Bioengineered Skin Sealants

生物工程皮肤密封剂

• 批准号: 10457977
• 负责人: Kaushal Rege
• 金额: $ 37.69万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10457977
• 关键词: Affect; Agonist; Animals; Anti-Bacterial Agents; Area; Binding; Biochemical; Biological; Biological Assay; Biomechanics; Biomedical Engineering; Biopsy; Characteristics; Cicatrix; Clinical; Colony-forming units; Community Hospitals; Consumption; Correlation Studies; Cyanoacrylates; Dermabond; Dermal; Drug Delivery Systems; Drug or chemical Tissue Distribution; Drug usage; Dyes; Evaluation; Excision; Fibrin; Formulation; Glues; Gold; Heterogeneity; Histamine Receptor; Histology; Histopathology; Human; Image; Immunocompetent; Immunohistochemistry; In Vitro; Inbred BALB C Mice; Indocyanine Green; Infection; Infection Control; Investigation; Investigational Therapies; Laceration; Lasers; Lead; Lesion; Light; Liquid substance; Maps; Mediator of activation protein; Methods; Nylons; Operative Surgical Procedures; Patients; Performance; Pharmaceutical Preparations; Play; Prevention; Property; Proteins; Recovery; Research; Role; SCID Mice; Serpins; Silk; Site; Skin; Skin Tissue; Skin graft; Skin repair; Spine surgery; Staphylococcus aureus infection; Surgical Wound Infection; Surgical incisions; Surgical sutures; Tensile Strength; Thick; Time; Tissues; Toxic effect; Translating; Trauma; Traumatic injury; Vancomycin; Visualization; Water; Wound Infection; biomaterial compatibility; chronic wound; combat; digital imaging; healing; immunoregulation; improved; in vivo evaluation; infrared microscopy; methicillin resistant Staphylococcus aureus; mortality risk; mouse model; nanoparticle; nanorod; novel; novel strategies; pathogen; photoacoustic imaging; porcine model; repaired; seal; sealant; skin wound; small molecule; soft tissue; therapeutic protein; tissue repair; tissue trauma; trauma surgery; ultrasound; wound

Abstract Effective approximation, repair, and healing of soft tissues is a significant challenge in trauma and most cases require rapid, liquid-tight sealing of dermal tissue, which aids fast recovery of tissue biomechanical properties and resists infections. Sutures and staples are commonly used but do not lead to immediate sealing, cause significant tissue trauma, are prone to infection, leave characteristic scars and / or suffer from poor cosmesis, especially in visible areas. Glues, including cyanoacrylate and fibrin, typically result in poor biomechanical recoveries, can be cumbersome to apply, and / or suffer from formulation-dependent toxicities, which limits their application only to superficial use in humans. Laser-activated nanoglues (LANGs) that use non-ionizing light, integrate with tissue to rapidly provide a flight-tight seal, result in better biomechanical recoveries of soft tissues, and demonstrate better cosmesis profiles are attractive alternatives for dermal sealing and repair. The efficacy of LANGs, formulated using silk protein and near infrared light-absorbing nanoparticles (e.g. gold nanorods) or dyes (e.g. indocyanine green), will be investigated for sealing full thickness wounds in live animals. Biomechanical and biochemical characterization will be carried out in order to investigate the efficacy and biocompatibility of LANGs compared to sutures and conventional glues; a combination of LANGs with sutures will also be investigated as a combination approach for enhanced efficacy. In early stages of recovery, sealed tissue is vulnerable and slow healing can lead to complications including surgical-site infections. Small-molecule and protein therapeutics will be formulated with LANGs in order to accelerate closure and repair of dermal incisional wounds particularly at earlier times. Efficacy of LANG sealing and other approximation methods (e.g. sutures) will be visualized using hyperspectral and photoacoustic imaging of the wound site, and the heterogeneity of tissue strain, visualized using digital image correlation, will be investigated as an indicator of potential scarring. A comprehensive picture of LANG-facilitated tissue sealing will thus be generated using a combination of imaging, biomechanical, and biochemical analyses. Wound infections affect up to 500,000 lives each year, and are associated with a greater risk of death compared to patients without infection. LANGs will be formulated with antibacterial drugs in order to simultaneously seal wounds, engender accelerated repair and combat methicillin-resistant S. aureus (MRSA), which is the most common pathogen in community hospitals. Our research will lead to novel, multifunctional LANGs that demonstrate high efficacy for sealing, delivery of drugs for accelerating closure and early-stage repair, and combat infections. We anticipate that LANGs will be translated particularly in applications where rapid dermal sealing and accelerated repair are desired, sutures and staples have limited efficacy, infection control is critical and / or where there is a need for improved cosmesis performance.

摘要 软组织的有效缝合、修复和愈合是创伤和大多数病例中的重大挑战， 这有助于快速恢复组织的生物力学特性 并且抵抗感染。通常使用缝线和斯台普斯，但不能立即闭合，原因是 显著组织创伤、易于感染、留下特征性疤痕和/或遭受不良美容， 尤其是在可见区域。胶水，包括氰基丙烯酸酯和纤维蛋白，通常会导致生物力学性能差， 回收，可能是繁琐的应用，和/或遭受制剂依赖性毒性，这限制了它们的应用。 仅用于人类的表面应用。使用非电离光的激光激活纳米胶（LANG）， 与组织结合以快速提供飞行密封，导致软组织更好生物力学恢复， 并证明更好的美容外形是皮肤密封和修复的有吸引力的替代方案。疗效 使用丝蛋白和近红外光吸收纳米颗粒（例如金纳米棒）配制的LANG，或 将研究染料（例如吲哚菁绿色）用于密封活动物的全层伤口。 将进行生物力学和生物化学表征，以研究疗效和 LANG与缝线和传统胶水相比的生物相容性; LANG与缝线的组合 还将作为增强功效的组合方法进行研究。在恢复的早期阶段， 组织是脆弱的，并且缓慢的愈合可导致并发症，包括器官部位感染。小分子 和蛋白质治疗剂将与LANG一起配制，以加速真皮的闭合和修复。 尤其是早期的伤口。LANG凝闭和其他缝合方法（例如， 缝线）将使用伤口部位的高光谱和光声成像进行可视化， 将研究使用数字图像相关性可视化的组织应变的异质性，作为 可能留下疤痕因此，将使用LANG生成LANG促进的组织凝闭的全面图片， 成像、生物力学和生化分析的组合。伤口感染影响多达50万人的生命 与未感染的患者相比，这些患者的死亡风险更高。LANG将是 与抗菌药物一起配制，以便同时密封伤口，产生加速修复， 对抗耐甲氧西林S.金黄色葡萄球菌（MRSA），这是社区医院最常见的病原体。 我们的研究将导致新型的多功能LANG，其在密封、递送 加速闭合和早期修复的药物，以及对抗感染。我们预计，LANG将 特别是在需要快速皮肤密封和加速修复的应用中， 斯台普斯的有效性有限，感染控制至关重要和/或需要改善外观 性能