Hemorrhage Control During Brain Surgery

描述(申请人提供)：大脑是一个高度血运丰富的器官，在其中进行的任何手术都不可避免地破坏其脆弱的血管系统；解决脑外科手术中的出血问题至关重要，因为在颅骨有限的空间内过度出血会很快导致严重的虚弱并发症和死亡。传统的止血技术对大脑的效用非常有限。脑外科手术中控制出血的标准几十年来几乎没有改变，常用的材料是氧化纤维素、明胶和胶原；凝血酶经常与这些材料一起使用以加速止血。总体而言，与这些方法相关的主要问题是：(I)需要准备；(Ii)非适形和非粘附性；(Iii)缺乏透明度，因此显示止血状态的能力有限；(Iv)血液/哺乳动物来源的材料，因此疾病传播的风险；以及(V)肿胀。在本项目中，我们将研制一种透明、生物相容/可生物降解、可形成/顺应性/粘附性的止血剂，旨在控制脑外科手术中的出血。同时，我们将验证止血剂缺乏细胞毒性潜力；随后将进行体内生物相容性测试。体内药效验证研究将在大鼠脑外科模型上进行。 与公共健康相关：在美国，每年进行的脑部神经外科手术超过13万例。大脑富含脆弱的血管，在其中进行的任何外科手术都不可避免地破坏了大脑的结构。解决脑外科手术中的出血问题至关重要，因为脑内出血过多会很快导致严重的虚弱并发症和死亡。由于血管的小尺寸和组织的微妙，在各种外科手术中常用的控制出血血管的典型技术，如结扎术和电灼术，在大脑中的适用性非常有限。脑外科手术中控制出血的标准几十年来几乎没有改变；目前用于控制出血的许多手术辅助设备并没有针对脑外科进行优化，而且这些产品中的许多是血液或哺乳动物来源的，具有疾病传播的风险。该项目的目标是开发一种非血液、非哺乳动物和天然材料为基础的止血剂，优化用于控制脑外科手术中的出血。

DESCRIPTION (provided by applicant): The brain is a highly vascularized organ and any surgical procedure performed in it inevitably disrupts its delicate vasculature; addressing bleeding during brain surgery is of utmost importance, as excessive bleeding within the confined space of the skull can quickly lead to serious debilitating complications and death. Conventional techniques for bleeding control have very limited utility for the brain. The standard for bleeding control during brain surgery has practically not changed for many decades, with oxidized cellulose, gelatin and collagen as the commonly used materials; thrombin is often deployed in conjunction with these materials to hasten hemostasis. Collectively, the main issues associate with these approaches are, (i) require preparation, (ii) non-conformal and non-adhesive to the site of application, (iii) lack transparency and thus limited capacity for visualizing the status of hemostasis, (iv) material of blood/mammalian origin and thus the risk of disease transmission, and (v) swelling. In this project, we will formulate a transparent, biocompatible/biodegradable and formable/conformable/adhesive hemostatic agent aiming for controlling the bleeding during brain surgery. In parallel, we will validate the lack of cytotoxicity potential of the hemostatic agent; this will be followed by in vivo biocompatibility testing. The in vivo efficacy validation study will be performed in rat brain surgery model. PUBLIC HEALTH RELEVANCE: Over 130,000 neurosurgical procedures are performed on the brain in the US each year. The brain is rich in delicate blood vessels and any surgical procedure performed in it inevitably disrupts the structure. Addressing bleeding during brain surgery is of utmost importance, as excessive bleeding within the brain can quickly lead to serious debilitating complications and death. Due to the small size of the vessels and the delicacy of the tissue, typical techniques such as ligature and electrocautery commonly utilized for controlling bleeding vessels in various surgical procedures have very limited applicability in the brain. The standard for bleeding control during brain surgery has practically not changed for many decades; many of the surgical adjuncts currently being utilized to control bleeding are not optimized for brain surgery and many of these products are blood or mammalian derived, which carry the risk of disease transmission. The goal of this project is to develop a non-blood, non-mammalian and natural material based hemostatic agent optimized for controlling bleeding during brain surgery.