To take advantage of our body's ability to heal itself, new bio-mimicking therapeutics that could be used to treat skin wounds are being developed by UCLA researchers led by Heather Maynard, a professor of chemistry and biochemistry. Among the key players involved in natural wound-healing is a signaling molecule known as basic fibroblast growth factor (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. bFGF has been widely investigated as a tool doctors could potentially use to promote or accelerate these processes, but its instability outside the body has been a significant hurdle to its widespread use. The team has 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. The research, federally funded by the National Institutes of Health and the National Science Foundation, is published in the online edition of the journal Nature Chemistry.
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. People with diabetes, for example, can have wounds that heal very slowly. The resulting chronic wounds are debilitating and can lead to loss of limbs or even death. Yet, despite the need for wound dressings that can stimulate the body to heal wounds, very few are curative. The team 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. The advance is an important step in the use of growth factors for therapy. The ability to stabilize bFGF means that it can be potentially stored, shipped and made available for use by doctors and patients when needed any time and anywhere. This stable bFGF-polymer conjugate may also be useful in diseases other than wound healing - for example, vocal chord repair, cardiac repair and bone regeneration.