Laser-Activated Nanoglues for the prevention and control of surgical site infections

摘要 在美国，每年有多达9000万例手术切口， 在外科技术、抗菌预防管理和监测方案、手术部位 感染（SSI）仍然是主要的临床挑战。SSI发生在2-5%的手术患者中， 仅在美国，每年就影响30万至50万人的生命，并与2-11倍的风险有关。 与没有SSI的患者相比，SSI给糖尿病患者带来了特别严重的挑战 以及免疫系统受损的人。SSI最常见的原因是金黄色葡萄球菌 在向CDC报告的医院中，20%的SSI和37%的社区医院中发生; 耐甲氧西林表皮葡萄金黄色葡萄球菌（MRSA）是社区医院最常见的病原体。当前临床 治疗切口和创伤性撕裂伤的实践包括缝合、粘合剂、胶带或斯台普斯， 抗菌剂掺入。然而，这些技术易受感染、伤口裂开以及 生物力学恢复差或延迟。因此，迫切需要预防和打击SSI 有效地降低患者死亡率、时间和与恢复相关的成本。在这里，我们建议 开发新型激光激活纳米胶（LANG），用于同时密封切口， 打击短期和长期或重复SSI的能力。使用LANG激光闭合切口将导致 在整个切口处进行防漏密封，从而防止微生物渗入伤口。 LANG中的银纳米棱镜（AgNP）吸收近红外（NIR）光以用于快速组织密封，并且还可以 用作抗菌活性的银源。我们实验室以前的工作表明， 纳米棒-丝LANG可以有效地用于密封小鼠的切口并抵抗细菌浸润。疗效 对于皮肤密封和MRSA感染控制，将在免疫活性， 免疫缺陷以及糖尿病和肥胖小鼠。LANG还将作为长期仓库进行调查 递送包封的抗生素，如万古霉素，这将有助于更好地抵抗长期和重复 感染易感宿主。总的来说，LANG作为一种多功能翻译工具具有巨大的翻译潜力， 在手术中有效组织凝闭和SSI控制的多面方法，并将特别适用于 免疫缺陷和糖尿病患者。

ABSTRACT Up to 90 million surgical incisions are performed every year within the United States and despite improvements in surgical techniques, administration of antimicrobial prophylaxis, and surveillance protocols, surgical site infections (SSIs) remain a major clinical challenge. SSIs occur in 2-5% of patients undergoing surgery in the United States alone, impact 300,000-500,000 lives each year, and are associated with a 2-11 times greater risk of death compared to patients without SSIs. SSIs pose particularly serious challenges to patients with diabetes and to those with compromised immune systems. The most common cause of SSI is Staphylococcus aureus which occurs in 20% of SSIs among hospitals that report to the CDC and 37% among the community hospitals; methicillin-resistant S. aureus (MRSA) is the most common pathogen in community hospitals. Current clinical practices to treat incisions and traumatic lacerations include sutures, adhesives, tape, or staples with or without antimicrobial incorporation. However, these technologies are susceptible to infection, wound dehiscence, and poor or delayed biomechanical recoveries. Thus, there exists an urgent need to prevent and combat SSIs efficiently in order to decrease patient mortality, time, and costs associated with recovery. Here, we propose the development of novel laser-activated nanoglues (LANGs) for simultaneously sealing incisions together with the ability to combat short-term and longer term or repeat SSIs. Laser sealing of incisions using LANGs will result in a leak-proof seal throughout the incision, thereby preventing the infiltration of microorganisms into the wound. Silver nanoprisms (AgNPs) in the LANGs absorb near infrared (NIR) light for rapid tissue sealing and can also serve as sources of silver for antibacterial activity. Previous work in our laboratory has indicated that gold nanorod-silk LANGs can be effectively used to seal incisions in mice and resist bacterial infiltration. The efficacy for skin sealing and MRSA infection control of LANG formulations will be evaluated in immunocompetent, immunodeficient, as well as diabetic and obese mice. LANGs will also be investigated as depots for longer-term delivery of encapsulated antibiotics like vancomycin, which will serve to better resist longer-term and repeat infections in susceptible hosts. Taken together, LANGs have tremendous translational potential as a multi- faceted approach for effective tissue sealing and SSI control in surgery, and will see particular applicability in immunodeficient and diabetic patients.