Preventing Post-Laminectomy Peridural Fibrosis

描述(由申请人提供)：术后硬膜外纤维化(疤痕形成)是腰椎小间盘切除术的相关事件，它显著增加了脊柱翻修手术的风险。疤痕组织的形成是正常愈合过程的一部分，也是椎板切除手术不可避免的后果。硬膜外疤痕形成可导致神经根周围的纤维粘连，通过困住退出的神经根而施加张力，导致机械拴系，最终导致神经损伤；它还可导致脊髓受压，导致随后的疼痛。腰椎手术后硬脑膜的致密粘连和过度疤痕可导致神经根性疼痛、下腰痛，甚至蛛网膜炎。所有这些都可能导致需要随后的重新操作。该项目的目标是开发一种生物相容和可生物降解的原位凝胶水凝胶系统，以瞬时封闭椎板切除部位，防止过度纤维组织形成引起的粘连。水凝胶配方的性能特征将首先得到优化；随后将对其生物兼容性进行验证。该项目将在兔椎板切除硬膜外纤维化模型上进行体内疗效评估后结束。这个第一阶段的SBIR项目将为开发未来的治疗方法奠定基础，以大大降低涉及椎板切除程序的翻修手术的比率。公共卫生相关性：腰椎间盘摘除已经发展成为美国最常见的神经外科手术，由于神经根性腿部和背部疼痛的流行问题，每年有近30万例手术，这相当于每年1500万次医生就诊。据估计，每年给社会造成的财政负担超过500亿美元。瘢痕组织的形成是正常愈合过程的一部分，也是椎板切除手术不可避免的后果。术后硬膜外纤维化(瘢痕形成)是腰椎小间盘切除术的相关事件，它显著增加了脊柱翻修手术的风险。广泛的硬膜外疤痕形成可导致神经根周围的纤维粘连，通过困住退出的神经根而施加张力，导致机械拴系，最终导致神经损伤；它还可导致脊髓受压，导致随后的疼痛。腰椎手术后硬脑膜的致密粘连和过度疤痕可导致神经根性疼痛、下腰痛，甚至蛛网膜炎。目前腰椎小间盘切除术后的再手术率估计为9-14%。尽管有更好的治疗选择，但在1990年初(1990年至1993年)与1990年末(1997年至2000年)接受S治疗的患者中，因退行性疾病(椎板切除、椎间盘切除)而行减压手术后的再次手术率有所上升。本项目的目标是开发一种生物相容、可生物吸收和原位可凝胶的聚合物载体，作为椎板切除术后的抗粘连疗法，旨在提高微椎间盘切除术的疗效，从而降低再手术率。

DESCRIPTION (provided by applicant): Post-operative peridural fibrosis (scarring) is an associated event of lumbar microdiskectomy, and it significantly increases the hazard of revision spine surgery. The formation of scar tissue is part of the normal healing process and also an unavoidable consequence of procedures involving laminectomy. Epidural scar formation can result in fibrous adhesions around nerve roots imposing tension by entrapping the exiting nerve root resulting in mechanical tethering and eventually nerve damage; it can also cause compression of the spinal cord leading to subsequent pain. Dense adhesions and excessive scarring of the dura following lumbar surgery can cause radicular pain, low back pain, and even arachnoiditis. All these could result in the need for subsequent re-operation. The goal of this project is to develop a biocompatible and biodegradable in situ gelable hydrogel system to transiently seal the laminectomy site to prevent adhesion caused by excessive fibrotic tissue formation. The performance characteristics of the hydrogel formulations will initially be optimized; this is followed by validation of its biocompatibility. The project will be concluded after performing in vivo efficacy evaluations in rabbit laminectomy epidural fibrosis models. This Phase I SBIR project will set the stage for developing future treatment to greatly reduce the rate of revision surgery on procedures involving laminectomy. PUBLIC HEALTH RELEVANCE: Lumbar diskectomy has evolved as the most common neurosurgical procedure in the U.S., with nearly 300,000 procedures performed annually because of the epidemic problem of radicular leg and back pain, which translates into 15 million annual physician visits per year. It has been estimated that the financial burden on society exceeds $50 billion annually. The formation of scar tissue is part of the normal healing process and also an unavoidable consequence of procedures involving laminectomy Post-operative peridural fibrosis (scarring) is an associated event of lumbar microdiskectomy, and it significantly increases the hazard of revision spine surgery. Extensive epidural scar formation can result in fibrous adhesions around nerve roots imposing tension by entrapping the exiting nerve root resulting in mechanical tethering and eventually nerve damage; it can also cause compression of the spinal cord leading to subsequent pain. Dense adhesions and excessive scarring of the dura following lumbar surgery can cause radicular pain, low back pain, and even arachnoiditis. Current re-operation rates after lumbar microdiskectomy are estimated at 9-14%. Re-operation rates after decompressive surgery for degenerative conditions (laminectomy, diskectomy) has increased in patients treated in the early (1990-1993) versus late (1997-2000) 1990's, despite better treatment options. The goal of this project is to develop a biocompatible, bioresorbable and in situ gelable polymeric vehicle to be administered as a "post-laminectomy anti-adhesion therapy" designed to enhance the efficacy for microdiskectomy leading to decrease in the rate of re-operation.