Stress urinary incontinence (SUI) affects 13 million people in the United States per year [2], and some studies have suggested that at least 2% of healthcare costs result from urinary incontinence [3]. Although not a life- threatening condition, the personal cost associated with the condition, and quality-of-life improvement possible with successful treatment, make this a highly addressable condition. In addition, the relatively straightforward treatment options available, make permanent treatment strategies very desirable. Most desirable would be an approach that permanently displaces the tissue, restoring function and avoiding recurrence. An effective tissue-bulking agent for stress urinary incontinence should be non- immunogenic, biocompatible, non-toxic, and hypo-allergenic. It must also exhibit anatomical integrity, integrate with local tissues with minimal inflammation, maintain its injected volume, exhibit no migration outside of the intended bulking area, and be easy to use as well as cost effective. An injectable viscoelastic material that physically bulks the tissue would be ideal. This proposal describes the continued development of a material suitable for tissue bulking to treat stress urinary or fecal incontinence. The existing principle technology is a novel method that uses existing biocompatible materials to form a hydrogel from an injectable liquid without a chemical reaction thus making the formulation inert, truly biocompatible and tissue friendly.
Our specific aims will address the following requirements for an injectable poly(vinyl alcohol) (PVA) system as a tissue-bulking agent for treatment of stress urinary incontinence and fecal incontinence: 1. to exist as a liquid pre-gel that can be injected safely through a narrow gauge needle;2. to gel at under physiological conditions (temperature, medium);3. to be space-filling;4. to resist migration;5. to have minimal inflammatory response.
Specific Aim 1 : The basic requirements and properties of the pre-gel will be determined using non-gelling PVA solutions. The outcomes of Specific Aim 1 will be functional specifications for the rheological properties of the pre-gel for the target application.
Specific Aim 2 : Gelling systems will be considered, specifically, investigation of the effects of concentration, molecular weight, and sterilization on the gelation kinetics and viscosity of a set of hydrogels. The outcome of Specific Aim 2 will be a selection of target formulations that meet the functional specifications of SA1 and that have fully characterized rheological responses.
Specific Aim 3 : Optimal hydrogel formulations developed in Specific Aim 2 will be screened after gamma sterilization for injectability, gelation and safety. Those formulations that pass these tests, are injectable and gel at 400C will be considered for use in Specific Aim 4.
Specific Aim 4 : 3-4 biocompatible, injectable formulations that possess suitable gelation kinetics will be selected for bench-top space-filling, gelation, and retention analysis. A rat model will be used to validate safety over the period of at least 12 weeks. The outcome from this project will be at least one formulation of injectable PVA hydrogel that is proven safe in short-term in vitro and in vivo tests and that has passed mechanical criteria sufficient for tissue bulking in SUI. The formulation and testing outlined here will provide a foundation for future work in an anticipated Phase II project.
Stress urinary incontinence afflicts approximately 13 million people in the U.S. and is associated with discomfort and embarrassment. This issue can severely impact the quality of life of otherwise healthy individuals, and is often associated with a relatively easily addressed dysfunction of the muscles surrounding the urinary tract. Current treatment options available today include tissue bulking agents to restore muscle position, but many of the products currently available provide only short term solutions that require recurrent injections and multiple surgical visits and have only a limited implant life. The research proposed here will further develop an innovative injectable hydrogel material that is both biocompatible and non-degradable for use as a tissue bulking agent to treat stress urinary incontinence.
