Urie Russell, McBride Michelle, Ghosh Deepanjan, Fattahi Ali, Nitiyanandan Rajeshwar, Popovich John, Heys Jeffrey J, Kilbourne Jacquelyn, Haydel Shelley E, Rege Kaushal
Chemical Engineering Program, School for Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ 85287, USA.
Biodesign Institute Center for Bioelectronics and Biosensors, Arizona State University, Tempe, AZ 85287, USA.
Biomater Sci. 2021 May 18;9(10):3791-3803. doi: 10.1039/d0bm01438a.
Surgical-site infections (SSIs) occur in 2-5% of patients undergoing surgery in the US alone, impacting 300 000-500 000 lives each year, and presenting up to 11 times greater risk of death compared to patients without SSIs. The most common cause of SSI is Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA) is the most common pathogen in community hospitals. Current clinical devices used for approximating incisions and traumatic lacerations include sutures, adhesives, tapes, or staples with or without antimicrobial incorporation. However, current closure technologies may not provide adequate protection against infection, are susceptible to wound dehiscence, and can result in delayed biomechanical recoveries. Laser-activated tissue repair is a sutureless technique in which chromophore-loaded sealants convert laser light energy to heat in order to induce rapid tissue sealing. Here, we describe the generation and evaluation of laser-activated sealant (LASE) biomaterials, in which, indocyanine green (ICG), an FDA-approved dye, was embedded in a silk fibroin matrix and cast into films as wound sealants. Silk-ICG films were subjected to different near-infrared (NIR) laser powers to identify temperatures optimal for laser sealing of soft tissues. A mathematical model was developed in order to determine the photothermal conversion efficiency of LASEs following laser irradiation. NIR laser activation of silk-ICG LASEs increased the recovery of skin biomechanical strength compared to sutured skin in full-thickness incisional wounds in immunocompetent mice, and live animal imaging indicated persistence of silk-ICG LASEs over several days. LASEs loaded with the antibiotic vancomycin demonstrated higher efficacies for combating MRSA infections in a mouse model of surgical site infection compared to antibacterial sutures. Our results demonstrate that LASEs can be loaded with antimicrobial drugs and may serve as new multifunctional biomaterials for rapid tissue sealing, repair and surgical site protection following surgery.
仅在美国，接受手术的患者中有2%至5%会发生手术部位感染（SSI），每年影响30万至50万人的生命，与未发生SSI的患者相比，死亡风险高出11倍。SSI最常见的原因是金黄色葡萄球菌，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。目前用于缝合切口和创伤性撕裂伤的临床器械包括带有或不带有抗菌成分的缝线、粘合剂、胶带或吻合钉。然而，目前的闭合技术可能无法提供足够的抗感染保护，易发生伤口裂开，并可能导致生物力学恢复延迟。激光激活组织修复是一种无需缝合的技术，其中负载发色团的密封剂将激光光能转化为热能，以诱导组织快速密封。在此，我们描述了激光激活密封剂（LASE）生物材料的制备和评估，其中，FDA批准的染料吲哚菁绿（ICG）被嵌入丝素蛋白基质中，并制成薄膜作为伤口密封剂。对丝-ICG薄膜施加不同的近红外（NIR）激光功率，以确定软组织激光密封的最佳温度。建立了一个数学模型来确定激光照射后LASE的光热转换效率。在免疫功能正常的小鼠全层切口伤口中，与缝合皮肤相比，NIR激光激活的丝-ICG LASE提高了皮肤生物力学强度的恢复，活体动物成像表明丝-ICG LASE在数天内持续存在。与抗菌缝线相比，负载抗生素万古霉素的LASE在手术部位感染小鼠模型中对抗MRSA感染的效果更高。我们的结果表明，LASE可以负载抗菌药物，并可作为新型多功能生物材料，用于术后快速组织密封、修复和手术部位保护。
