Rory Mooney

Augmentation Cystoplasty and Extracellular Matrix Scaffolds: An Ex Vivo Comparative Study with Autogenous Detubularised Ileum

Background Augmentation cystoplasty (AC) with autogenous ileum remains the current gold standard surgical treatment for many patients with end-stage bladder disease. However, the presence of mucus-secreting epithelium within the bladder is associated with debilitating long-term complications. Currently, decellularised biological materials derived from porcine extracellular matrix (ECM) are under investigation as potential augmentation scaffolds. Important biomechanical limitations of ECMs are decreased bladder capacity and poor compliance after implantation. Methodology/Principal Findings In the present ex vivo study a novel concept was investigated where a two-fold increase in ECM scaffold surface-area relative to the resected ileal segment was compared in ovine bladder models after AC. Results showed that bladder capacity increased by 40±4% and 37±11% at 10 mmHg and compliance by 40.4±4% and 39.7±6% (ΔP = 0–10 mmHg) after AC with ileum and porcine urinary bladder matrix (UBM) respectively (p<0.05). Comparative assessment between ileum and UBM demonstrated no significant differences in bladder capacity or compliance increases after AC (p>0.05). Conclusions These findings may have important clinical implications as metabolic, infective and malignant complications precipitated by mucus-secreting epithelium are potentially avoided after augmentation with ECM scaffolds.

Preventing Urethral Trauma from Inadvertent Inflation of Catheter Balloon in the Urethra during Catheterization: Evaluation of a Novel Safety Syringe after Correlating Trauma with Urethral Distension and Catheter Balloon Pressure

PURPOSE We investigated urethral diametric strain and threshold maximum inflation pressure for rupture during inadvertent inflation of a catheter anchoring balloon in the urethra. In addition, we evaluated a novel safety device to prevent trauma based on these parameters. MATERIALS AND METHODS Inflation of a urethral catheter anchoring balloon was performed in the bulbar urethra of 21 ex vivo porcine models using 16Fr catheters. Urethral trauma was assessed with retrograde urethrography. Urethral rupture was correlated with internal urethral diametric strain and maximal urethral pressure threshold values in kPa. Urethral catheters were then inflated in the bulbar urethras of 7 fresh male cadavers using a standard syringe and a prototype syringe. The plunger of the standard syringe was depressed until opposing resistance pressure generated by the urethra prevented further inflation of the anchoring balloon. The plunger of the prototype safety syringe was depressed until sterile water in the syringe decanted through an activated safety threshold pressure valve. RESULTS Retrograde urethrography demonstrated that porcine urethral rupture consistently occurred at an internal urethral diametric strain greater than 40% and a maximum inflation pressure greater than 150 kPa. The mean ± SD maximum human urethral threshold inflation pressure required to activate the safety prototype syringe pressure valve was 153 ± 3 kPa. In comparison, maximum inflation pressure was significantly greater using the standard syringe than the activated prototype syringe (mean 452 ± 188 kPa, p <0.001). CONCLUSIONS Internal urethral diametric strain and threshold maximum inflation pressures are important parameters for designing a safer urethral catheter system with lower intrinsic threshold inflation pressures.

Cell-seeded extracellular matrices for bladder reconstruction: An ex vivo comparative study of their biomechanical properties

Purpose Autogenous ileal tissue remains the gold-standard biomaterial for bladder replacement purposes; however, cell-seeded extracellular matrix (ECM) scaffolds have shown promise. Although the biological advantages of cell-seeded ECMs in urological settings are well documented, there is a paucity of data available on their biomechanical properties. In this study, the biomechanical properties of cell-seeded ECMs are compared with autogenous ileal tissue. Methods Human urothelial cells (UCs) and smooth muscle cells (SMCs) were obtained by bladder biopsy and cultured onto porcine urinary bladder matrix (UBM) scaffolds under dynamic and static growth conditions for 14 days. The biomechanical properties of cell-seeded UBM (n = 12), and porcine ileum (n = 12) were determined with uni-axial tensile testing protocols and compared with stress-strain curves. In addition, their biomechanical properties were compared with porcine bladder tissue (n = 12) and unseeded UBM (n = 12). Results There were significant differences in the biomechanical properties of each biomaterial assessed. Strain to failure occurred at 92 ± 24% for dynamically cultured cell-seeded UBM compared to 42.2 ± 5.20% for ileal tissue (p<0.01). Values for linear stiffness at 30% strain were significantly lower in dynamically cultured cell-seeded UBM compared to ileal tissue (0.36 ± 0.14 MPa versus 0.67 ± 0.32 MPa respectively, p<0.01). Bladder tissue remained the most distensible biomaterial throughout, with linear stiffness measuring 0.066 ± 0.034 MPa at 30% strain. Conclusions Dynamically cultured cell-seeded ECMs are biomechanically superior to ileal tissue for bladder replacement purposes. Additional comparative in vivo studies will be necessary before their role as a reliable alternative is clearly established.

Characterisation of human urethral rupture thresholds for urinary catheter inflation related injuries

Data on urethral catheter related injuries is sparse. In this study we aimed to characterise urethral diametric strain and urinary catheter inflation pressure thresholds that precede human urethral trauma during urethral catheterisation (UC). Human urethras were obtained from patients undergoing male to female gender reassignment surgery [(n = 9; age 40 ± 13.13 (range: 18-58)) years]. 12Fr urinary catheters were secured in the bulbar urethra and the catheters anchoring balloon was inflated with a syringe pump apparatus. Urethral diametric strain and balloon pressure were characterised with video extensometry and a pressure transducer respectively. Immunohistochemistry, Massons trichrome and Verhoeff-Van Gieson stains evaluated urethral trauma microscopically. Morphological characterisation of the urethral lumen was performed by examining non-traumatised histological sections of urethra and recording luminal area, perimeter and major/minor axis length. Tearing (n = 3) and rupture (n = 3) of the urethra were observed following catheter balloon inflation. The threshold for human urethral rupture occurred at an external urethral diametric strain ≥ 27% and balloon inflation pressure ≥ 120kPa. Significant relationships were identified between urethral wall thickness and the level of trauma induced during catheter balloon inflation (p = 0.001) and between the pressure required to inflate the catheter balloon and the length of the major axis of the urethral lumen (p = 0.004). Ruptured urethras demonstrated complete transection of collagen, elastin and muscle fibres. In conclusion, urethral rupture occurs at an external urethral diametric strain ≥ 27% or with balloon inflation pressures ≥ 120 kPa. Incorporation of these parameters may be useful for designing a safety mechanism for preventing catheter inflation related urethral injuries.