Novel patch biomaterial treatment for colon diverticulosis in swine model.

Current leading managements for diverticular disease cannot prevent the recurrence of diverticulitis, bleeding and/or other complications. There is an immediate need for developing new minimal invasive therapeutic strategies to prevent and treat this disease. Through a biomechanical analysis of porcine colon with diverticular lesions, we proposed a novel adhesive patch concept aiming at mechanical reconstruction of the diseased colon wall. This study aims to evaluate the surgical feasibility (safety and efficacy) of pulmonary visceral pleura (PVP) patch therapy using a pig model of diverticulosis. Six female Yucatan miniature pigs underwent collagenase injection (CI) for the development of diverticular lesions. The lesions in each animal either received patch implantation (treated group, n = 40 for 6 pigs) or left intact (untreated group, n = 44 for 6 pigs). The normal colonic wall in each animal received patch implantation at two spots to serve as control (n = 12 for 6 pigs). After 3 months of observation, the performance and safety of the patch treatment were evaluated through macroscopic and histological examination. We found that 95% of pouch-like herniation of the mucosa was prevented from the colon wall with the treatment. The pouch diameter was significantly reduced in the treated group as compared to the untreated group (p < 0.001). The patch application caused a significant increase in the levels of collagen of the colon tissue as compared to the untreated and control groups (p < 0.001). No difference was found in the lymphocyte and macrophage inflammatory infiltrate between the groups. Our results suggest that patch treatment efficiently inhibits the diverticular pouch deformation and promotes the healing of the colon wall with a normal inflammatory response, which may minimize the risk of diverticulosis reoccurrence and complications over time.

Search for an Optimal Design of a Bioprosthetic Venous Valve: In silico and in vitro Studies.

OBJECTIVE/BACKGROUND: Valve incompetence is a progressive disease of the venous system that may eventually lead to venous hypertension, pain, and ulcers. There is a need for a venous valve prosthesis to replace incompetent valves. Computational and experimental investigations on venous valve design and associated haemodynamics will undoubtedly advance prosthesis design and treatments. Here, the objective is to investigate the effect of venous valve on the fluid and solid mechanics. The hypothesis is that there exists a valve geometry that maximises leaflet shear stress (LSS) but minimises leaflet intramural stress (LIS; i.e., minimise stress ratio = LIS/LSS). METHODS: To address the hypothesis, fully dynamic fluid-structure interaction (FSI) models were developed. The entire cycle of valve opening and closure was simulated. The flow validation experiments were conducted using a stented venous valve prosthesis and a pulse duplicator flow loop. RESULTS: Agreement between the output of FSI simulations and output of pulse duplicator was confirmed. The maximum flow rates were within 6% difference, and the total flow during the cycle was within 10% difference. The simulated high stress ratio region at the leaflet base (five times the leaflet average) predicted the disease location of the vast majority of explanted venous valves reported in clinical literature. The study found that the reduced valve height and leaflet dome shape resulted in optimal performance to provide the lowest stress ratio. CONCLUSION: This study proposes an effective design of venous prostheses and elaborates on the correlations of venous valve with clinical observations.

Hemodynamics of venous valve pairing and implications on helical flow.

BACKGROUND: It has been shown that venous valves have pairing arrangements with specific relative orientation and spacing that contribute to helical flows. The studies to date have not quantified the hemodynamic impact of helical flow formation. A computational model allows various valve orientations and spacings to be studied to better understand the hemodynamic effect of valve pairing. METHODS: Simulations were performed for paired valves at physiologically relevant spacing and orientations to study the flow features and hemodynamics associated with valve pairing configurations. The wall shear stress (WSS), residence time, and pressure drop were evaluated for the various valve pairing cases. RESULTS: It was found that the WSS on the lumen flow side (front) of the leaflet is several times higher than on the valve pocket side (back). With orthogonal paired valves, the WSS at the critical back side is increased. Helical flow was clearly observed only with orthogonal valve pairing. The residence time was reduced to less than half (0.47 vs 1.16 seconds) in the orthogonal valve case compared with the parallel valve cases. The farther spaced valves (6 cm) had the highest residence time. CONCLUSIONS: This simulation study shows that helical flow in the veins of lower extremities is strongly dependent on the relative orientation and spacing of the valves. For optimal orientation (∼90 degrees) and spacing (∼4 cm), strong helical flow is seen, which enhances WSS and reduces the flow resistance and residence time. These findings demonstrate a structure-function relation that optimizes flow patterns in normal physiology, which can be compromised in venous valve disease. The results of this study provide valuable insights that improve the current understanding of blood flow patterns around venous valves and the design of future multiple paired prosthetic valves.

Post-fabrication QAC-functionalized thermoplastic polyurethane for contact-killing catheter applications.

