Enabling ACL Repair Using Proprietary Collagen Device

使用专有的胶原蛋白设备实现 ACL 修复

• 批准号: 7746312
• 负责人: Kurt Paul Spindler
• 金额: $ 15.78万
• 依托单位: CONNECTIVE ORTHOPAEDICS, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2010-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7746312
• 关键词: Adult; Allografting; Autologous; Autologous Transplantation; Biomechanics; Blood Platelets; Canis familiaris; Cellularity; Clinical; Collagen; Contralateral; Data; Degenerative polyarthritis; Development; Devices; Direct Costs; Euthanasia; Evaluation; Facilities and Administrative Costs; Failure; Family suidae; Foundations; Future; Gait; Goals; Gold; Harvest; Healed; Health system; Histologic; Histology; Injury; Joint Laxity; Knee; Knee joint; Measures; Medial; Medial meniscus structure; Meniscus structure of joint; Miniature Swine; Modeling; Morbidity - disease rate; Operative Surgical Procedures; Pain; Pathology; Persons; Phase; Postoperative Period; Procedures; Productivity; Property; Rehabilitation therapy; Research Personnel; Resources; Site; Techniques; Technology; Time; anterior cruciate ligament reconstruction; anterior cruciate ligament rupture; clinically relevant; cost; experience; healing; injury and repair; innovation; meetings; minimally invasive; novel; osteochondral tissue; public health relevance; reconstruction; repaired; research study; standard care

DESCRIPTION (provided by applicant): A collagen-platelet composite has been developed and validated by the investigators in a canine model to heal partial ACL tears both biomechanically and histologically. Further, the platelet collagen device has been shown in a porcine model to promote ACL repair. The change to the canine model is advantageous to evaluate our device in a known clinically relevant ACL injury, repair, reconstruction model. This model will allow evaluation for development of osteoarthritis (OA), validated gait/lameness scores, arthroscopic inspection of the knee, comparison of biomechanical results and histology to known standards, and has the potential to control rehabilitation in the future. Further, the huge size of adult, skeletally mature porcine and the limitations on supply and expense of the "minipig" are avoided, thus reducing cost of evaluation of this device. The PI has extensive experience with canine knees with ACL reconstruction, meniscus injury models, osteochondral allograft and autograft procedure in addition to partial ACL tear model (biomechanical and histological healing with our device). The proposed study has the following Aims. Aim 1: Evaluate the clinical function of healing collagen-platelet composite ACL repair by validated canine lameness score. Hypothesis 1: The lameness scores will decrease over four to twelve weeks with successful healing and be associated with less medial meniscus tears and chondromalacia on medial femoral condyle and medial tibial plateau at euthanasia. Our goal is met when 80% < lameness of 3. Aim 2: Delineate the effects of the collagen-platelet composite on knee joint laxity (anteroposterior/axial) after 12 weeks of healing. Hypothesis 2: The AP laxity values of the ACL repair knees treated with the concentrated collagen-platelet composite will be within range of postoperative laxity seen after ACL reconstructions (~250% of the intact contralateral knee). Our goal is met by 80% achieving this value. Aim 3: Measure the structural properties (maximum load to failure/linear stiffness) and histology (cellularity/vascularity) of the healing ACL repair with collagen-platelet composite after 12 weeks. Hypothesis 3: The structural properties of the ACL repairs treated with a collagen-platelet composite will be greater than 20% of intact contralateral ACL. Our goal is met by 80% achieving this value. The PI and investigators have the required expertise and resources to evaluate this promising novel device for an innovative ACL repair in a known clinically relevant canine knee ACL model. Ten canines will undergo unilateral ACL repair and be evaluated clinically (lameness and intraarticular pathology), joint laxity, and structural properties of healing ACL repair. The contralateral normal knee will serve as control and prior completed canine and porcine experiments (ACL repair, reconstruction, and deficient) by this investigative team will serve as historical controls. Successful completion of Phase I will be defined by a priori established criteria for intact repair, AP laxity, load at yield, lameness and meniscus status at 12 weeks. PUBLIC HEALTH RELEVANCE: Over 300,000 ACL reconstructions (ACLRs) are performed each year at an estimated cost to the U.S. health system of $2.5 billion a year. Use of our proprietary Collagen Platelet Composite with primary repair will significantly reduce procedure time and rehabilitation time, eliminate complications and morbidity associated with graft harvesting, and preserve the broad insertion sites and proprioceptive function of the native ACL, which will dramatically cut the pain and lost productivity of reconstruction surgery. Preliminary estimates show that repair with our technology can save the U.S. health system over $1 billion in direct cost and substantially more in indirect costs by regaining thousands of person-years of lost productivity.

