Effects of Smoking on the Rotator Cuff Tendon-Bone Enthesis

吸烟对肩袖肌腱-骨附着的影响

• 批准号: 10714168
• 负责人: Zhaoxu Meng
• 金额: $ 22.49万
• 依托单位: CLEMSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-15 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10714168
• 关键词: Adopted; Adult; Adverse effects; Affect; American; Animal Model; Animals; Architecture; Behavior; Biochemical; Biomechanics; Bone Tissue; Cadaver; Calcium; Centers of Research Excellence; Cigarette; Collagen; Collagen Fiber; Complex; Computer Models; Control Groups; Coupled; Custom; Data; Dependence; Deterioration; Diameter; Distal; Elements; Environment; Failure; Fiber; Fluorescence; Foundations; Future; Generations; Goals; Grain; Histologic; Human; Image; Impairment; In Situ; Knowledge; Laws; Length; Measurement; Mechanics; Methods; Microscopic; Minerals; Modeling; Modulus; Morphology; Musculoskeletal System; Nicotine; Operative Surgical Procedures; Osmosis; Patients; Pattern; Phase; Physicians; Pump; Rattus; Reporting; Research; Risk; Risk Factors; Role; Rotator Cuff; Smoke; Smoking; South Carolina; Structure; Structure-Activity Relationship; Techniques; Tendon structure; Testing; Therapeutic; Tissues; Tracer; Validation; Visit; Work; Youth; bioimaging; bone; calcification; cigarette smoke; cigarette smoking; computer framework; crosslink; healing; high risk; high school; humerus; improved; innovation; insight; interest; mechanical properties; microscopic imaging; molecular dynamics; molecular scale; multi-scale modeling; novel; repair strategy; repaired; rotator cuff injury; rural area; sample fixation; second harmonic; soft tissue; supraspinatus muscle; surgery outcome; tool; treatment strategy; two-photon

SUMMARY Rotator cuff tendon tears account for more than 4.5 million physician visits and over 300,000 surgical repairs annually in the US. The healing rates of the tendon-bone interface, i.e., enthesis, remain low, despite continual improvements in fixation techniques. Moreover, pre-existing degeneration at the rotator cuff enthesis puts an estimated 17 million Americans at increased risk for rotator cuff impairment and tearing. A growing body of evidence indicates that cigarette smoking is an important risk factor. CDC data show that almost 13% of US adults smoke cigarettes, yet South Carolina rates are even higher at nearly 18%, with high school youth smoking cigarettes in SC at more than 3 times the US rate. Despite this significant impact, we still lack a fundamental understanding of the effects of cigarette smoking on the mechanical properties of the enthesis and the biomechanic mechanisms. Obstacles in formulating such understanding are partly attributed to (i) challenges in creating a realistic smoke exposure environment using well-controlled animal studies and (ii) the difficulties in characterizing the small-scale structural changes and correlating the structural changes with the deterioration of mechanical properties. We propose to utilize our custom-built automatic smoking chamber that resembles realistic cigarette smoking on a rat model, plus adopt an integrated experimental and computational approach to systematically understand the structure-function relationship of rat supraspinatus tendon-humerus enthesis and how it is impacted by cigarette smoking. The proposed studies will test the hypothesis that smoking directly affects the structure of collagen fibers plus the mineral gradient and distributions at the enthesis, all of which we further hypothesize will lead to deterioration of the enthesis by changing the microscopic deformation patterns. The specific aims are (1) to characterize the impact of smoking on the mechanical properties of the rotator cuff tendon-bone enthesis; (2) to delineate the changes from smoking on the multiphasic structures at the tendon- bone enthesis; (3) to construct a multiscale modeling framework that bridges the structures with the mechanical properties. We will integrate tissue biomechanics, bioimaging, and multiscale modeling to characterize the structure-function relationship of the enthesis, provide novel mechanistic data that will inform rotator cuff injury risk associated with cigarette smoking, and understand the underlying mechanisms. Once this approach is successfully applied, the tools and insights from this project can be transferred to other soft tissue-bone interfaces. Moreover, the new knowledge generated from this project, particularly the degenerative impact of smoking on rotator cuff tendon-bone enthesis, will lay the foundation for innovating treatment strategies for repairing the interfaces and improving the surgical outcomes of high-risk and/or rural area patients.

概括 肩袖肌腱眼泪占450万多个医师的访问和30万多个手术维修 每年在美国。尽管不断 固定技术的改进。此外，肩袖的既有变性 估计有1700万美国人有肩袖损伤和撕裂的风险增加。越来越多的身体 证据表明吸烟是重要的危险因素。 CDC数据表明，我们几乎13％ 成年人抽烟，但南卡罗来纳州的费率甚至更高，近18％，高中青年吸烟 SC中的香烟是美国利率的3倍以上。尽管产生了重大影响，但我们仍然缺乏基本 了解吸烟对ENTEMES和 生物力学机制。建立这种理解的障碍部分归因于（i） 使用良好控制的动物研究和（ii）困难 表征小规模的结构变化并将结构变化与恶化相关联 机械性能。我们建议使用类似于的定制自动吸烟室 在大鼠模型上吸烟逼真的香烟，加上采用集成的实验和计算方法 系统地了解大鼠肌腱 - 肌腱的结构功能关系和 吸烟如何影响它。拟议的研究将测试直接吸烟的假设 影响胶原纤维的结构以及矿物梯度和分布，我们所有这些 进一步的假设将通过改变微观变形模式来导致根的恶化。 具体目的是（1）表征吸烟对肩袖机械性能的影响 肌腱骨插入； （2）描述在肌腱上的多相结构上吸烟的变化 骨头（3）构建一个多尺度建模框架，该框架将结构与机械桥梁架起 特性。我们将整合组织生物力学，生物成像和多尺度建模，以表征 ENTEMES的结构功能关系，提供新的机械数据，以告知肩袖损伤 与吸烟相关的风险，并了解潜在的机制。一旦这种方法是 成功应用的，该项目的工具和见解可以转移到其他软组织骨上 接口。此外，该项目产生的新知识，尤其是 在肩袖肌腱骨的度上吸烟，将为创新治疗策略奠定基础 修复界面并改善高风险和/或农村地区患者的手术结局。