In vivo molecular engineering of the urethra for treatment of stress incontinence using novel biomimetic proteoglycans.

Stress urinary incontinence (SUI), a serious condition which affects ~56% of postmenopausal women, is the involuntary leakage of urine through urethra during physical activity that causes an increase in abdominal pressure. SUI is associated with a decrease in compliance and volume of urethral tissue, likely due to a reduced proteoglycan: collagen ratio in the extracellular matrix and collagen disorganization. Here, we investigated the use of biomimetic proteoglycans (BPGs) to molecularly engineer urethral tissue of New Zealand White rabbits to examine biocompatibility in vivo. BPG concentrations of 50 mg/mL (n = 6, 1 week) and 200 mg/mL (n = 6, 1 week and n = 6, 6 weeks) dissolved in 1× phosphate-buffered saline (PBS) were injected transurethrally using a 9 French cystoscope, and were compared to PBS-injected controls (n = 3, 1 week) and non-injected controls (n = 2, 1 week). Urethral compression pressure measurements confirm BPG injections did not modify normal urethral pressure, as intended. Histological assessment demonstrated biological tolerance of BPGs in urethra and no inflammatory response was detected after 1 and 6 weeks compared to non-injected controls. Confocal imaging of fluorescently-labeled BPG injected urethral specimens demonstrated the integration of BPGs into the interstitial connective tissue and confirmed they were still present after 6 weeks. A general decrease of collagen density was exhibited near injection sites which may be due to increased hydration induced by BPGs. Injection of BPGs is a novel approach that demonstrates potential as molecular treatment for SUI and may be able to reverse some of the degenerative tissue changes of individuals affected by this condition. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: 00B: 000-000, 2019. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2409-2418, 2019.