A cell-free, silk-based scaffold for regenerating bladder tissue

This regenerative medicine technology was selected as one of 2013 Technology Development Fund projects.

Scanning electron microscopy image
of bi-layer silk scaffold structure

In the 1990’s, Anthony Atala, MD, who became head of the Institute for Regenerative Medicine at Wake Forest after undertaking pioneering work in tissue engineering in Boston Children’s Urology Department, set out to grow new or augment bladders for patients because they suffered from neurogenic bladder (due to spina bifida, spinal cord injuries, multiple sclerosis, Parkinson’s and other diseases) as well as bladder cancer.

Dr. Atala developed a revolutionary approach to bladder augmentation by implanting a “cellularized” scaffold from biocompatible materials seeded with a patients’ own cells. While initial results of this work were promising, limitations began to emerge with this approach.

Carlos Estrada, MD, a urologist at Boston Children’s, and Joshua Mauney, PhD, learned from this initial work. Cellularization is the most complex part of the original strategy, Estrada asserts, and cells taken from diseased bladders “do not always function appropriately.” Based on this understanding, Estrada and Mauney sought a new biomaterial that required “no cells at all” to generate tissue.

A new biomaterial

They turned to silk. Rather than using cells to augment the bladder, a complicated process, silk could provide an “off the shelf” option, says Carlos Estrada, MD, a urologist at Boston Children’s Hospital.

Recent research by Estrada and Mauney shows that scaffolds made of fibroin (the protein that makes up raw silk) have worked well in augmenting bladders in animal models—without the need for cells.

“Silk is attractive, because it’s a naturally occurring polymer,” Estrada says. Also, silk is “tuneable” and can take on many forms, including foams and weaves. “It can be elastic, porous or stiff—whatever you need.”

For bladder augmentation, he says, “you want a material that will provide physical support initially for the defect site but will gradually be replaced by host tissue over time.”

With this in mind, Estrada, Mauney and their colleagues imported silk worms from Asia, then boiled down the silk to remove the protein sericin, which is immunogenic and could trigger an allergic reaction. What remains is inert and biodegradable, yielding scaffolds that are “strong and elastic but also capable of degrading to allow for tissue regeneration,” Estrada reports.

Together, Mauney and Estrada have produced a novel bi-layer silk scaffold, comprised of a foam layer that allows for ingrowth of host tissues and a non-porous layer that seals the wound site.

For their initial experiments, they placed the scaffolds in rodents with urinary tract defects. “We found that the scaffolds degraded over time while supporting the formation of functional new tissue,” Estrada says. The same was true in larger animals such as pigs.

Beyond the bladder

The researchers are excited to have found “an acellular platform permissive for tissue regeneration,” Estrada says. He hopes the technique will replace the current technique for bladder augmentation, a complex, open procedure in which a portion of the intestine or stomach is attached to the bladder as a patch. Moreover, he sees the new approach as having uses beyond the bladder: “We may be able to use these scaffolds in the urethra, esophagus, trachea—any of the hollow organs.”

In the meantime, the team is further testing their scaffold in animals with bladder defects, with support and funding by Boston Children’s Technology Development Fund. They hope that clinical trials on human patients with will begin within five years.

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