Bulking agents are space-filling injectable substances used to increase tissue bulk. They can be injected periurethrally to treat urinary incontinence and perianally to treat fecal incontinence. A number of products have been developed, and there are several U.S. Food and Drug Administration (FDA)-approved options for treating urinary incontinence. One product is commercially available to date for treating fecal incontinence. When used to treat stress urinary incontinence (SUI), bulking agents are injected periurethrally to increase the tissue bulk and thereby increase resistance to the outflow of urine. The bulking agent is injected into the periurethral tissue as a liquid that then solidifies into a spongy material to bulk the urethral wall. Bulking agents may be injected over a course of several treatments until the desired effect is achieved. Periurethral bulking agents have been widely used for incontinence in women. Men have also been treated, typically those with post-prostatectomy incontinence.
Following the success of periurethral bulking agents for treating SUI, bulking agents injected into the anal canal have been proposed for treating fecal incontinence. In particular, bulking agents are a potential treatment for passive fecal incontinence associated with internal anal sphincter (IAS) dysfunction. The bulking agent is injected into the submucosa of the anal canal to increase tissue bulk in the area, which narrows the opening of the anus. Current treatment options for fecal incontinence include conservative measures e.g., dietary changes, pharmacotherapy and pelvic floor muscle exercises, sacral nerve stimulation, and surgical interventions to correct an underlying problem.
Key factors in determining the optimal product are biocompatibility, durability, and absence of migration. A number of periurethral bulking agents to treat urinary incontinence have been cleared for marketing by the U.S. Food and Drug Administration (FDA). Except for Contigen®, bulking agents are indicated by FDA for use only in women, specifically those with stress urinary incontinence due to intrinsic sphincter deficiency. Cross-linked collagen (e.g., Contigen®) has been commercially available for many years. Collagen is slowly absorbed over time, and symptoms may recur, requiring additional injections. Other periurethral bulking agents cleared by the FDA for urinary incontinence include carbon-coated beads (e.g., Durasphere®), spherical particles of calcium hydroxylapatite (CaHA) in a gel carrier (Coaptite®), polydimethylsiloxane (silicone, Macroplastique®), and ethylene vinyl alcohol copolymer implants (e.g., Uryx®, marketed under the trade name Tegress® starting in 2005). Tegress was later voluntarily removed from the market due to safety concerns.
Several agents identical to or similar to those used for urinary incontinence e.g., Durasphere, silicone biomaterial, etc. have been studied for the treatment of fecal incontinence. To date, only one bulking agent has been approved by the FDA for treating fecal incontinence. This is a formulation of non-animal stabilized hyaluronic acid/dextranomer in stabilized hyaluronic acid (NASHA Dx) and is marketed by Q-Med as Solesta. A hyaluronic acid/dextranomer formulation (Deflux™) from the same company has been commercially available for a number of years for the treatment of vesicoureteral reflux in children.
Autologous fat and autologous ear chondrocytes have also been used as periurethral bulking agents; autologous substances do not require FDA approval. Polytetrafluoroethylene (Teflon®) has been investigated as an implant material but has not received FDA approval. A more recently explored alternative is cellular therapy with myoblasts, fibroblasts, or stem cells (muscle-derived or adipose-derived). In addition to their use as periurethral bulking agents, it is hoped that transplanted stem cells will undergo self-renewal and multipotent differentiation, which could result in regeneration of the sphincter and its neural connections.
Several periurethral bulking agents have been approved by the U.S. Food and Drug Administration (FDA) through the premarket approval process for the treatment of stress urinary incontinence due to intrinsic sphincter deficiency; other than Contigen, approval is only for use in adult women. Products include:
- In 1993, Contigen (Allergan, Inc.), a cross-linked collagen, was approved. A supplemental approval in 2009 limited the device’s indication to treatment of urinary incontinence due to intrinsic sphincter deficiency in patients (men or women) who have shown no improvement in incontinence for at least 12 months.
- In 1999, Durasphere (Advanced UroScience), pyrolytic carbon-coated zirconium oxide spheres, was approved.
- In 2004, Uryx (CR Bard), vinyl alcohol copolymer implants, was approved. In 2005, approval was given to market the device under the trade name Tegress. In 2007, Tegress was voluntarily removed from the market due to safety concerns.
- In 2005, Coaptite (BioForm Medical, Inc.), spherical particles of calcium hydroxylapatite, suspended in a gel carrier, was approved for soft tissue augmentation in the treatment of stress urinary incontinence due to intrinsic sphincter deficiency in adult females.
- In 2006, Macroplastique (Uroplasty), polydimethylsiloxane, was approved.
- One bulking agent was approved by the FDA through the premarket approval process for treating fecal incontinence. In 2011, non-animal stabilized hyaluronic acid/dextranomer in stabilized hyaluronic acid (NASHA Dx) marketed as Solesta® (Q-Med) is indicated for the treatment of fecal incontinence in patients 18 years and older who have failed conservative therapy.