Hopkins team seeks to improve reconstructive surgeries

Justin Sacks, a plastic surgeon at Johns Hopkins, has performed thousands of reconstructive surgeries. But he could not accept being unable to make a person whole again. For example, women in treatment for early-stage breast cancer often consider tissue-conserving lumpectomies or partial mastectomies, in which surgeons remove the tumor and some surrounding tissue. While therapeutically effective, such procedures can leave visible defects. Yes, the cancer has been removed. The patient has been healed. But part of her is missing. Similarly, soldiers wounded in battle may live out the rest of their lives with visible reminders of what was taken from them.

Sacks envisioned a three-dimensional soft tissue—a polite term for fat—that physicians could cut to order to fill a cavity. In July 2013, he and like-minded surgical resident Sashank Reddy reached out to engineering colleague Hai-Quan Mao, who initially wondered whether the idea was feasible. Any doubts were short-lived, however, as Mao and his team embraced the challenge and made Sacks' vision a reality. A team of Johns Hopkins biomedical engineers, led by Mao, has developed a synthetic, implantable 3-D soft tissue scaffold, for which they've applied for a provisional patent. In rodent studies, the composite material has served as a framework for the body's native fatty tissue and blood vessels to grow and fill in the defect. Afterward, the implanted scaffolding naturally degrades, leaving the new tissue intact. "I like to think of the material as a conducive template, attracting both growth cues and cells from the surrounding tissue to regenerate," Mao says.

Composites, both biological and synthetic, have become a prime target for tissue engineers. The Johns Hopkins team opted for a synthetic material made from degradable polymer nanofibers that look like a nest of sticklike filaments, suspended in a viscous and biodegradable hydrogel commonly used in injectable cosmetic fillers to erase wrinkles and plump up lips. The nanofiber substrate provides a framework that can hold the shape and size of the defect while cells grow in, and the hydrogel component promotes the growth of new blood vessels from pre-existing ones. The nanofibers provide a sufficiently strong matrix for fat stem cells to "walk" along and differentiate, a bit like making rock candy along a piece of string. The nanofibers also have a predictable and slow rate of degradation, says lead researcher Georgia Yalanis, a doctoral student who has spent the past year testing the new material. Plus the biodegradable polymers used to generate the nanofibers have a strong track record of safety; they have been widely used in many FDA-approved devices such as degradable sutures. "You don't want the material to break down too quickly, as you're not giving the body enough time to regenerate and reproduce those nice, new, healthy fat cells," Yalanis says. "While [the composite] degrades, your body's own fat grows into it. [Eventually] it will shrink with you, enlarge with you, depending on how your weight fluctuates. That is all very appealing."

Sacks and Yalanis said the team wanted to give patients the best of both worlds, the immediate replacement shape that an implant provides and the natural feel of a tissue transfer—without any of the cons. Current nondegradable implants may generate inflammation and scarring, Yalanis says, and tissue transfer is a long, invasive surgical process that essentially robs Peter
to pay Paul by taking tissue from one part of the body and planting it in another. In the rodent study, the procedure did not cause inflammation or fibrosis. Now, the team wants to conduct large-animal studies and work on an injectable model that would allow the gel to fill up a cavity and initiate fat growth in vivo. For off-the-shelf utility, the material can be poured into molds and dehydrated. Surgeons can later rehydrate the material and cut it into whatever shape is needed.

For Yalanis, the research has been personal. She chose plastic surgery as a discipline following her time at the University of Southern California's Master of Science in Global Medicine program. At USC, she researched victims of acid violence—women who had been sprayed with sulfuric or nitric acid by a husband or boyfriend as punishment for a perceived transgression. "The disfiguring is horrific," she says. "That was one reason reconstruction became interesting to me. We place high value on our physical appearance, not just beauty but small things that people take for granted. How you present yourself to the world has value. That initial presentation is something you only get to do once and greatly impacts your confidence."