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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.

摘要腕管综合征（CTS）是最常见的手部疾病，每年在美国进行释放手术。在手术中，腕横韧带 (TCL)切断正中神经然而，横断TCL会降低握力，导致支柱疼痛，导致更大的腕骨运动，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方案是非常需要的。横断TCL作为腕管综合征的手术治疗类似于筋膜切除术治疗掌腱膜挛缩症由于胶原酶注射成功治疗了Dupuytren's，因此，探索这种对TCL的胶原溶解作用是引人注目的。我们的长期目标是发展一个通过酶促降解TCL的新的非手术治疗腕管综合征。的目标本课题将胶原酶注射到TCL中，评价其对TCL形态学的影响，使用最先进的机器人和超声波技术。我们的核心假设是，胶原酶有效地降解TCL，导致体外TCL厚度和刚度降低，增加了TCL长度和原位弓面积。这一假设将以两个具体目标进行检验：（1）研究剂量和时间依赖性的胶原溶解作用，体外TCL，并确定可实现有效和安全的胶原溶解的最佳胶原酶剂量（2）原位检查TCL的结构特性响应于胶原酶注射并确定注射配置以实现2mm的TCL伸长。在目标1中，将不同剂量的胶原酶注射到从尸体手解剖的TCL组织中。b模式和将进行声辐射力脉冲（ARFI）超声成像以测量厚度，硬度随时间变化长达24小时。TCL的刚度将从剪切波速度导出由ARFI测量。我们还将确定能达到80%的最低有效胶原酶剂量 24小时时的厚度和剪切波速度的减小。在目标2中，胶原酶将使用目标1中确定的最佳剂量，沿着TCL的纵向中线原位。腕管综合征用于获得注射部位的局部应变和总组织伸长，这将用于确定注射以实现期望的TCL伸长。机器人辅助胶原酶注射，将进行超声扫描，以实现TCL的精确注射和可重复扫描重建实施拟议项目是探索以下可能性的关键第一步： TCL的胶原溶解作为CTS的新型非手术治疗。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，胶原酶注射作为一种新的CTS非手术治疗的潜力。