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

• 批准号: 8607898
• 负责人: ANGEL ANNE YANAGIHARA
• 金额: $ 29.67万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-10 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8607898
• 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; biophysical properties; 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

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.

描述（由申请人提供）：珊瑚、海葵和水母（刺胞门）的刺细胞器官（刺丝囊）表现出显著的生物物理特性，例如刺穿猎物的小管以子弹般的力量和速度放电。刺丝囊囊囊壁和小管是由高度特化的蛋白质组成的，关于这方面的信息有限。我们最近从夏威夷箱形水母（Carybdea alata）中发现了一种新颖的、自组装的“纳米胶原蛋白”，它可以通过血小板引起大量纤维蛋白沉积，并激活肥大细胞信号传导，这表明它在推动伤口愈合的两个关键方面具有显著的潜力。该研究的总体目标是开发基于这种新型肽的新型伤口修复剂，这种新型肽具有强大的生物活性，并具有自组装纳米材料的特性。中心前提是强大的纤维蛋白原促炎活性是必要和充分的，可以作为有用的第一反应伤口管理和伤口愈合剂。一个由多名pi组成的跨学科团队，包括一名毒素生物化学家、一名免疫学家和一名蛋白质生物物理学家，已经组建起来，以解决治疗潜力的关键方面。我们的建议旨在解决在这种独特生物材料的治疗发展之前的两个关键问题。首先，我们将表征这种纳米胶原蛋白的生物物理特性和材料特性。完成这一目标将使我们能够检查制造和交付方式。其次，我们将评估和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。完成这一目标将使我们能够了解将这种材料应用于伤口的免疫学后果。在资助期结束时，我们将定位于转化我们的范式转换方法，使用古老的早期后生动物自组装胶原蛋白来治愈人类的伤口。这项拟议的研究具有创新性，因为基于天然纳米胶原蛋白开发有效的纳米材料具有很高的潜力，可以促进人体伤口管理和加速伤口愈合。这种改进的应用程序的可用性将对护理点对严重危及生命的皮肤伤口的反应产生直接影响，这些伤口是由急性意外伤害或皮肤损伤引起的，例如由循环受损引起的褥疮。

项目成果

Phylogenetic analysis of higher-level relationships within Hydroidolina (Cnidaria: Hydrozoa) using mitochondrial genome data and insight into their mitochondrial transcription.

使用线粒体基因组数据以及对线粒体转录的洞察力，对氢化烷（Cnidaria：hydrozoa）内高级关系的系统发育分析。

• DOI: 10.7717/peerj.1403
• 发表时间: 2015
• 期刊: PeerJ
• 影响因子: 2.7
• 作者: Kayal E;Bentlage B;Cartwright P;Yanagihara AA;Lindsay DJ;Hopcroft RR;Collins AG
• 通讯作者: Collins AG