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

基本信息

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
项目类别：
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

项目摘要

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.

抽象的尽管有所改进，美国每年仍进行多达 9000 万次手术切口手术技术、抗菌药物预防和监测方案、手术部位感染（SSI）仍然是一个重大的临床挑战。在接受手术的患者中，有 2-5% 发生 SSI 仅在美国，每年就会影响 300,000-500,000 人的生命，风险增加 2-11 倍与没有 SSI 的患者相比，死亡率更高。 SSI 给糖尿病患者带来了特别严峻的挑战以及那些免疫系统受损的人。 SSI 最常见的原因是金黄色葡萄球菌在向 CDC 报告的医院中，有 20% 的 SSI 发生这种情况，在社区医院中，这一比例为 37%；耐甲氧西林金黄色葡萄球菌（MRSA）是社区医院最常见的病原体。目前临床治疗切口和创伤性撕裂伤的做法包括缝线、粘合剂、胶带或钉书钉，有或没有抗菌剂的掺入。然而，这些技术容易受到感染、伤口裂开和生物力学恢复不良或延迟。因此，迫切需要预防和打击 SSI 有效地降低患者死亡率、时间和与康复相关的成本。在此，我们建议开发新型激光激活纳米胶（LANG），用于同时密封切口和对抗短期和长期或重复 SSI 的能力。使用 LANG 激光密封切口将导致整个切口的防漏密封，从而防止微生物渗入伤口。 LANG 中的银纳米棱柱 (AgNP) 吸收近红外 (NIR) 光以实现快速组织密封，并且还可以作为抗菌活性银的来源。我们实验室之前的工作表明，金纳米棒-丝 LANG 可有效用于密封小鼠切口并抵抗细菌渗透。功效用于皮肤密封和 MRSA 感染控制的 LANG 制剂将在免疫活性方面进行评估，免疫缺陷小鼠，以及糖尿病小鼠和肥胖小鼠。 LANG 也将作为长期仓库进行调查提供万古霉素等封装抗生素，这将有助于更好地抵抗长期和重复易感宿主的感染。总而言之，LANG 作为一种多用途技术具有巨大的转化潜力。多面方法可在手术中实现有效的组织密封和 SSI 控制，并将特别适用于免疫缺陷和糖尿病患者。