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

激光激活纳米胶用于预防和控制手术部位感染

• 批准号: 10249234
• 负责人: Kaushal Rege
• 金额: $ 22.57万
• 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: 2020-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10249234
• 关键词: Address; Adhesions; Adhesives; Animals; Anti-Bacterial Agents; Antibiotics; Back; Biochemical; Biological Assay; Biomechanics; Centers for Disease Control and Prevention (U.S.); Clinical; Collagen; Colony-forming units; Community Hospitals; Dermal; Development; Diabetes Mellitus; Diabetic mouse; Encapsulated; Enzyme-Linked Immunosorbent Assay; Evaluation; Fibroins; Formulation; Glues; Goals; Gold; Histology; Hospitals; Image; Immune system; Immunocompetent; Immunocompromised Host; Immunohistochemistry; Inbred BALB C Mice; Infection; Infection Control; Infection prevention; Infiltration; Inflammation; Ions; Laboratories; Laceration; Lasers; Lead; Light; Methods; Mouse Strains; Mus; Nature; Obese Mice; Obesity; Operative Surgical Procedures; Pathology; Patient-Focused Outcomes; Patients; Prevention; Property; Prophylactic treatment; Protocols documentation; Recovery; Reporting; Research; Silk; Silver; Site; Skin; Source; Spine surgery; Staphylococcus aureus; Staphylococcus aureus infection; Surgical Wound Infection; Surgical incisions; Surgical sutures; Techniques; Technology; Tensile Strength; Thick; Time; Tissues; United States; Vancomycin; Work; Wound models; absorption; angiogenesis; antimicrobial; biomaterial compatibility; chronic wound; clinical practice; clinical translation; clinically relevant; combat; cost; cytokine; db/db mouse; diabetic; diabetic patient; fluorescence imaging; healing; high risk; improved; improved outcome; in vitro Assay; innovation; mechanical properties; methicillin resistant Staphylococcus aureus; microorganism; mortality; mortality risk; nanoGold; nanomaterials; nanorod; novel; novel strategies; pathogen; preclinical efficacy; prevent; prophylactic; repaired; response; seal; soft tissue; wound; wound closure

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.

抽象的 每年在美国，每年进行多达9000万辆手术切口，尽管有所改善 在手术技术中，抗菌预防和监视方案的给药，手术部位 感染（SSIS）仍然是主要的临床挑战。 SSI发生在2-5％的接受手术的患者中 仅美国，每年影响300,000-500,000寿命，与风险大2-11倍 与没有SSI的患者相比，死亡。 SSIS对糖尿病患者构成特别严重的挑战 以及那些免疫系统受损的人。 SSI的最常见原因是金黄色葡萄球菌 在向疾病预防控制中心报告的医院中，有20％的SSI发生在社区医院中的37％； 耐甲氧西林金黄色葡萄球菌（MRSA）是社区医院中最常见的病原体。当前的临床 治疗切口和创伤性裂伤的实践包括缝合线，胶粘剂，胶带或钉书钉 抗菌素掺入。但是，这些技术容易感染，伤口开发和 生物力学回收率差或延迟。因此，迫切需要预防和战斗SSI 有效地为了减少患者死亡率，时间和与康复相关的成本。在这里，我们建议 开发新型激光激活的纳米lues（Langs），以同时密封切口与 能够对抗短期和长期或重复SSI的能力。使用langs对切口的激光密封将导致 整个切口中有防泄漏的密封，从而防止了微生物渗入伤口。 Langs中的银色纳米二氧化（AGNP）吸收在红外线（NIR）光（NIR）的快速组织密封，也可以 用作抗菌活性的银来源。我们实验室的先前工作表明黄金 可以有效地使用纳米轨道 - silk langs来密封小鼠的切口并抵抗细菌浸润。功效 对于皮肤密封和MRSA感染控制，将在免疫能力中评估 免疫缺陷，糖尿病和肥胖小鼠。 Langs也将作为长期的仓库进行研究 递送封装的抗生素（如万古霉素）将更好地抵抗长期和重复 易感宿主的感染。综上所述，Langs具有巨大的翻译潜力 在手术中进行有效组织密封和SSI控制的刻面方法，并将在 免疫缺陷和糖尿病患者。