Collagenolysis of the transverse carpal ligament

腕横韧带胶原溶解

基本信息

批准号：
10200675
负责人：
Zong-Ming Li
金额：
$ 19.65万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-23 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10200675
关键词：
3-Dimensional Acoustics Activities of Daily Living Anatomy Animals Area Biological Cadaver Carpal Tunnel Syndrome Clinic Clinical Trials Collagen Collagen Fiber Contracture Custom Deposition Disease Dose Dupuytren&apos s Contracture FDA approved Flexor Future General Population Goals Hand Hand Strength Health Care Costs Hour Human Hypertrophy Image In Situ In Vitro Injections Knowledge Length Ligaments Measures Mechanics Medical Care Costs Microbial Collagenase Morphology Motion Muscle Nerve Operative Surgical Procedures Pain Pathologic Patients Pharmaceutical Preparations Productivity Property Public Health Radiation Reproducibility Robot Robotics Scanning Site Structure Surgical complication System Technology Tendon structure Testing Thick Time Tissues Treatment Efficacy Ultrasonography United States carpus bone collagenase grasp in vivo innovation mechanical properties median nerve nerve decompression novel pressure reconstruction response robot assistance virtual

项目摘要

ABSTRACT Carpal tunnel syndrome (CTS) is the most common hand disorder, and nearly half a million carpal tunnel release surgeries are performed annually in the United States. During surgery, the transverse carpal ligament (TCL) is transected to decompress the median nerve. However, transecting the TCL reduces grip strength, causes pillar pain, results in greater carpal bone motion, and may damage the surrounding nerves, vessels or tendons. To avoid these surgical complications, innovative treatment solutions with non-operative approaches are sorely needed. Transection of the TCL as a surgical treatment for carpal tunnel syndrome is analogous to surgical fasciectomy for Dupuytren's contracture. As collagenase injection successfully treats Dupuytren's contracture, it is compelling to explore this collagenolytic effect on the TCL. Our long-term goal is to develop a novel non-operative treatment for carpal tunnel syndrome by enzymatically degrading the TCL. The objective of this project is to inject collagenase into the TCL and evaluate its enzymatic effect on TCL morphology and mechanics using state-of-the-art robotic and ultrasound technologies. Our central hypothesis is that collagenase effectively degrades the TCL, leading to decreased TCL thickness and stiffness in vitro as well as increased TCL length and arch area in situ. This hypothesis will be tested with two specific aims: (1) to investigate dose- and time-dependent collagenolytic effects on the morphological and mechanical properties of the TCL in vitro, and to identify an optimal collagenase dose that can achieve effective and safe collagenolysis of the TCL after 24 hours; (2) to examine the changes in structural properties of the TCL in situ in response to collagenase injections and determine an injection configuration to achieve TCL elongation of 2 mm. In Aim 1, collagenase at various doses will be injected into TCL tissues dissected from cadaveric hands. B-mode and acoustic radiation force impulse (ARFI) ultrasound imaging will be performed to measure thickness and stiffness changes over time up to 24 hours. The stiffness of the TCL will be derived from shear wave velocity measured by ARFI. We will also identify the minimum effective collagenase dose that can achieve 80% reduction of thickness and shear wave velocity at 24 hours. In Aim 2, collagenase will be injected using the optimal dose determined in Aim 1 along the longitudinal midline of the TCL in situ. Carpal tunnel pressure will be applied to obtain local strain at the injection sites and gross tissue elongation, which will be used to determine an injection to achieve the desired TCL elongation. Robot-assisted collagenase injection and ultrasound scanning will be performed to achieve precise injection and reproducible scanning for TCL reconstruction. The implementation of the proposed project is the critical first step to exploring the possibility of collagenolysis of the TCL as a novel non-operative treatment for CTS. The knowledge obtained from this project will guide future in situ carpal tunnel studies, in vivo animal studies, and clinical trials, tapping into the potential of collagenase injection as a novel non-operative treatment for CTS.

抽象的腕管综合症 (CTS) 是最常见的手部疾病，近 50 万腕管患者美国每年都会进行释放手术。在手术过程中，腕横韧带 (TCL) 被横断以减压正中神经。然而，横切 TCL 会降低握力，引起支柱疼痛，导致腕骨运动更大，并可能损害周围的神经、血管或肌腱。为了避免这些手术并发症，采用非手术方法的创新治疗解决方案是迫切需要的。 TCL 横断术作为腕管综合征的手术治疗方法类似于手术筋膜切除术治疗掌腱膜挛缩症。胶原酶注射成功治疗掌腱膜挛缩症挛缩，探索胶原蛋白溶解对 TCL 的影响是很有意义的。我们的长期目标是发展通过酶降解 TCL 来非手术治疗腕管综合征。的目标该项目是将胶原酶注入TCL中，并评估其酶促作用对TCL形态和使用最先进的机器人和超声波技术的机械师。我们的中心假设是胶原酶有效降解 TCL，导致体外 TCL 厚度和硬度降低，并且原位增加 TCL 长度和足弓面积。该假设将通过两个具体目标进行检验：（1）研究剂量和时间依赖性胶原蛋白溶解对形态和机械特性的影响 TCL 体外实验，并确定可实现有效且安全的胶原溶解的最佳胶原酶剂量 24小时后TCL的； (2) 原位检验 TCL 结构特性的变化胶原酶注射并确定注射配置以实现 TCL 伸长 2 毫米。在目标 1 中，不同剂量的胶原酶将被注射到从尸体手上解剖的 TCL 组织中。 B 型和将进行声辐射力脉冲（ARFI）超声成像来测量厚度和刚度随时间变化长达 24 小时。 TCL 的刚度由剪切波速度得出由 ARFI 测量。我们还将确定可达到 80% 的最小有效胶原酶剂量 24小时厚度和剪切波速的减少。在目标 2 中，将使用注射胶原酶目标 1 中沿 TCL 纵向中线原位确定的最佳剂量。腕管压力会应用于获得注射部位的局部应变和总组织伸长，这将用于确定注射次数以达到所需的 TCL 伸长率。机器人辅助胶原酶注射和将进行超声波扫描，为TCL实现精准注射和可重复扫描重建。拟议项目的实施是探索可能性的关键第一步 TCL 胶原溶解作为 CTS 的一种新型非手术治疗方法。由此获得的知识该项目将指导未来的原位腕管研究、体内动物研究和临床试验，利用胶原酶注射作为一种新型非手术治疗 CTS 的潜力。