In vivo Manipulation of Mechanical Loading: Using Real-time Biofeedback to Strategically Understand the Acute Biomechanical, Biochemical and Structural Changes Induced by Lower Extremity Loading

机械负荷的体内操纵：利用实时生物反馈有策略地了解下肢负荷引起的急性生物力学、生化和结构变化

• 批准号: 9762843
• 负责人: Jason R Franz
• 金额: $ 19.53万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9762843
• 关键词: Acute; Affect; American; Animals; Anterior Cruciate Ligament; Bilateral; Biochemical; Biochemistry; Biofeedback; Biomechanics; Cartilage; Collection; Cross-Over Studies; Cross-Sectional Studies; Crossover Design; Cues; Degenerative polyarthritis; Development; Diagnostic radiologic examination; Disease; Economic Burden; Experimental Models; Feedback; Future; Goals; Health; Hour; Human; Individual; Injury; Intervention; Investments; Joints; Kinetics; Knee; Knee Injuries; Knee Osteoarthritis; Laboratories; Lead; Limb structure; Link; Lower Extremity; Measures; Mechanics; Medical Research; Metabolism; Mission; Outcome; Outcome Measure; Pathogenesis; Patients; Public Health; Randomized; Reaction; Research; Research Personnel; Risk; Serum; Standardization; Structure; Testing; Time; Tissues; Ultrasonography; United States National Institutes of Health; Walking; Work; anterior cruciate ligament reconstruction; burden of illness; cost effective; effective intervention; high risk; improved; in vivo; innovation; insight; joint injury; joint loading; kinematics; ligament injury; mammalian COMP; mechanical load; novel; novel strategies; patient population; preservation; prevent; response; sex; theories; tissue biomarkers

Abstract Optimal mechanical loading is critical for joint tissue health, yet it remains unclear how to optimize loading following knee injury to prevent posttraumatic osteoarthritis (PTOA). The investigators' long-term goal is to develop individualized intervention strategies that target mechanical joint loading for the purpose of preventing PTOA. The objective of this R21 is to determine the acute effect of manipulating mechanical loading, using a real-time feedback paradigm to cue high-loading, low-loading and symmetrical loading conditions, on biomechanical, biochemical and structural measures related to PTOA pathogenesis in humans with anterior cruciate ligament reconstruction (ACLR). Recent evidence from the investigators' laboratory suggests that low- loading following injury may result in deleterious tissue metabolism and worse outcomes. Accordingly, the central hypothesis of this study is that the high-loading condition will result in greater tibiofemoral contact forces but also more knee excursion (less knee stiffness), resulting in a lesser immediate and delayed serum Cartilage Oligomeric Matrix Protein (COMP) response, as well as lesser cartilage deformation. The proposed study is needed because there is growing evidence, contrary to conventional theory, suggesting that patients with lesser mechanical loading following injury may be at higher risk for PTOA, and an intervention that cues higher-loading may be essential in mitigating that risk. Our study will demonstrate how manipulating mechanical load influences multiple critical outcomes needed to understand the mechanistic links between knee biomechanics, COMP response, and cartilage deformation. The central hypothesis will be tested with these two specific aims: 1) determine the acute effects of high-loading, low-loading, and symmetrical loading of the lower extremity on knee kinematics, knee kinetics and tibiofemoral joint contact forces during walking; 2) determine the effects of high-loading, low-loading and symmetrical loading during walking on serum COMP concentrations (immediately post and 3.5 hours post loading) and immediate sonography outcomes of femoral cartilage deformation. The proposed work is innovative as it: 1) incorporates a highly novel combination of outcome measures (biomechanical, joint tissue metabolism, and ultrasound of cartilage structure) that will lead to unprecedented mechanistic insight into the pathogenesis of PTOA; 2) strategically manipulates mechanical loading in multiple directions to determine how a known change in mechanical load will acutely influence outcomes, which is a stark departure from previous cross-sectional studies; and 3) utilizes a novel real-time feedback paradigm to cue changes in mechanical joint loading, which can easily be further developed into a future intervention. This R21 is significant, as the results will be pivotal in understanding how low-loading, high-loading and symmetrical loading influence changes in biomechanical, biochemical and cartilage deformation outcomes, which will lead to unprecedented mechanistic insight into PTOA pathogenesis and provide critical information regarding how best to direct loading following injury to prevent PTOA onset.