描述(申请人提供)：研究人员已经开发了一种胶原-血小板复合材料，并在犬模型上进行了验证，以从生物力学和组织学的角度治愈部分前交叉韧带撕裂。此外，这种血小板胶原蛋白装置已经在猪模型中被证明可以促进前交叉韧带的修复。犬模型的改变有利于评估我们的装置在已知临床相关的前交叉韧带损伤、修复和重建模型中的作用。该模型将能够评估骨关节炎(OA)的发展，验证步态/跛行评分，膝关节关节镜检查，生物力学结果和组织学与已知标准的比较，并有可能控制未来的康复。此外，还避免了成年、骨骼成熟的猪的巨大体型和“小型猪”的供应和费用限制，从而降低了该设备的评估成本。PI在前交叉韧带重建、半月板损伤模型、同种异体骨软骨移植和自体软骨移植手术以及部分前交叉韧带撕裂模型(使用我们的装置进行生物力学和组织学愈合)方面拥有丰富的经验。拟议的研究有以下目标。目的1：通过验证犬跛行评分，评价胶原-血小板复合体修复前交叉韧带的临床作用。假设1：随着愈合的成功，跛行评分将在4到12周内降低，并且与安乐死时股骨内侧髁和胫骨内侧平台的内侧半月板撕裂和软骨软化的减少有关。我们的目标是当80%的跛行达到3。目的2：描述12周愈合后胶原-血小板复合材料对膝关节松弛(前后/轴向)的影响。假设2：用浓缩胶原-血小板复合材料治疗的前交叉韧带修复膝关节的AP松弛值将在重建后的松弛范围内(约为健侧膝关节的250%)。我们的目标是通过80%实现这一价值来实现。目的：测量12周后胶原-血小板复合材料修复前交叉韧带的结构特性(最大载荷/线刚度)和组织学特性(细胞性/血管性)。假设3：用胶原-血小板复合材料处理的前交叉韧带修复的结构特性将大于完整对侧前交叉韧带的20%。我们的目标是通过80%实现这一价值来实现。PI和研究人员拥有所需的专业知识和资源来评估这种有希望的新型设备，用于在已知的临床相关的犬膝前交叉韧带模型中进行创新的前交叉韧带修复。10只犬将接受单侧前交叉韧带修复，并接受临床评估(跛行和关节内病理)、关节松弛和愈合前交叉韧带修复的结构特性。对侧正常膝关节将作为对照，该研究小组先前完成的犬和猪的实验(前交叉韧带修复、重建和缺失)将作为历史对照。第一阶段的成功完成将由12周时完整修复、AP松弛、屈服载荷、跛行和半月板状态的先验标准来定义。与公共健康相关：每年进行超过300,000次前交叉韧带重建(ACLR)，估计美国卫生系统每年的成本为25亿美元。使用我们专有的胶原血小板复合体进行一期修复将显著减少手术时间和康复时间，消除与移植物收获相关的并发症和发病率，并保留天然前交叉韧带广泛的植入部位和本体感知功能，这将显著减少重建手术的痛苦和生产力损失。初步估计显示，使用我们的技术进行维修，可以为美国卫生系统节省超过10亿美元的直接成本，并通过恢复数千人-年的生产力，大大增加间接成本。