Liquid crystal elastomer based dynamic device for urethral support: Potential treatment for stress urinary incontinence

Abstract

Stress urinary incontinence (SUI) is characterized by the involuntary loss of urine due to increased intra-abdominal pressure during coughing, sneezing, or exercising. SUI affects 20-40% of the female population and is exacerbated by aging. Severe SUI is commonly treated with surgical implantation of an autologous or a synthetic sling underneath the urethra for support. These slings, however, are static, and their tension cannot be non-invasively adjusted, if needed, after implantation. This study reports the fabrication of a novel device based on liquid crystal elastomers (LCEs) capable of changing shape in response to temperature increase induced by transcutaneous IR light. The shape change of the LCE-based device was characterized in a scar tissue phantom model. An in vitro urinary tract model was designed to study the efficacy of the LCE-based device to support continence and adjust sling tension with IR illumination. Finally, the device was acutely implanted and tested for induced tension changes in female multiparous New Zealand white rabbits. The LCE device achieved 5.6% ± 1.1% actuation when embedded in an agar gel with an elastic modulus of 100 kPa. The corresponding device temperature was 44.9 °C ± 0.4 °C, and the surrounding agar temperature stayed at 42.1 °C ± 0.4 °C. Leaking time in the in vitro urinary tract model significantly decreased (p < 0.0001) when an LCE-based cuff was sutured around the model urethra from 5.2min ± 1min to 2min ±0.5min when the cuff was illuminated with IR light. Normalized leak point force (LPF) increased significantly (p = 0.01) with the implantation of an LCE-CB cuff around the bladder neck of multiparous rabbits. It decreased significantly (p = 0.023) when the device was actuated via IR light illumination. These results demonstrate that LCE material could be used to fabricate a dynamic device for treating SUI in women.

Keywords: Artificial muscle; Direct ink writing; Liquid crystal elastomers; Stress urinary incontinence.

Figure 1.

LCE-CB sling fabrication and actuation mechanism. A) Monomers used for synthesizing LC ink with embedded CB particles. B) Schematic of 3D printing fabrication of LCE-CB slings. C) Schematic of shape-morphing stimulus response of 3D printed LCE-CB slings. D) Photothermal actuation of 3D printed LCE-CB composite with IR light in the open air, scale bar: 5mm.

Figure 2.

Material Characterization. A) Representative DSC curves showing heat flow of LC ink without CB particles (yellow), 0.2 wt% CB concentration (Blue), and 0.4 wt% CB concentration (green) as a function of temperature. All three compositions exhibit an endothermic peak representing actuation (transition) temperature. B) Log-log plots of viscosity of the LC ink with 0 wt% – 0.4 wt% CB concentration as a function of shear rate at 38°C. C). Representative DMA curve showing storage modulus (solid blue) and tan delta (dashed red) as a function of frequency of a polydomain neat LCE sample. D) Heat actuation curve of rectangular 3D printed LCE samples with 0 wt% - 0.4 wt% CB concentration and uniaxial alignment along the short axis of the rectangle. Three samples are evaluated from three different batches for each composition (n=9). Error bars represent standard deviation. (E) Phase contrast micrographs of hDFAs at 0, 24, and 48 hours in the control, LCE extract and tygon extract media. Scale bars = 100 μm. (F) Representative fluorescent micrographs of the Live(green)/Dead(red) assay for hDFAs after 48 hours in control, LCE-CB extract or Tygon extract media. Scale bars = 100 μm. Quantification of live cell percentage for control, LCE-CB extract and tygon extract media conditions after 48 hours. Results shown are mean with standard error of mean. Statistical significance is noted as: ****p<0.0001, one way ANOVA. (n=3).

Figure 3.

Shape Change of LCE-CB sample with varying CB concentrations in response to varying IR light intensities. A) Schematic showing the setup used to analyze the shape change and temperature response of the LCE-CB sample in response to IR light. B) Photothermal actuation curve of neat LCE and LCE-CB sample with varying CB concentrations embedded in 0.5% agar in response to varying IR light intensities. C) Temperature measurement of neat LCE and LCE-CB samples with varying CB concentrations embedded in 0.5% agar in response to varying IR light intensities. Temperatures are measured at the sample surface and agar surrounding the sample (2mm vicinity) after 2 minutes of continuous IR light irradiation. D) Images showing contraction along the width and elongation along the length, as well as temperature of the sample (TS) and surrounding agar (TA) of an LCE-CB sample with 0.4 wt% CB embedded in 0.5% agar gel. LCE-CB sample at 0 seconds with IR off (left), sample actuation and temperature measured after irradiation with 500 mW/cm² IR light for 120 seconds (middle), and sample actuation and temperature measured after irradiation with 800 mW/cm² IR light for 120 seconds (right). Three samples are evaluated from three different batches for each composition (n=9 for each composition). Error bars represent standard deviation. Scale bar: 1mm.

