Effects of Smoking on the Rotator Cuff Tendon-Bone Enthesis

总结 肩袖肌腱撕裂导致超过450万次医生就诊和超过30万次手术修复 每年在美国。肌腱-骨界面的愈合率，即，尽管持续不断， 固定技术的改进。此外，在肩袖附着点预先存在的退化， 估计有1700万美国人肩袖损伤和撕裂的风险增加。越来越多的 有证据显示，吸烟是一个重要的危险因素。CDC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甚至更高，接近18%，高中生吸烟 SC中的香烟是美国的3倍多。尽管有这种重大影响，我们仍然缺乏一个基本的 了解吸烟对附着点机械性能的影响， 生物力学机制在形成这种理解方面的障碍部分归因于：（一） 使用良好控制的动物研究创建真实的烟雾暴露环境，以及（ii） 描述小规模的结构变化，并将结构变化与 力学性能我们建议使用我们定制的自动吸烟室， 在大鼠模型上真实吸烟，再加上采用综合实验和计算方法， 系统了解冈上肌腱-肱骨止点的结构-功能关系， 它是如何受到吸烟的影响的。拟议中的研究将检验吸烟直接影响健康的假设， 影响胶原纤维的结构，以及附着点处的矿物质梯度和分布，所有这些都是我们 进一步的假设将通过改变微观变形模式导致附着点的恶化。 具体目的是（1）表征吸烟对肩袖力学性能的影响 腱-骨附着点;（2）描绘吸烟对腱处多相结构的变化- （3）构建一个多尺度建模框架，将结构与机械连接起来， 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 附着点的结构-功能关系，提供了新的机械数据，将告知肩袖损伤 与吸烟相关的风险，并了解潜在的机制。一旦这种方法被 成功应用，该项目的工具和见解可以转移到其他软组织-骨 接口。此外，该项目产生的新知识，特别是 吸烟对肩袖肌腱-骨附着点，将奠定基础，创新治疗策略， 修复接口并改善高危和/或农村地区患者的手术结果。

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.