wall: A Finite Element Analysis.

Wall injury is observed during stent expansion within atherosclerotic arteries, related in part to stimulation of the inflammatory process. Wall stress and strain induced by stent expansion can be closely examined by finite element analysis (FEA), thus shedding light on procedure-induced sources of inflammation. The purpose of this work was to use FEA to examine the interaction of a coiled polymer stent with a plaque-containing arterial wall during stent expansion. An asymmetric fibrotic plaque-containing arterial wall model was created from intravascular ultrasound (IVUS) images of a diseased artery. A 3D model for a coil stent at unexpanded state was generated in SolidWorks. They were imported into ANSYS for FEA of combined stent expansion and fibrotic plaque-distortion. We simulated the stent expansion in the plaqued lumen by increasing balloon pressure from 0 to 12 atm in 1 atm step. At increasing pressure, we examined how the expanding stent exerts forces on the fibrotic plaque and vascular wall components, and how the latter collectively resist and balance the expansive forces from the stent. Results show the expanding coiled stent creates high stresses within the plaque and the surrounding fibrotic capsule. Lower stresses were observed in adjacent medial and adventitial layers. High principal strains were observed in plaque and fibrotic capsule. The results suggest fibrotic capsule rupture might occur at localized regions. The FEA/IVUS method can be adapted for routine examination of the effects of the expansion of selected furled stents against IVUS-reconstructed diseased vessels, to improve stent deployment practices.

Permeable guidance channels containing microfilament scaffolds enhance axon growth and maturation.

Successful peripheral nerve regeneration is still limited in artificial conduits, especially for long lesion gaps. In this study, porous poly(L-lactide-co-DL-lactide, 75:25) (PLA) conduits were manufactured with 16 poly(L-lactide) (PLLA) microfilaments aligned inside the lumen. Fourteen and 18 mm lesion gaps were created in a rat sciatic nerve lesion model. To evaluate the combined effect of permeable PLA conduits and microfilament bundles on axon growth, four types of implants were tested for each lesion gap: PLA conduits with 16 filaments; PLA conduits without filaments; silicone conduits with 16 filaments; and silicone conduits without filaments. Ten weeks following implantation, regeneration within the distal nerve was compared between corresponding groups. Antibodies against the markers S100, calcitonin gene related peptide (CGRP), RMDO95, and P0 were used to identify Schwann cells, unmyelinated axons, myelinated axons, and myelin, respectively. Results demonstrated that the filament scaffold enhanced tissue cable formation and Schwann cell migration in all groups. The filament scaffold enhanced axonal regeneration toward the distal stump, especially across long lesion gaps, but significance was only achieved with PLA conduits. When compared to corresponding silicone conduits, permeable PLA conduits enhanced myelinated axon regeneration across both lesion gaps and achieved significance only in combination with filament scaffolds. Myelin staining indicated PLA conduits supported axon myelination with better myelin quantity and quality when compared to silicone conduits.

Mechanical properties and in vitro degradation of bioresorbable fibers and expandable fiber-based stents.

Bioresorbable polymeric support devices (stents) are being developed in order to improve the biocompatibility and drug reservoir capacity of metal stents, as well as to offer a temporary alternative to permanent metallic stents. These temporary devices may be utilized for coronary, urethral, tracheal, and other applications. The present study focuses on the mechanical properties of bioresorbable fibers as well as stents developed from these fibers. Fibers made of poly(L-lactide) (PLLA), polydioxanone (PDS), and poly(glycolide-co-epsilon-caprolactone) (PGACL) were studied in vitro. These fibers combine a relatively high initial strength and modulus together with sufficient ductility and flexibility, and were therefore chosen for use in stents. The effect of degradation on the tensile mechanical properties and morphology of these fibers was examined. The expandable stents developed from these fibers demonstrated excellent initial radial compression strength. The PLLA stents exhibited excellent in vitro degradation resistance and can therefore support body conduits such as blood vessels for prolonged periods of time. PDS and PGACL stents can afford good support for 5 and 2 weeks, respectively, and can therefore be utilized for short-term applications. The degradation resistance of the stents correlates with the profile of mechanical property deterioration of the corresponding bioresorbable fibers.

