Whether it is a small nick or large surgical incision, healing is dependent upon the body’s ability to heal itself. A vital role is played by our own natural biomolecules in the healing process, including their contribution to the growth of new cells and the development of new blood vessels that provide nutrients to those cells. UCLA scientists are developing new therapeutics that could accelerate the wound healing process. The research could lead to new treatments that could promote healing in individuals with problems in that area, such as diabetics. They published their findings online on February 17 in the journal Nature Chemistry; the new study will also appear in an upcoming print edition of the
A research team led by Heather Maynard, a professor of chemistry and biochemistry and a member of UCLA’s California NanoSystems Institute, are working to take advantage of our body’s ability to heal itself by developing new bio-mimicking therapeutics that could be used to treat skin wounds. A key component of natural wound-healing is a signaling molecule known as basic fibroblast growth factor, or bFGF, which is secreted by our cells to trigger processes that are involved in healing, as well as embryonic development, tissue regeneration, bone regeneration, the development and maintenance of the nervous system, and stem cell renewal. Dr. Maynard note that bFGF has been widely investigated as a tool doctors could potentially use to promote or accelerate these processes; however, its instability outside the body has been a significant hurdle to its widespread use.
Now, the researchers have discovered how to stabilize bFGF based on the principle of mimicry. Relying on the growth factor’s ability to bind heparin (a naturally occurring complex sugar found on the surface of our cells) the team synthesized a polymer that mimics the structure of heparin. When attached to bFGF, the new polymer makes the protein stable to the many stresses that normally inactivate it, rendering it a more suitable candidate for medical applications.
Our ability to heal from wounds is essential to our survival. When those natural healing processes are compromised, serious wounds can lead to infection and other health problems. For example, individuals with diabetes often experience slow wound healing. The resulting chronic wounds are debilitating and can lead to loss of limbs or even death. However, despite the need for wound dressings that can stimulate the body to heal wounds, very few are curative. “This very important clinical need is the motivation behind our research,” explained, Dr. Maynard.
The importance of fibroblast growth factor was recognized in 1973, when biologist Hugo Armelin discovered that this previously unknown chemical, extracted from the pituitary gland, successfully caused cells to divide. Since then, researchers have applied fibroblast growth factor to wounds such as foot ulcers resulting from diabetes; however, to date, the treatments have not been very effective. Dr. Maynard noted that scientists now recognize that these growth factors typically lose their activity quickly in storage.
Knowing that other key biomolecules have been stabilized before with the help of polymers, the researchers developed a strategy to maintain bFGF activity by taking advantage of its known structure and binding capabilities. Their new polymer, p(SS-co-PEGMA), mimics heparin’s natural ability to stabilize the growth factor.
After showing that p(SS-co-PEGMA) was non-toxic to human cells important in wound healing, they used it to conjugate bFGF and demonstrated that they could keep the growth factor active outside of the body for extended periods of time, even after it is exposed to heat, cold, enzymes that would normally break it down, and acidic conditions like those found in the wound injury setting. Moreover, they showed that this bound bFGF functions just like normal bFGF to trigger the same signaling pathways involved in the healing process.