Early Metazoan Nano-collagens for Promotion of Wound Healing

说明（由申请人提供）：珊瑚、海葵和水母（刺胞动物门）的刺细胞器（刺胞）具有显著的生物物理特性，因此，以子弹般的力量和速度释放猎物刺穿小管。包囊囊壁和小管由高度特化的蛋白质组成，其信息有限。我们最近发现，来自夏威夷箱形水母Carybdea阿拉塔的新型自组装“纳米胶原蛋白”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，这表明驱动伤口愈合的两个关键方面的显著潜力。 拟议研究的总体目标是基于这种新型肽开发新的伤口修复剂，这种新型肽具有潜在的生物活性，并具有自组装纳米材料的属性。中心前提是，强大的纤维蛋白原促炎症活性对于作为有用的第一反应伤口管理和伤口愈合剂是必要且足够的。一个由多个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制药学家，已经组装起来，以解决治疗潜力的关键方面。我们的建议旨在解决这种独特的生物材料的治疗发展之前的两个关键问题。首先，我们将描述这种纳米胶原蛋白的生物物理和材料特性。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性促进潜力。这一目标的完成将使我们能够了解将该材料应用于伤口的免疫学后果。在资助期结束时，我们将致力于转化我们的范式转变方法，即使用古老的早期后生动物自组装胶原蛋白来治愈人类伤口。拟议的研究是创新的，因为开发基于天然纳米胶原蛋白的有效纳米材料的潜力很大，可以促进伤口管理和加速人类伤口愈合。这种改进的应用的可用性将对对严重危及生命的皮肤伤口的护理点响应产生直接影响，这些伤口由急性意外伤害或皮肤损伤（例如褥疮性溃疡）引起，来自受损的循环。 公共卫生相关性：夏威夷箱形水母刺细胞胶原蛋白具有非凡的生物物理特性，其抗拉强度可与外科手术用钢相媲美。具有自组装和血小板纤维蛋白原特性的非常稳健的“纳米胶原”（~10纳米）肽的发现提供了在伤口愈合中的可能的纳米材料应用以及作为用于组织、医疗装置和植入物工程的生物材料。

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.