A team of plastic surgeons and material scientists has made an important advance in treating the common clinical problem of soft tissue loss. They have invented a synthetic soft tissue substitute that is well tolerated and encourages the growth of soft tissue and blood vessels. This new material retains its shape without being too dense; overcoming challenges with current tissue fillers that tend to be either too soft or not porous enough to let cells move in and start regrowing tissue.
Common clinical problem
A report on this work appears today in Science Translational Medicine. “As a plastic surgeon; I see patients every day who lose soft tissue like skin, fat and muscle from cancer surgery; trauma or other conditions. Currently our options are limited to implants; which are plagued by fibrosis and other problems; or ‘borrowing’ tissues from elsewhere in the body; which can cause deformity there as well;” says Sashank Reddy, M.D., Ph.D., an instructor in plastic and reconstructive surgery at the Johns Hopkins University School of Medicine and the medical director for Johns Hopkins Technology Ventures.
“Nature abhors a vacuum, and soft tissue defects can contract; deform and fill in with scar. In order to reconstruct these defects, we often move fat from one part of the body to another with a process called fat grafting. This is not always successful; as typically half of the grafted fat will die after it’s transplanted; and it’s often hard to predict how well these procedures will work out;” says Justin Sacks, M.D., M.B.A., vice chair of clinical operations and an associate professor of plastic and reconstructive surgery at the Johns Hopkins University School of Medicine.
Several years ago; Reddy and Sacks approached Hai-Quan Mao about developing a material that could allow them to do fewer invasive surgeries to replace lost soft tissue. They wanted to find a better way to help patients while avoiding some of the risks of surgery.
“This was an interesting problem to tackle from an engineering point of view;” says Hai-Quan Mao, Ph.D., a professor of materials science and engineering at the Whiting School ; of Engineering and biomedical engineering at the Johns Hopkins University School of Medicine and the associate director of the Institute for Nano Bio Technology at Johns Hopkins.
“Typically a gel-like material that’s porous enough for cells to spread inside is too soft to be able to hold its shape; and a material that is able to retain its shape when placed ; in the soft tissue defects is conversely too dense for cells to grow into. We really needed to synthesize a new material that is soft and porous yet resilient almost like fat tissue or Jell-O.”
Since fat often is used to fill in space during reconstructive surgery procedures; the team started by examining the structure and physical properties of fat. They used real human fat as well as animal fat and measured everything about it how elastic it is; how viscous and how bouncy. They also examined its microscopic structure; which consists of large cells clustered around a fibrous matrix the extracellular matrix that lends shape and stability to fat tissue.
Once they had those measurements, they started experimenting. They reasoned that the material needed to be safe and well tolerated; so they started with a so-called hydrogel made of hyaluronic acid; a naturally occurring component of the body’s extracellular matrix. Further; hyaluronic acid is already used in more than 90% of commercial cosmetic dermal fillers in the United States.
But the hydrogel alone cannot retain its shape while retaining porosity, says Mao; rather it will be deformed too easily at the site of repair in the body. So they added another material to the hydrogel to help give it some stiffness. The research team turned to polycaprolactone (PCL) fibers, the same material used in some resorbable stitches.