Massachusetts
General Hospital (MGH) investigators have developed a novel system for
delivery of growth factors to chronic wounds such as pressure sores and
diabetic foot ulcers. In their work published in the Jan. 18 Proceedings
of the National Academy of Sciences, the team from the MGH Center for
Engineering in Medicine (CEM) reports fabricating nanospheres containing
keratinocyte growth factor (KGF), a protein known to play an important
role in wound healing, fused with elastin-like peptides. When suspended
in a fibrin gel, these nanoparticles improved the healing of deep skin
wounds in diabetic mice.
“It
is quite amazing how just one dose of the fusion protein was enough to
induce significant tissue regeneration in two weeks” says the paper’s
lead author Piyush Koria, PhD, formerly a postdoctoral fellow at the
MGH-CEM and now at the University of South Florida. “Previous reports
have suggested that KGF can help heal chronic wounds. But in most
studies the growth factor was applied to the surface of the wound,
limiting its availability to deeper tissues and requiring repeat
applications to produce any clinical benefit. Using large quantities of
growth factor would make this therapy extremely expensive. Our work
circumvents these limitations by more efficiently delivering KFG
throughout the wound to stimulate tissue regeneration.”
The
authors describe developing a fusion protein from recombinant KGF and
elastin-like-peptides, which are major constituents of skin and other
connective tissues. Laboratory experiments showed that the fusion
protein retained the wound-healing properties of both elastin and KGF
and that it rapidly and efficiently self-assembled into nanoparticles in
response to a simple increase in temperature. When applied to deep skin
wounds in genetically diabetic mice, the nanoparticles accelerated
healing by stimulating the formation of both surface epithelial tissue
and thick fibrous connective tissue.
“This
technology has great potential because the fusion protein can be easily
manufactured at a relatively low cost, is easy to administer and does
not disappear as readily as the growth factor alone,” explains Martin
Yarmush, MD, PhD, director of the MGH Center for Engineering in Medicine
and senior author of the study. “The technology also provides a
platform for delivery of any growth factor or combination of factors.
One could imagine administering a mixture of nanoparticles, each with a
different factor, or a single set of nanoparticles with a mixture of
fusion proteins on each.”
Additional
co-authors of the report are Hiroshi Yagi, MD, PhD, and Yuko Kitagawa
MD, PhD, Keio University in Japan; and Zaki Megeed, Yaakov Nahmias, PhD,
and Robert Sheridan, MD, Massachusetts General Hospital. The study was
supported by grants from the National Institutes of Health, Shriners
Hospitals for Children, and the U.S. Department of Defense.