Figure 4.

Shape Change of LCE-CB sample in scar-tissue-like environment A) Photothermal actuation curves of LCE-CB sample with 0.4 wt% CB embedded in agar gels with varying agar concentration measured over 2 minutes of continuous 500mW/cm² IR light irradiation. C) Temperature measurement of LCE-CB sample embedded in agar gels with varying agar concentration measured after 2 minutes of continuous 500mW/cm² IR light irradiation. Temperatures are measured at the sample surface (TS) and agar surrounding the sling (TA) (2mm vicinity) after 2 minutes of continuous IR light irradiation. D) Images showing contraction along the width and elongation along the length and temperature of the sample and surrounding agar of an LCE-CB sling with 0.4 wt% CB embedded in 1% agar gel. LCE-CB sample at 0 seconds with IR off (left), sample actuation and temperature measured after irradiation with 500 mW/cm² IR light for 60 seconds (middle), and sample actuation and temperature measured after irradiation with 500 mW/cm² IR light for 120 seconds. Three samples are evaluated from three different batches in each agar gel (n=9 for each composition). Error bars represent standard deviation. Scale bar: 1mm.

Figure 5.

Actuation curve and cyclic actuation of LCE-CB sample. A) Actuation onset and offset of an LCE-CB sample with 0.4 wt% CB concentration embedded in 1% agar Illuminated with 500 mW/cm² intensity IR light. IR light is on for 90 seconds, then off for 60 seconds B) Cyclic Actuation of LCE-CB sample with 0.4 wt% CB embedded in 1% agar gel. C) Corresponding temperature of the device (blue solid line) and surrounding agar (yellow dashed line) during the cyclic actuation test. Embedded samples are irradiated with 500 mW/cm² IR light for 2 mins, then allowed to return to the original shape over 60 seconds. This test is repeated over 100 cycles. (n=1). Error bars represent standard deviation.

Figure 6.

Actuation of LCE-CB cuff in an in vitro urinary tract model. A) Image showing the in vitro urinary model B) Images showing snapshots of a model urethra with no LCE-CB cuff around (left), with LCE-CB cuff around the urethra and IR light off (Middle), and with LCE-CB cuff around the urethra and IR light on condition (right). A slab of 1% agar gel cut in the negative shape of the model urethra is placed on top of the urethra to mimic tissue surrounding the urethra. C) Duration of time necessary for the model urethra to void 19mL of water with no LCE-CB cuff, with LCE-CB cuff and IR light off, and with LCE-CB cuff and IR light on conditions. Three different LCE-CB cuffs were tested over three voiding cycles. Data from each cycle is represented in a different color. A p-value less than 0.05 was considered statistically significant. D) One LCE-CB cuff is tested over 15 cycles of voiding in the IR light off and IR light on conditions, and voiding time for 19 mL of water is recorded. (n=1). Error bars represent standard deviation. Statistical significance is noted as: *p=0.0397, one way ANOVA.

Figure 7.

LCE-CB cuff analysis in multiparous rabbit. A) Schematic illustrating the catheterization of rabbit bladder using a butterfly catheter. B) Image of rabbit bladder and bladder neck exposed. C) Image showing an LCE-CB cuff implanted around the rabbit bladder neck. D) Snapshot of force applied to rabbit abdomen on top of the bladder dome. E) Box plot showing normalized abdominal force required to cause leakage at baseline, after device implantation (Implant), during IR actuation (Implant +IR ON), and redo of the implant with IR off condition (Implant + IR OFF). Data from each experimental replicate is presented in a different color. Statistical significance is noted as: *p=0.0231 (implant vs. implant + IR ON), *p=0.0138 (baseline vs. implant) paired t test. (n=3 with five repeat measurements for each study group in each animal). Error bars represent standard deviation.