Hemorrhage Control During Brain Surgery

描述（由申请人提供）：大脑是一个高度血管化的器官，在其中进行的任何外科手术都不可避免地会破坏其脆弱的血管系统;解决脑外科手术期间的出血问题至关重要，因为颅骨有限空间内的过度出血会迅速导致严重的衰弱并发症和死亡。传统的出血控制技术对大脑的效用非常有限。脑外科手术期间的出血控制标准实际上几十年来没有改变，氧化纤维素、明胶和胶原蛋白是常用的材料;凝血酶通常与这些材料一起使用以加速止血。总的来说，与这些方法相关的主要问题是，（i）需要准备，（ii）与应用部位不共形且不粘附，（iii）缺乏透明度，因此可视化止血状态的能力有限，（iv）血液/哺乳动物来源的材料，因此存在疾病传播的风险，以及（v）肿胀。本课题将研制一种透明、生物相容性/生物降解性、可成型/贴合/粘附性的止血剂，用于脑外科手术中的止血。同时，我们将确认止血剂无细胞毒性潜力;随后将进行体内生物相容性试验。将在大鼠脑外科手术模型中进行体内有效性验证研究。 公共卫生相关性：在美国，每年有超过13万例神经外科手术在大脑上进行。大脑中有丰富的精致血管，在其中进行的任何外科手术都不可避免地破坏了结构。在脑外科手术中解决出血问题至关重要，因为脑内出血过多会迅速导致严重的衰弱并发症和死亡。由于血管的小尺寸和组织的精细，通常用于在各种外科手术中控制出血血管的典型技术（例如结扎和电烙术）在脑中具有非常有限的适用性。脑外科手术期间的出血控制标准实际上几十年来没有改变;目前用于控制出血的许多手术药物并不适合脑外科手术，并且许多这些产品是血液或哺乳动物来源的，这带来了疾病传播的风险。该项目的目标是开发一种非血液、非哺乳动物和天然材料的止血剂，用于脑外科手术中控制出血。

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.