UCLA-developed biomaterials address challenges of lower urinary tract surgery

To address challenges in repairing and replacement of lower urinary tract (LUT) tissues, Renea M. Sturm, MD, FAAP, assistant professor of urology at the David Geffen School of Medicine at UCLA, has led the development of an innovative biomaterial scaffold and adhesive patch.

Both are elastic and biodegradable, overcoming limitations of current materials used for these procedures.

The scaffolds, subject of a recently published article, were developed with Nasim Annabi, PhD, associate professor of chemical and biomolecular engineering at UCLA.

They incorporate a combination of a gelatin to improve handling and biomechanics with an elastin-like peptide, a protein with intrinsic disorder encoded at the molecular level that increases the elasticity of many tissues. 

These features are harnessed to mimic the natural viscoelasticity of the urinary bladder and urethra, allowing them to engage in cyclic extension with minimal energy loss.

A multidisciplinary approach

Dr. Sturm’s foray into these new materials began more than five years ago at UCLA. She presented the unique challenges of the lower urinary tract to her engineering colleagues. which led to the establishment of a development team.

Team co-leader Ali Khademhosseini, PhD, CEO of the Terasaki Institute and former professor of bioengineering, chemical engineering and radiology at UCLA, had begun work on a biodegradable, flexible adhesive patch (BLAP) for urinary bladder suture reinforcement. 

The results of that effort, also published this year, are unique for their development of a tensile-matched patch with a functionalized adhesive surface. It binds with tissues in a similar manner to that used by mussels to adhere in moist environments.

Both efforts reflect Dr. Sturm’s strong underlying belief in the need for elastic biomaterials inspired by the LUT’s unique form and function. However, many materials or tissues that have been previously used to augment, support or replace LUT tissue, lack that viscoelasticity. 

“The bladder and urethra are organs that cycle multiple times a day, and thousands of times throughout a lifetime,” she says. “And it’s extreme cycling; the bladder routinely goes from empty to holding 400 ml.” 

UCLA’s newly developed biomimetic, suturable and extensible scaffolds are made of a fibrous mat comprised of two naturally derived polymers. And while the materials handle similarly to native tissue, the scaffolds are not a support layer alone. 

“They also provide biologic and structural cues for tissue regeneration as the scaffolds degrade over time,” says Dr. Sturm.

BLAP, too, addresses a glaring lack of flexibility with suture reinforcement, as the staples and other material used on suture lines can’t expand or contract with the urinary cycle.

The patch aims to prevent tissue failure at suture lines — a cause of complications and readmissions following complex LUT surgeries.

“We wanted to ensure tissue support, but also the flexibility to allow LUT organs to have a catheter removed and return to function more rapidly than current techniques,” explains Dr. Sturm. 

Clinical motivation

A specialist in pediatric urology, Dr. Sturm sees children in her practice who lack functional LUT tissues, particularly due to developmental differences. A common condition to which this applies is hypospadias, a congenital condition affecting the anterior male urethra and penile development. 

For proximal or complex cases, tissue from the foreskin or the inner cheek is used to reconstruct or build a new urethra, often in a multi-staged procedure. 

“But these tissues do not have the same biologic, structural or mechanical properties as a healthy urethra, a factor that may impact its long-term functionality,” Dr. Sturm says. 

Similarly, children and youth may require bladder reconstruction due to a neurogenic bladder (innervation of the bladder impacted by spina bifida or spinal cord injury), or bladder malignancy or exstrophy (deficient anterior bladder and abdominal wall). 

“If we need to augment or replace the bladder, we often use the bowel,” says Dr. Sturm. “Again, it’s not matched in biology or function, as it is absorptive, mucous-producing, and has differing biomechanics and structure than the urinary bladder. Children who undergo these procedures have a high risk of both early and late complications.” 

Dr. Sturm notes that UCLA’s recent participation in the first human bladder transplant provides hope for select patients – however, it is critical to continue developing degradable structural material that can minimize the need for long-term immunosuppression.

Filling a gap

The materials have been extensively characterized to determine the precise formulations that most closely resemble urinary tract target tissues, degradation and suturability. 

These were evaluated in vitro using human LUT cell lines, followed by biocompatibility assessment in animal models. The team has recently expanded the biomaterial formulations and are completing implantation in functional models. 

“One of our next steps includes adding specific proteins,” Dr. Sturm says. “They can be released from the scaffold layer in a timed or patterned fashion to further support microenvironments that help establish functional tissues.”

Aware that prior attempts by others have led to failed biomaterials, Dr. Sturm notes none have been translated to clinical use. Why is this one different? 

“Many advances in material science allow us to better understand the microenvironments within tissue and modify them in a more precise way,” she says. “We're applying the latest insights around modern biomaterials methods to the LUT. 

We consider structure, mechanics, degradation, suturability and regenerative capacity of the material. We’re also examining its potential to centrally vascularize and minimize risk of fibrosis early in the process.” 

The initial steps of identifying, characterizing and evaluating the biocompatibity of these novel materials are vital steps toward future clinical application, Dr. Sturm says.

We’re excited to continue focusing on all aspects of these materials to meet the needs of a range of LUT conditions in children and adults.”