Haptic herniorrhaphy simulation with robust and fast collision detection algorithm.

Collision detection and soft tissue deformation are two major research challenges in real time VR based simulation, especially when haptic feedback is required. We have developed a real time collision detection algorithm for a prototype laparoscopic surgery trainer. However, this algorithm makes no assumptions about its applications and thus can be a generic solution to complicated collision detection problems. For soft tissue modeling, we use the mass-spring model enhanced with volume constraint and, stability control methods. We use both the new collision detection and tissue modeling algorithms in a bimanual hernia repair simulator which performs a mesh prosthesis stapling operation in real time.

Molecular responses of vascular smooth muscle cells and phagocytes to curcumin-eluting bioresorbable stent materials.

A major complication of coronary stenting is restenosis, often accompanied by inflammatory reactions and smooth muscle cell proliferation. Curcumin has been shown to possess anti-inflammatory and anti-proliferative properties, thus we hypothesize that locally released curcumin by coronary stent would diminish in-stent restenosis. As a first test of this hypothesis, curcumin-eluting PLLA films (C-PLLA) were produced and the anti-inflammatory and anti-proliferative properties were then tested using peritoneal phagocytes and human coronary artery smooth muscle cell (hCASMCs) culture systems. We find that the addition of curcumin reduced phagocyte accumulation and activation on C-PLLA films. On the other hand, C-PLLA significantly reduced the proliferation, but not the adhesion, of hCASMCs. The molecular responses of hCASMCs to C-PLLA were further assessed by cDNA microarray analysis. Curcumin up-regulated genes related to apoptosis and enhanced the expression of anti-proliferative and anti-inflammatory factors, and of antioxidants. Equally important, C-PLLA inhibited the cell cycle progression of adherent hCASMCs. The results suggest that curcumin regulates gene expression and cell function through the protein kinase (PK) and mitogen-activated protein kinase (MAPK) pathways. These results support the use of curcumin to inhibit in-stent restenosis.

Synergistic improvements in cell and axonal migration across sciatic nerve lesion gaps using bioresorbable filaments and heregulin-beta1.

The success of entubulation for peripheral nerve regeneration is still limited, especially with long lesion gaps. In this study, we examined if regeneration could be enhanced by constructing implants to both align axonal growth and promote Schwann cell proliferation and migration. Silicone implants were used to bridge a 1.4-cm gap in the rat sciatic nerve. Adult female Sprague-Dawley rats were divided into four groups of tubes containing either 1) Matrigel; 2) Matrigel and heregulin; 3) Matrigel and poly(L-lactic acid) (PLLA) microfilaments; or 4) Matrigel, PLLA microfilaments, and heregulin. Ten weeks postimplantation, the number of axons and Schwann cells were measured at the distal end of implants. Implants with microfilaments displayed better tissue cable formation, increased Schwann cell migration, and regeneration of anti-calcitonin gene-related peptide-positive axons, but not RMDO95-positive axons compared with nonfilament-containing groups. Heregulin treatment caused an increase in Schwann cell number, but it demonstrated no significant improvement in either tissue cable formation or axon number. Extensive regeneration was observed through implants containing Matrigel, microfilaments, and heregulin, which induced significant improvements in the number and longitudinal organization of both Schwann cells and axons. These results indicate that physical guidance of microfilaments and the Schwann cell growth factor, heregulin, act synergistically to improve nerve regeneration across long lesion gaps.

Molecular responses of vascular smooth muscle cells to paclitaxel-eluting bioresorbable stent materials.

We studied the influence of paclitaxel, eluted from poly(L-lactic acid) (PLLA), on cultured vascular smooth muscle cell (VSMC) proliferation as a model of bioresorbable stent-induced restenosis. We blended paclitaxel in cast PLLA films (P-PLLA), demonstrating controlled release of the drug, then studied VSMC adhesion, proliferation, and gene expression profiles. No difference in cell adhesion was found between P-PLLA and PLLA controls (105 +/- 12% of PLLA controls). However, P-PLLA significantly reduced VSMC proliferation (40 +/- 15% of PLLA controls, p < 0.05). Using cDNA microarray technology, we identified major effects of P-PLLA, including: upregulation of genes related to apoptosis, anti-proliferation and antioxidation; and suppression of cell cycle regulators and cell survival markers. The expression patterns indicate that P-PLLA regulates gene expression and cell functions via new pathways, including receptor tyrosine kinase (RTKs), mitogen-activated protein kinase (MAPKs), and protein kinase (PKs, e.g., PKA) pathways, in addition to the stabilization of polymerized-microtubules.

