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.

摘要 肩袖肌腱撕裂占超过450万次内科就诊和30多万次手术修复 每年在美国。肌腱-骨界面，即末端的愈合率仍然很低，尽管持续的 固定技术的改进。此外，肩袖连接处预先存在的退行性变使 估计有1700万美国人肩袖损伤和撕裂的风险增加。不断增长的 有证据表明，吸烟是一个重要的危险因素。疾控中心的数据显示，近13%的美国人 成年人吸烟，但南卡罗来纳州的吸烟率更高，接近18%，高中生吸烟 南加州的烟草率是美国的3倍以上。尽管产生了重大影响，但我们仍然缺乏根本的 了解吸烟对牙槽突机械性能的影响 生物力学机制。在形成这种理解方面的障碍部分归因于：(I)在 使用受控良好的动物研究创造一个真实的烟雾暴露环境，以及(Ii) 刻画小尺度结构变化并将结构变化与气候变差联系起来 机械性能。我们计划利用我们定制的自动吸烟室，类似于 在老鼠模型上真实吸烟，并采用集成的实验和计算方法来 系统了解大鼠冈上肌腱-肱骨末端的结构与功能关系 吸烟对它的影响。拟议中的研究将检验直接吸烟的假设 影响胶原纤维的结构加上矿物质的梯度和在末端的分布，所有这些我们 进一步的假设将通过改变显微变形模式而导致凹陷的恶化。 具体目的是(1)表征吸烟对肩袖机械性能的影响 肌腱-骨吻合；(2)描述吸烟对肌腱多相结构的影响 (3)构建一个多尺度建模框架，将结构与机械连接起来 属性。我们将结合组织生物力学、生物成像和多尺度建模来描述 吻合部的结构-功能关系，为肩袖损伤提供新的机制数据 与吸烟相关的风险，并了解其潜在的机制。一旦这种方法成为 成功应用，本项目的工具和见解可以移植到其他软组织-骨 接口。此外，该项目产生的新知识，特别是 在肩袖肌腱-骨端吸烟，将为创新治疗策略奠定基础 修复界面并改善高危和/或农村地区患者的手术结果。