Bioengineered Skin Sealants

摘要

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.