Modulating physical properties of porcine urethra with injection of novel biomimetic proteoglycans ex vivo

Abstract

Urinary incontinence is a significant challenge for women who are affected by it. We propose augmenting the tissue structure to restore normal biomechanics by molecularly engineering the tissue using a novel family of biomimetic proteoglycans (BPGs). This work examines the ability of BPGs to modulate the mechanical and physical properties of porcine urethras ex vivo to determine the feasibility of BPGs to be implemented as molecular treatment for stress urinary incontinence (SUI). We investigated compliance by performing a unique radial expansion testing method using urethras from six- to nine-month-old pigs. The urethras were injected with 0.5 ml BPG solution at three sites every approximately 120° (conc.: 25 mg ml −1 , 50 mg ml −1 and 75 mg ml −1 in 1× phosphate-buffered saline (PBS); n = 4 per group) and compared them with PBS-injected controls. Young's modulus was calculated by treating the urethra as a thin-walled pressure vessel. A water uptake study was performed by soaking 10 mm urethra biopsy samples that were injected with 0.1 ml BPG solution (conc.: 50 mg ml −1 , 100 mg ml −1 and 200 mg ml −1 in 1× PBS; n = 6 per group) in 5 ml PBS for 24 h. Although there was no significant difference in Young's modulus data, there were differences between groups as can be seen in the raw radial expansion testing data. Results showed that BPGs have the potential to increase hydration in samples, and that there was a significant difference in water uptake between BPG-injected samples and the controls (100 mg ml −1 samples versus PBS samples, p < 0.05). This work shows that BPGs have the potential to be implemented as a molecular treatment for SUI, by restoring the diminished proteoglycan content and subsequently increasing hydration and improving the compliance of urethral tissue.