摘要 最佳的机械载荷对关节组织健康至关重要，但如何优化载荷仍不清楚 预防创伤后骨关节炎（PTOA）。研究人员的长期目标是 制定针对机械关节负荷的个性化干预策略，以预防 PTOA。本R21的目的是使用 实时反馈范例提示高负荷、低负荷和对称负荷条件， 生物力学，生物化学和结构的措施有关的PTOA发病机制，在人类与前 交叉韧带重建（ACLR）。研究人员实验室的最新证据表明，低- 损伤后的负荷可能导致有害的组织代谢和更坏的结果。因此 本研究的中心假设是高负荷条件将导致更大的胫股接触 力，但也有更多的膝关节偏移（更少的膝关节僵硬），导致更少的即时和延迟血清 软骨寡聚基质蛋白（COMP）反应，以及较少的软骨变形。拟议 研究是必要的，因为越来越多的证据表明，与传统理论相反， 损伤后机械负荷较小的患者发生PTOA的风险可能更高， 更高负载对于减轻风险可能是必要的。我们的研究将证明如何操纵 机械负荷影响多个关键结果，需要了解机械之间的联系， 膝关节生物力学、COMP反应和软骨变形。中心假设将被检验， 这两个具体目标：1）确定高负荷、低负荷和对称负荷的急性效应 下肢对膝关节运动学、膝关节动力学和胫股关节接触力的影响; 2） 测定步行过程中高负荷、低负荷和对称负荷对血清COMP的影响 浓度（即刻和加载后3.5小时）和股动脉的即刻超声结果 软骨变形拟议的工作是创新的，因为它：1）结合了一个高度新颖的组合， 结果测量（生物力学、关节组织代谢和软骨结构的超声）， 对PTOA发病机制的前所未有的机械见解; 2）战略性地操纵机械 在多个方向上加载，以确定机械载荷的已知变化将如何剧烈影响 结果，这是一个鲜明的背离以前的横截面研究;和3）利用一种新的实时 反馈范例提示机械关节负荷的变化，这可以很容易地进一步发展成一个 未来干预这个R21是重要的，因为结果将是关键的理解如何低负荷， 高负荷和对称负荷影响生物力学、生物化学和软骨的变化 变形的结果，这将导致前所未有的机制洞察PTOA发病机制， 提供关于如何在受伤后最好地引导负荷以防止PTOA发作的关键信息。

项目成果

Biofeedback augmenting lower limb loading alters the underlying temporal structure of gait following anterior cruciate ligament reconstruction.

• DOI: 10.1016/j.humov.2020.102685
• 发表时间: 2020-10
• 期刊: Human movement science
• 影响因子: 2.1
• 作者: Armitano-Lago C;Pietrosimone B;Davis-Wilson HC;Evans-Pickett A;Franz JR;Blackburn T;Kiefer AW
• 通讯作者: Kiefer AW

Cueing Changes in Peak Vertical Ground Reaction Force to Improve Coordination Dynamics in Walking.

• DOI: 10.1080/00222895.2021.1929810
• 发表时间: 2022
• 期刊: Journal of motor behavior
• 影响因子: 1.4
• 作者: Armitano-Lago C;Pietrosimone B;Evans-Pickett A;Davis-Wilson H;Franz JR;Blackburn T;Kiefer AW
• 通讯作者: Kiefer AW

Biomechanical effects of manipulating peak vertical ground reaction force throughout gait in individuals 6-12 months after anterior cruciate ligament reconstruction.

• DOI: 10.1016/j.clinbiomech.2020.105014
• 发表时间: 2020-06
• 期刊: Clinical biomechanics (Bristol, Avon)
• 作者: Evans-Pickett A;Davis-Wilson HC;Luc-Harkey BA;Blackburn JT;Franz JR;Padua DA;Seeley MK;Pietrosimone B
• 通讯作者: Pietrosimone B

Physical Activity Associates with T1rho MRI of Femoral Cartilage After Anterior Cruciate Ligament Reconstruction.

体力活动与前十字韧带重建后股骨软骨的 T1rho MRI 相关。

• DOI: 10.1249/mss.0000000000003318
• 发表时间: 2024
• 期刊: Medicine and science in sports and exercise
• 影响因子: 4.1
• 作者: Davis-Wilson,HopeC;Thoma,LouiseM;Franz,JasonR;Blackburn,JTroy;Longobardi,Lara;Schwartz,ToddA;Hackney,AnthonyC;Pietrosimone,Brian
• 通讯作者: Pietrosimone,Brian

Aberrant gait biomechanics in individuals with ACL reconstruction are magnified during treadmill walking.

• DOI: 10.1016/j.jbiomech.2022.110989
• 发表时间: 2022-03
• 期刊: Journal of biomechanics
• 影响因子: 2.4
• 作者: Dewig DR;Mills HR;Evans-Pickett A;Pietrosimone BG;Troy Blackburn J
• 通讯作者: Troy Blackburn J