Early Metazoan Nano-collagens for Promotion of Wound Healing

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): The stinging-cell apparatus (nematocyst) of corals, anemone and jellyfish (Phylum Cnidaria) exhibits remarkable biophysical properties such that the discharge of the prey-piercing tubule occurs at bullet-like forces and speed. The nematocyst capsule wall and tubule are composed of highly specialized proteins, for which limited information is available. We have recently discovered that a novel, self-assembling, "nano- collagen", from the Hawaiian box jellyfish, Carybdea alata causes massive fibrin deposition by platelets and activates mast cell signaling, suggesting a remarkable potential to drive two key aspects of wound healing. The overall objective of the proposed research is to develop new wound-repair agents based on this novel peptide that is potently bioactive and exhibits attributes of a self-assembling nanomaterial. The central premise is that the robust fibrinogenic pro-inflammatory activity is necessary and sufficient to serve as a useful first- response wound-management and wound-healing agent. An interdisciplinary team of multiple PIs, comprising a toxin biochemist, an immunologist and a protein biophysicist, has been assembled to address key aspects of the therapeutic potential. Our proposal seeks to address two critical questions that precede therapeutic development of this unique biomaterial. First, we will characterize the biophysical and materials properties of this nano-collagen. Completion of this objective will position us to examine fabrication and delivery modalities. Second, we will evaluate and optimize the potential for beneficial and ameliorative promotion of local immune responses by this novel collagen. Completion of this objective will position us to understand the immunological consequences of the application of this material to wounds. At the conclusion of the grant period, we will be positioned to translate our paradigm-shifting approach of using an ancient early metazoan self-assembling collagen to heal wounds in humans. The proposed research is innovative because of the high potential of developing potent nanomaterials, based on a natural nano-collagen, to promote wound management and accelerate wound healing in humans. The availability of such improved applications would have an immediate impact on point-of-care response to severe life-threatening dermal wounds, resulting from acute accidental injuries or cutaneous lesions, such as decubitus ulcers, from compromised circulation. PUBLIC HEALTH RELEVANCE: Hawaiian box jellyfish stinging-cell collagens exhibit extraordinary biophysical properties that rival surgical steel in tensile strength. Discovery of a remarkably robust "nano-collagen" (~10 nanometer) peptide with self-assembling and platelet fibrinogenic properties provides for possible nanomaterial applications in wound healing and as a biomaterial for tissue, medical device and implant engineering.