Early Metazoan Nano-collagens for Promotion of Wound Healing

早期后生动物纳米胶原蛋白促进伤口愈合

基本信息

批准号：
8212104
负责人：
ANGEL ANNE YANAGIHARA
金额：
$ 30.08万
依托单位：
UNIVERSITY OF HAWAII AT MANOA
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-01-10 至 2014-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8212104
关键词：
Accidental Injury Acute Address Anemone Animal Model Binding Biochemistry Biocompatible Materials Biological Assay Biophysics Blood Circulation Blood Platelets Carybdea Cells Cellular Immunology Chymase Cicatrix Cnidaria Collagen Collagen Receptors Cubozoa Cutaneous Cysteine Data Decubitus ulcer Deposition Dermal Development Eicosanoids Employee Strikes Engineering Exhibits Eye Fibrin Fibroblasts Future Glutamine Glycine Grant Growth Factor Hawaiian population Healed Histology Human Immune response Immunologist In Vitro Incubated Inflammatory Inflammatory Response Integrins Jellyfish Lesion Life Mast Cell Stabilizer Mechanics Mediator of activation protein Medical Device Modality Modeling Molecular Molecular Analysis Mus NMR Spectroscopy Operative Surgical Procedures Organelles Peptide Hydrolases Peptides Phosphotransferases Positioning Attribute Post-Translational Protein Processing Preparation Proline Property Proteins Recovery Relative (related person)Research Resolution Sea Anemones Signal Transduction Speed Steel Sting Injury Structure Structure-Activity Relationship Tensile Strength Testing Therapeutic Time Tissues Toxin Translating Tryptase Ursidae Family Vascularization Vertebrates Wound Healing base capsule chemokine coral cytokine healing hemodynamics immunogenicity improved in vitro Assay in vivo innovation insight mast cell medical implant molecular dynamics molecular scale nano nanomaterials nanometer novel point of care pressure public health relevance receptor research study response scale up solid state nuclear magnetic resonance therapeutic development wound

项目摘要

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.

描述（由申请人提供）：珊瑚，海葵和水母的刺痛仪（线虫囊）表现出显着的生物物理特性，使得在子弹样力量和快速的猎物中出现了猎物诱发小管的排放。线虫胶囊壁和小管由高度专业的蛋白质组成，为其提供有限的信息。我们最近发现，夏威夷盒子水母的一种新颖的，自组装的“纳米胶原蛋白”，Carybdea alata通过血小板引起大规模的纤维蛋白沉积并激活肥大细胞信号传导，这表明了驱动伤口愈合的两个关键方面的显着潜力。拟议研究的总体目标是基于这种有效的生物活性的新型肽开发新的伤口修复剂，并表现出自组装纳米材料的属性。中心的前提是，稳健的纤维纤维蛋白促促炎活性是必要的，足以充当有用的第一反应伤口管理和伤口治疗剂。由多个PI组成的跨学科团队，包括毒素生物化学家，免疫学家和蛋白质生物物理学家，已组装，以解决治疗潜力的关键方面。我们的建议旨在解决这一独特生物材料治疗发展之前的两个关键问题。首先，我们将表征该纳米 - 胶原蛋白的生物物理和材料特性。该目标的完成将使我们能够检查制造和交付方式。其次，我们将评估并优化这种新型胶原蛋白对局部免疫反应的有益和改善促进的潜力。该目标的完成将使我们了解该材料在伤口中应用的免疫学后果。在赠款期间结束时，我们将定位，可以翻译我们使用古老的早期后生动物自我组装胶原蛋白来治愈人类伤口的范式转移方法。拟议的研究具有创新性，因为基于天然纳米 - 胶原蛋白的有效纳米材料具有很高的潜力，以促进伤口管理并加速人类的伤口愈合。这种改善的应用的可用性将对严重威胁生命的皮肤伤口的护理点反应产生直接影响，这是由于急性意外伤害或皮肤病变量（例如dep毛溃疡）导致的循环受损。公共卫生相关性：夏威夷盒子水母刺胶原胶原具有非凡的生物物理特性，可与外科钢相抗衡。发现具有自组装和血小板纤维纤维蛋白生成特性的非常健壮的“纳米 - 胶原蛋白”（〜10纳米）肽可为伤口愈合中的纳米材料应用，以及作为组织，医疗器械和植入物工程的生物材料。