Cells on the move: Blood vessel cells are shown migrating from left to right in response to injury. The red label shows the structures that cells use to move around.
Credit: Jennifer Durham
Newly-created bioactive peptides promote wound healing through the growth of new blood vessels and epithelial tissue, such as skin. These wound-healing peptides, synthesized by researchers at the Tufts Center for Innovations in Wound Healing Research, increased angiogenesis in vitroby 200 percent. Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels.
Wound repair and regeneration – Bioactive peptides derived from vascular endothelial cell extracellular matrices promote microvascular morphogenesis and wound healing in vitro
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The team from Tufts used a three-dimensional wound model to examine the effect of the bioactive peptides on wound healing. After three days, wounds treated with the peptides showed signs of robust repair, while controls did not.
Angiogenesis, the formation of new blood vessels from existing vessels, is a key step in all types of wound healing from knee scrapes to venous stasis ulcers, pressure sores and diabetic foot ulcers. In order for tissues to be repaired, there must be an adequate blood supply bringing nutrients, oxygen, and signaling molecules to the site of the injury. Collageneses are enzymes that remodel extracellular matrix by cleaving one of its key components, collagen.
“The most potent wound-healing peptide is a ‘combinatorial’ peptide synthesized from bioactive fragments derived from the collagenase treatment of biosynthesized matrix. Outcomes of these studies suggest that it could be possible to create personalized regenerative medicine-based wound healing therapies and platforms that would be tailored to individuals. We are currently testing the efficacy of these fragments in an effort to develop better treatments for wound healing. Formulation of the bioactive peptides into heat-stable and portable materials could be of extreme value to soldiers injured in combat,” said Herman.
Herman says that the team has since had promising results testing the agents in animal models, and he hopes to move the technology toward human trials. He envisions that the peptides could be sprinkled over wounds as dry particles or suspended in a gel.
Studies in our laboratory indicate that collagenase from Clostridium histolyticum promotes endothelial cell and keratinocyte responses to injury in vitro and wound healing in vivo. We postulate that matrix degradation by Clostridial collagenase creates bioactive fragments that can stimulate cellular responses to injury and angiogenesis. To test this hypothesis, we performed limited digestion of defined capillary-endothelial-derived extracellular matrices using purified human or bacterial collagenases. Immunoprecipitation with antibodies recognizing collagens I, II, III, IV, and V, followed by mass spectrometry reveals the presence of unique fragments in bacterial, but not human-enzyme-digested matrix. Results show that there are several bioactive peptides liberated from Clostridial collagenase-treated matrices, which facilitate endothelial responses to injury, and accelerate microvascular remodeling in vitro. Fragments of collagen IV, fibrillin-1, tenascin X, and a novel peptide created by combining specific amino acids contained within fibrillin 1 and tenascin X each have profound proangiogenic properties. The peptides used at 10-100 nM increase rates of microvascular endothelial cell proliferation by up to 47% and in vitro angiogenesis by 200% when compared with serum-stimulated controls. Current studies are aimed at revealing the molecular mechanisms regulating peptide-induced wound healing while extending these in vitro observations using animal modeling.
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