Protein-loaded bioresorbable fibers and expandable stents: Mechanical properties and protein release.

There is an increasing interest in bioresorbable polymeric stents for coronary, urethral and tracheal applications. These stents can support body conduits during their healing process and release biologically active agents from an internal reservoir to the surrounding tissue. A removal operation is not needed. Bioresorbable poly(L-lactic acid) fibers were prepared through melt spinning accompanied by a postpreparation drawing process. Novel expandable bioresorbable stents were developed from these fibers. Bioresorbable microspheres containing albumin were prepared and attached to the stents, to serve as a protein reservoir coating. The controlled release of albumin from the microsphere-loaded stent was studied. The fibers combine high strength and modulus, together with good ductility and flexibility. An increase in draw ratio increases the tensile strength and modulus and decreases the ultimate strain. The stents demonstrated excellent initial radial compression strength and good in vitro degradation resistivity, which makes them applicable for supporting blood vessels for at least 20 weeks. Microspheres bound to these stents enable effective protein loading, without reducing the stent's mechanical properties. The protein release from the microsphere-loaded stent occurs by diffusion, is determined mainly by the initial molecular weight of the bioresorbable polymer and its erosion rate, and is strongly affected by the microsphere structure.

Simulation of bleeding during laparoscopic herniorrhaphy.

Simulation of intragastric bleeding due to an accidental cut by the surgeon is an important component of a virtual laparoscopic herniorrhaphy trainer. We present a method for simulating bleeding during laparoscopic hemiorrhaphy here. The various approaches used in previous research work are reviewed and our present approach is justified. Physically based fluid models used in computer graphics are used to simulate bleeding.

Adaptive hybrid interpolation techniques for direct Haptic rendering of isosurfaces.

Direct Haptic rendering of voxels from an anatomical dataset provides patient specific haptic feedback vital for diagnosis and surgical planning. Our algorithm uses zero sets of scalar trivariate function for polynomial interpolation with sixty-four neighborhood points to generate isosurfaces on the fly for haptic rendering. This approach gives continuity in surfaces as well as better capture of isosurface features of the medical dataset. The detailed algorithm is presented along with the description of results from haptically rendering medical datasets.

Viscoelastic properties measurement of the prolapsed anterior vaginal wall: a patient-directed methodology.

OBJECTIVE: In-vivo measurement of the viscoelastic properties of the prolapsed anterior vaginal wall (AVW) in post-menopausal women undergoing cystocele repair. STUDY DESIGN: A BTC-2000 cutometer-like instrument was introduced during vaginal repair of symptomatic stage 2-3 AVW prolapse. Under anesthesia, 10-mm orifice probe was applied to the AVW at the level of the bladder neck. A suction pressure ramp (0 to -147 mmHg in 6s) was delivered causing tissue uplift, followed by immediate release to 0 mmHg, measuring tissue relaxation for 20s. Similar measurements were performed over the suprapubic region (SP) for comparison purpose. The rate of tissue recovery was obtained by fitting a Voigt model to the data and expressing results as the ratio E/η [(spring modulus E)/(dashpot viscosity η)]. The effective strain energy (SE) was calculated from the pressure-uplift data and evaluated from initiation to: (1) maximum storage in tissue at peak vacuum; (2) tissue recovery after vacuum release; (3) net SE loss over the entire loading-unloading cycle. RESULTS: In 22 women, higher AVW peak and residual tissue uplift values, and lower E/η ratios were found compared with SP results. The AVW stored less elastic strain energy at peak vacuum than did the SP, and AVW net energy loss over the uplift-recovery cycle was greater than for SP controls. Not only was the AVW more compliant than the SP, with higher viscous damping, but the tissue was also less able to store recoverable energy upon distension. CONCLUSION: Such in-vivo measurements quantify the biomechanical properties of the prolapsed AVW and may assist in its management.