Bioengineered Skin Sealants

摘要 在创伤和大多数情况下，软组织的有效接近、修复和愈合是一个巨大的挑战 需要快速、液体密封的真皮组织，这有助于快速恢复组织的生物力学性能 并能抵抗感染。缝合和钉子是常用的，但不能立即封闭，原因是 严重的组织创伤，容易感染，留下特有的疤痕和/或美容不良， 尤其是在可见区域。胶，包括氰基丙烯酸酯和纤维蛋白，通常会导致较差的生物力学性能 恢复，可能会很麻烦，和/或遭受配方依赖毒性，这限制了他们的 仅适用于人类的表面使用。使用非电离光的激光激活纳米胶体(LNG)， 与组织结合以快速提供不透气密封，导致软组织更好的生物力学恢复， 并证明更好的美容效果是皮肤封闭和修复的有吸引力的选择。药效 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 染料(例如吲哚青绿)将被用于封闭活体动物的全层伤口。 将进行生物力学和生化表征，以研究其疗效和 硅胶与缝线和普通胶粘剂的生物相容性比较 还将研究将其作为提高疗效的组合方法。在恢复的早期阶段，密封的 组织很脆弱，愈合缓慢可能会导致并发症，包括手术部位感染。小分子 蛋白质疗法将与朗格雷配合使用，以加速皮肤的闭合和修复 伤口，尤其是早期的伤口。Lang密封和其他近似方法的有效性(例如 将使用伤口部位的高光谱和光声成像进行可视化，并且 组织应变的异质性，通过数字图像相关性可视化，将作为一种指标进行调查 可能会留下疤痕。因此，将使用一种 结合成像、生物力学和生化分析。伤口感染影响多达500,000人的生命 每年，与未感染的患者相比，死亡风险更大。朗格将会成为 用抗菌药物配制，以便同时封闭伤口，加速修复和 对抗耐甲氧西林金黄色葡萄球菌(MRSA)，这是社区医院最常见的病原体。 我们的研究将导致新的多功能语言，显示出高效的密封，递送 用于加速缝合和早期修复以及对抗感染的药物。我们预计朗格将成为 尤其是在需要快速皮肤密封和加速修复的应用中，缝合和修复 钉子的疗效有限，感染控制很关键，和/或需要改进美容 性能。

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.