The use of catheters is ubiquitous in medicine and the incidence of infection remains unacceptably high despite numerous advances in functional surfaces and drug elution. Herein we report the use of a thermoplastic polyurethane containing an allyl ether side-chain functionality (allyl-TPU) that allows for rapid and convenient surface modification with antimicrobial reagents, post-processing. This post-processing functionalization affords the ability to target appropriate TPU properties and maintain the functional groups on the surface of the device where they do not affect bulk properties. A series of quaternary ammonium thiol compounds (Qx-SH) possessing various hydrocarbon tail lengths (8-14 carbons) were synthesized and attached to the surface using thiol-ene "click" chemistry. A quantitative assessment of the amount of Qx-SH available on the surface was determined using fluorescence spectroscopy and X-ray photoelectron spectroscopy (XPS). Contact-killing assays note the Q8-SH composition has the highest antimicrobial activity, and a live/dead fluorescence assay reveals rapid contact-killing of Staphylococcus aureus (>75% in 5 min) and Escherichia coli (90% in 10 min) inocula. Scale-up and extrusion of allyl-TPU provides catheter prototypes for biofilm formation testing with Pseudomonas aeruginosa, and surface-functionalized catheters modified with Q8-SH demonstrate their ability to reduce biofilm formation.

Effect of artificial lung compliance on in vivo pulmonary system hemodynamics.

This study examined the effect of artificial lung compliance (C) on pulmonary system (PS) impedance and right ventricular function during in-series attachment of the MC3 Biolung in adult sheep. Compliances, C, of 0-20 ml/mm Hg were tested at the Biolung inlet. Results indicate the PS 0 harmonic input impedance modulus was not affected by C. The PS first harmonic input impedance modulus (Z1) was 10.9 +/- 3.2 mm Hg/(l/min) at C = 0 ml/mm Hg and minimized to 2.41 +/- 0.79 mm Hg/(l/min) at C > or = 0.5 ml/mm Hg. Cardiac output was 58% +/- 10% of its pre-Biolung attachment, baseline value at C = 0 ml/mm Hg and was maximized to an average of 75% +/- 11% at C > or = 0.5 ml/mm Hg. The left ventricular lateral-to-anteroposterior axis length ratio, which decreases with leftward septal shift, increased with C from 0.52 +/- 0.12 at C = 0 ml/mm Hg to 0.76 +/- 0.06 at C = 5 ml/mm Hg (p < 0.05), but decreased slightly with C at C > 5 ml/mm Hg. Therefore, the ideal C for right ventricular function is at least 0.5 ml/mm Hg and may be as high as 5 ml/mm Hg to minimize septal shift.

In vitro fluid mechanical effects of thoracic artificial lung compliance.

This in vitro study sought to determine what compliance minimizes thoracic artificial lung impedance and pump power output. A pulsatile pump drove 3.0 cP glycerol through a circuit consisting of an MC3 Biolung preceded by a piston-cylinder (PC, n = 5) chamber with a variable compliance or a polyurethane (n = 4) chamber with a fixed, yet pressure-dependent, compliance. Each chamber was tested at flow rates of 1.8, 3.0, and 5.0 l/min and heart rates of 60, 75, and 100 bpm. Compliances, C, from 0-20 ml/mm Hg were tested in the PC chamber. Instantaneous pump outlet flow and pressure were acquired for determination of device zeroth and first harmonic input impedance, Z(0) and Z(1), and pump steady and pulsatile output powers, P(s) and P(p). PC chamber results indicate that Z(0), Z(1), P(s), and Pp were minimized at C > 1, 5, 0.5, and 4 ml/mm Hg, respectively. This suggests that C should be 1 ml/mm Hg at minimum and ideally 5 ml/mm Hg. The polyurethane chamber was statistically similar to the PC chamber at C = 1 ml/mm Hg when comparing Z(0) and P(s), but was statistically inferior when comparing Z(1) and P(p). The polyurethane compliance chamber, therefore, should be redesigned with greater compliance.

Development of ambulatory arterio-venous carbon dioxide removal (AVCO2R): the downsized gas exchanger prototype for ambulation removes enough CO2 with low blood resistance.

