Silk production and global interest in the lustrous fiber date back to prehistoric times. Today, the natural protein is solidifying itself as a biomaterials alternative in the world of regenerative medicine.
A recent study conducted by Boston Children’s Hospital urologist Carlos Estrada, MD and bioengineer Joshua Mauney, PhD, shows two-layer, biodegradable silk scaffolds to be a promising cell-free, “off-the-shelf” alternative to traditional implants for the reconstruction of hollow gastrointestinal structures such as the esophagus.
Studying the new biomaterial
Investigators began researching silk and its potential use as a 3-D biomaterial in small and large animal models with urological defects in 2008. Their initial experiments found the protein fiber supported the formation of functional new tissue – without cell seeding – and degraded over time.
“Silk is attractive because it’s a naturally occurring polymer,” Estrada says. Silk is “tuneable,” he adds, because it takes on many forms including foams and weaves. It possesses high structural strength and elasticity, and provokes a minimal immune response when implanted.
Next-phase efforts are now focusing on the reconstruction of the esophagus and other tubular organs in the gastrointestinal tract, in collaboration with Rusty Jennings, MD, director of the Boston Children’sEsophageal Advanced Treatment Center.
According to Jennings, who treats a large population of children affected with esophageal atresia (a condition where portions of the esophagus are absent), an off-the-shelf silk graft would allow patients with this congenital defect to experience a less intrusive surgery with a quicker recovery time.
“There is a lot of potential here,” says Jennings of the 2014 study. “If we have to do an esophageal replacement, it requires several operations, which could take two whole days to perform. Being able to find a new option for the repair of the esophagus could potentially add great benefits to children.”
The various types of esophageal atresia, a condition in which infants are born missing part of the esophagus.
Positive research outcomes
The study, published in Biomaterials and presented this month at the 2015 Society For Biomaterials Annual Meeting and Exposition in Charlotte, NC, found that applying a silk “patch” to a rodent esophageal defect not only improved regenerative responses over conventional implants, but also supported the functionality of the newly generated conduit.
This translated into 90 percent survival rate post-surgery in the animals over the course of the 2-month study. Following a three day liquid diet, animals receiving silk implants were able to consume solid food and demonstrated similar degrees of weight gain as the control group.
The 3-to 5-year plan
Estrada and Mauney say the team will further test their scaffold in large animals with esophageal defects in hopes of moving into clinical trials in patients.
“If we are able to duplicate our previous findings in large-scale defects, we will take a crucial step in moving our silk scaffold technology toward clinical translation,” Mauney says. “It would be a dream for a surgeon to have a graft that you could take off-the-shelf in an operating room and implant in a child and have their function restored.”