A new experimental model of knee joint trauma

一种新的膝关节损伤实验模型

• 批准号: 8308415
• 负责人: TAMMY L. HAUT DONAHUE
• 金额: $ 16.35万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8308415
• 关键词: Acute; Address; Animal Model; Animals; Anterior Cruciate Ligament; Apoptosis; Appearance; Arthralgia; Bone Density; Cartilage; Cell Density; Cell Survival; Chronic; Chronic Disease; Clinical; Contralateral; Contusions; Data; Degenerative Disorder; Degenerative polyarthritis; Degradation Pathway; Development; Devices; Disease; Epidemic; Event; Exercise; Exhibits; Experimental Models; Future; Goals; Gold; Health; Healthcare Systems; Histology; Image; Inflammation; Injury; Intervention; Intervention Studies; Investigation; Joint Instability; Joint repair; Joints; Knee; Knee Injuries; Knee Osteoarthritis; Knee joint; Lead; Life; Life Style; Limb structure; Literature; Longitudinal Studies; Lower Extremity; Magnetic Resonance; Magnetic Resonance Imaging; Maintenance; Measures; Mechanics; Meniscus structure of joint; Methods; Modeling; Morphology; Operative Surgical Procedures; Orthopedics; Oryctolagus cuniculus; Outcome; Pain; Pathology; Patients; Pharmacologic Substance; Phase; Process; Property; Recreation; Rehabilitation therapy; Research; Research Proposals; Risk; Scanning; Societies; Soft Tissue Injuries; Sports; Structure; Surgical Models; Testing; Tissues; Trauma; Traumatic Rupture; anterior cruciate ligament rupture; arthropathies; articular cartilage; bone; cost; design; disability; improved; in vivo; joint injury; joint loading; knee replacement arthroplasty; ligament injury; musculoskeletal injury; novel; pressure; prevent; reconstruction; repaired; sham surgery; substantia spongiosa; tool

DESCRIPTION (provided by applicant): Musculoskeletal injuries and joint disorders due to sports, recreation and exercise (SRE) have reached epidemic proportions as our society attempts to develop a healthier lifestyle. Participation in many SRE activities requires maintenance of lower- extremity joint health, yet such involvement presents an inherent risk of developing exercise-induced or traumatic musculoskeletal injuries. Treatment of these injuries, particularly to the knee joint, is paramount in the retention of a healthy lifestyle. Studies of patients suffering knee injuries, such as to the anterior cruciate ligament (ACL) and meniscus, show that even with surgical reconstruction after traumatic rupture there is a significant increase in the risk of a long term, chronic disease called osteoarthritis (OA). We hypothesize that this disease process may be precipitated by occult damage to the other structures of the knee as a result of the high compressive joint loads that occur during the acute injury to the knee. High joint contact pressures during traumatic impaction help explain the large number of injury cases that exhibit bone bruises, or occult bone microcracks, and injury to overlying cartilage that occurs following injury- producing jump landings that often initiate the chronic disease process. Surprisingly, to date, there is no established animal model to study the long-term consequences of traumatic injury to the knee following rupture of the ACL and meniscal tissue. The current literature documents a joint instability model of osteoarthritis in which the ACL and/or meniscus is surgically damaged. However, this model fails to address the high contact pressures and tissue injuries generated in the joint during the acute event. This research team has recently developed a live animal model for the study of traumatic ACL and meniscus injury. In order to study the changes occurring in the tissues of the knee during traumatic injury and establish preliminary data for future clinical intervention studies, the current study will establish and characterize a new, in vivo animal model of traumatic joint injury. We hypothesize that there will be significantly more degeneration of the articular cartilage, remaining untorn menisci and subchondral bone during the degenerative phase of the traumatic versus the surgical model to 12 weeks post-trauma. The development of future orthopaedic treatments will hinge on accurate experimental models of post-injury inflammation, alignment, and pain issues. The proposed research has the potential to revolutionize the understanding of traumatic joint injury that leads to a post-traumatic OA by greatly altering the gold standard model used to study the pathology of knee OA. Future implementation of this characterized model will encourage translational treatments and interventions, such as rehabilitation therapies or pharmaceutical interventions, which will delay and potentially prevent joint pain, disability, and the eventual need for total knee arthroplasty.

