A novel waterjet technology for transurethral cystoscopic injection of viable cells in the urethral sphincter complex

Abstract

Aims: In a recent preclinical study, we noticed that injection of cells in the urethral sphincter by needle through a cystoscope under visual control frequently yielded in misplacement or loss of cells. We, therefore, investigated if a needle-free waterjet device delivers viable cells under defined settings, including injection volume and pressure, fluid velocity and transportation media, precisely through the urothelium and connective tissue close to the sphincter muscle without full penetration of the sphincter apparatus. Methods: Mesenchymal stromal cells (MSCs) were prepared for needle-free waterjet injections. Upon injections into liquids cell viability and yield were investigated by trypan blue dye exclusion. Upon injection into cadaveric urethral tissue samples, cells were isolated from the urethrae and expanded to prove that this novel method delivered viable cells into the tissue. MSC injections by William's needle served as controls. Results: Waterjet injections of MSCs into isotonic cell culture medium resulted in equal or better yields of viable cells when compared with needle injections.Upon injection in urethral tissue samples, the waterjet technology facilitated fast and precise injections of viable cells through urothelial, mucosal and submucosal layers to reach the sphincter muscle. By controlling the injection pressure, loss of cells due to insufficient thrust or unintended full penetration was avoided.Conclusions: Needle-free waterjet injections deliver cells in the urethra faster and more precisely when compared with needle injections without compromising their viability. This is the first proof-of-concept study providing evidence that a waterjet transports viable cells precisely into the targeted tissue. K E Y W O R D S cell injection, cell therapy, medical technology, stress urinary incontinence, waterjet ---This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.Abbreviations: E, effect = pump setting, reflects a given pressure in an open system; IPCM, improved pressure control mode; LSM, laser scanning microscope; MSC, mesenchymal stromal cells; SUI, stress urinary incontinence; UPaCS, upgraded pump and controller system (based on ERBEJET 2).

Hydrojet-based delivery of footprint-free iPSC-derived cardiomyocytes into porcine myocardium

“…These results were not unexpected, as higher pressures correlate positively with velocity and, accordingly, increased shear stress which facilitates cell disruption 33 . Similar results have recently been shown for the injection of MSCs into the urinary sphincter complex 32 .…”

“…A modified ERBEJET ® 2 from Erbe Elektromedizin GmbH (Tuebingen, Germany) was used to apply cells and microparticles into the porcine heart muscle. The new hydrojet system 32 allowed the generation of pressures (E = effects) ranging from E5 to E80 while enabling a rapid and accurate change between tissue penetration pressures and cell injection pressures. First, using a “tissue penetration jet”, 1 ml 0.9% NaCl solution was applied with high pressures E60 or E80 to penetrate the heart tissue.…”

“…However, covering a large area of myocardial infarction may require multiple injections, leading to procedural damage to the myocardium 31 and should, therefore, be avoided. Recently, Jäger et al 32 described a hydrojet-based method for the delivery of MSCs into urethral tissue. They demonstrated a better yield of viable cells compared to needle injections with a fast and precise injection of viable next to or into the sphincter muscle.…”

Simulation of the Dynamic Characteristics of High-Speed Waterjet Using SIMULINK

“…Based on the above features of the SIMULINK software, the dynamic characteristics of the hydraulic system were simulated. According to Formulas (1)- (7), with the help of the visualization tools provided by SIMULINK, a SIMULINK simulation model was constructed. Formula (1) was encapsulated in the flow equation module of the electromagnetic valve; Formula (2) was encapsulated in the flow equation module of the oil inlet chamber of the pressure cylinder; Formula (4) was encapsulated in the force balance equation module of the pressurizer; Formula (5) was encapsulated in the flow equation module of the drainage chamber of the pressurizer; Formula (6) was encapsulated in the flow equation module of the energy accumulator; Formula (7) was encapsulated in module of the energy accumulator system, as shown in Figure 1.…”

“…Waterjet systems usually adopt two kinds of ultra-high pressure generators: one kind is plunger pump that could be driven directly, the other kind is hydraulic pressure cylinder. Generally speaking, the directly-driven plunger pump has a higher efficiency, while the hydraulic pressure cylinder can generate higher pressure (which is decided by the pressure ratio) [7,8]. In fact, for both kinds of the ultra-high pressure generators, the instantaneous output pressures are pulsing, so the outlet velocity of the formed waterjet is unstable [9][10][11][12][13][14].…”