We are developing an ultra compact gas exchanger to allow ambulation during arterial-venous CO2 removal (AVCO2R). The ambulatory AVCO2R gas exchanger (135 ml prime volume and 1.3 M2 gas exchange surface area) is made of polymethylpentene hollow fibers. The gas exchanger was attached to sheep carotid artery (12F) and jugular vein (14F) by percutaneous cannulae for 6 hours (n = 5). Device CO2 removal was measured and calculated at a constant blood flow rate of 1 L/min coupled with varying sweep gas from 1 to 15 L/min, and at constant sweep gas flow of 2 L/min coupled with varying blood flow from 0.5 to 1.25 L/min to determine capacity of CO2 removal at Pa CO2 = 40-50 mm Hg. Blood gases, CO2 removal and hemodynamics were recorded at 0, 3, and 6 hours. CO2 removal increased with sweep gas flow rate and with increase of device blood flow. Hemodynamics remained unchanged throughout study. Gas exchanger resistance remained stable at 2.3 +/- 0.53 mm Hg/L/min. CO2 removal with 1 L/min blood flow and 2 L/min sweep gas was 110 +/- 12 then stabilized at 85 +/- 14 mL/min to 6 hours. The compact ambulatory AVCO2R gas exchanger achieves stable, near total CO2 removal for at least 6 hours with a simple arteriovenous shunt.

Development of an artificial placenta: CO2 elimination and hemodynamics as a function of arteriovenous blood flow.

BACKGROUND: As a first step toward the development of an artificial placenta, we investigated the relationship between blood flow rate through an arteriovenous (A-V) circuit/oxygenator and both CO2 elimination and hemodynamic stability in a small animal model. METHODS: Male New Zealand rabbits (N = 10) with an average weight of 2.7 +/- 0.2 kg were anesthetized, paralyzed, and heparinized before carotid-jugular cannulation. A tracheostomy tube, an arterial catheter, and an aortic flow probe were placed. Arteriovenous flow through a custom-made, low-resistance, 0.5 m2 hollow fiber oxygenator was initiated. Oxygen sweep flow was maintained at 300 mL/min, whereas blood flow was controlled at 10 to 40 mL/(kg min). Ventilation was discontinued during each blood flow rate trial. Hemodynamic and preoxygenator and postoxygenator blood gas data were recorded 30 minutes after initiation of each flow rate. CO2 removal was the product of the oxygen sweep gas flow rate and the sweep flow exhaust CO2 content as determined by capnometry. Data were analyzed by analysis of variance with post hoc Dunnett's t test. RESULTS: CO2 removal increased and PaCO2 decreased as a function of A-V blood flow rate. Simultaneously, systolic blood pressure did not significantly change. CO2 removal was effective at device flows greater than 20% of cardiac output. CONCLUSION: In this rabbit model, A-V blood flows at 25% to 30% of cardiac output allow full gas exchange without hemodynamic compromise. This model raises the possibility of using A-V support and an artificial placenta in newborns with respiratory failure.

The paracorporeal artificial lung improves 5-day outcomes from lethal smoke/burn-induced acute respiratory distress syndrome in sheep.

BACKGROUND: Our low-impedence, paracorporeal artificial lung (PAL) prototype is well-tolerated in-series with the normal sheep pulmonary circulation. Using our lethal dose 80% to 100% smoke/burn acute respiratory distress syndrome (ARDS) sheep model, we compared PAL to volume-controlled mechanical ventilation (VCMV) in a prospective, randomized, controlled, unblinded, 5-day outcome study. METHODS: Fourteen sheep were randomized to PAL (n = 8) versus VCMV (n = 6) to assess outcome. For PAL, arterial cannulas were anastomosed to the proximal and distal main pulmonary artery with an interposing snare diverting full flow through a paracorporeal loop. Acute respiratory distress syndrome was induced in both groups (48 breaths smoke insufflation, third degree burn on 40% of total body surface area). When acute respiratory distress syndrome criteria were met (24 to 30 hours after injury), the PAL was interposed in the paracorporeal loop. Both groups were managed with a VCMV algorithm minimizing tidal volume, ventilator rate, and fractional inspired concentration of oxygen (FiO2). RESULTS: Six of eight PAL versus 1 of 6 VCMV sheep survived the 5-day study. In PAL, cardiac output, mean arterial pressure, pulmonary artery pressure, left atrial pressure, and central venous pressure remained stable. Average PAL gas transfer was 218.6 +/- 17.7 mL/min O2 and 183.0 +/- 27.8 mL/min CO2. Ventilator settings 48 hours after lung injury in PAL were significantly lower (p < 0.05) than VCMV (TV 210 versus 425 mL; respiratory rate 6 versus 29 breaths/min; minute ventilation 1.2 versus 10.8 L/min; FiO2 21 versus 100%). Likewise, PaO2/FiO2 ratio was normalized in PAL and still met acute respiratory distress syndrome criteria in VCMV. The PAL wet/dry ratio was significantly lower than VCMV (6.36 +/- 0.63 versus 11.85 +/- 1.54; p = 0.008). CONCLUSIONS: In a prospective, randomized, controlled, unblinded, outcomes study, PAL decreased ventilator-induced lung injury in a lethal dose 80% to 100% ARDS model to improve 5-day survival.