描述（由申请人提供）：由于运动，娱乐和锻炼（SRE）引起的肌肉骨骼损伤和关节疾病已经达到流行病的比例，因为我们的社会试图发展更健康的生活方式。参与许多SRE活动需要维持下肢关节健康，但这种参与存在发生运动诱导或创伤性肌肉骨骼损伤的固有风险。治疗这些损伤，特别是膝关节损伤，对于保持健康的生活方式至关重要。对膝关节损伤患者（如前交叉韧带（ACL）和半月板）的研究表明，即使在创伤性断裂后进行手术重建，也会显着增加患长期慢性疾病（称为骨关节炎（OA））的风险。我们假设，这种疾病的过程可能是由于在急性损伤膝关节期间发生的高压缩关节负荷导致的膝关节其他结构的隐匿性损伤而加速的。创伤性撞击过程中的高关节接触压力有助于解释大量的损伤病例，这些病例表现出骨挫伤或隐匿性骨微裂纹，以及在产生损伤的跳跃着陆后发生的上覆软骨损伤，这些损伤通常引发慢性疾病过程。令人惊讶的是，迄今为止，还没有建立动物模型来研究ACL和踝关节组织破裂后膝关节创伤性损伤的长期后果。当前文献记录了骨关节炎的关节不稳定模型，其中ACL和/或半月板手术损伤。然而，该模型未能解决急性事件期间关节中产生的高接触压力和组织损伤。该研究小组最近开发了一种用于研究创伤性ACL和半月板损伤的活体动物模型。为了研究创伤性损伤过程中膝关节组织发生的变化，并为未来的临床干预研究建立初步数据，本研究将建立并表征一种新的创伤性关节损伤的体内动物模型。我们假设，在创伤的退行性阶段与手术模型至创伤后12周期间，关节软骨、剩余未撕裂的软骨和软骨下骨的退行性变将显著更多。未来骨科治疗的发展将取决于损伤后炎症，对齐和疼痛问题的准确实验模型。拟议的研究有可能通过极大地改变用于研究膝关节OA病理学的金标准模型，彻底改变对导致创伤后OA的创伤性关节损伤的理解。这种特征模型的未来实施将鼓励转化治疗和干预，例如康复治疗或药物干预，这将延迟并可能预防关节疼痛、残疾以及最终对全膝关节置换术的需求。

项目成果

Chronic changes in the articular cartilage and meniscus following traumatic impact to the lapine knee.

• DOI: 10.1016/j.jbiomech.2014.11.038
• 发表时间: 2015-01-21
• 期刊: JOURNAL OF BIOMECHANICS
• 影响因子: 2.4
• 作者: Fischenich, Kristine M.;Button, Keith D.;Coatney, Garrett A.;Fajardo, Ryan S.;Leikert, Kevin M.;Haut, Roger C.;Donahue, Tammy L. Haut
• 通讯作者: Donahue, Tammy L. Haut

Efficacy of P188 on lapine meniscus preservation following blunt trauma.

钝性创伤后，P188对打衣弯月板保存的功效。

• DOI: 10.1016/j.jmbbm.2015.03.008
• 发表时间: 2015-07
• 期刊: JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
• 影响因子: 3.9
• 作者: Coatney, Garrett A.;Abraham, Adam C.;Fischenich, Kristine M.;Button, Keith D.;Haut, Roger C.;Donahue, Tammy L. Haut
• 通讯作者: Donahue, Tammy L. Haut

Assessment of cortical and trabecular bone changes in two models of post-traumatic osteoarthritis.

• DOI: 10.1002/jor.22975
• 发表时间: 2015-12
• 期刊: Journal of orthopaedic research : official publication of the Orthopaedic Research Society
• 作者: Pauly HM;Larson BE;Coatney GA;Button KD;DeCamp CE;Fajardo RS;Haut RC;Haut Donahue TL
• 通讯作者: Haut Donahue TL

An optimized transversely isotropic, hyper-poro-viscoelastic finite element model of the meniscus to evaluate mechanical degradation following traumatic loading.

• DOI: 10.1016/j.jbiomech.2015.02.028
• 发表时间: 2015-06-01
• 期刊: JOURNAL OF BIOMECHANICS
• 影响因子: 2.4
• 作者: Wheatley, Benjamin B.;Fischenich, Kristine M.;Button, Keith D.;Haut, Roger C.;Donahue, Tammy L. Haut
• 通讯作者: Donahue, Tammy L. Haut

Acute cell viability and nitric oxide release in lateral menisci following closed-joint knee injury in a lapine model of post-traumatic osteoarthritis.

• DOI: 10.1186/1471-2474-15-297
• 发表时间: 2014-09-06
• 期刊: BMC musculoskeletal disorders
• 影响因子: 2.3
• 作者: Killian ML;Haut RC;Haut Donahue TL
• 通讯作者: Haut Donahue TL