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（由申请方提供）：研究者在犬模型中开发并验证了胶原蛋白-血小板复合物，可在生物力学和组织学上治愈部分ACL撕裂。此外，血小板胶原装置已在猪模型中显示出促进ACL修复。犬模型的变更有利于在已知临床相关ACL损伤、修复、重建模型中评价我们的器械。该模型将允许评价骨关节炎（OA）的发展、经验证的步态/跛行评分、膝关节镜检查、生物力学结果和组织学与已知标准的比较，并有可能在未来控制康复。此外，避免了成年、生殖成熟的猪的巨大尺寸以及对“迷你猪”的供应和费用的限制，从而降低了该装置的评估成本。PI在犬膝关节ACL重建、半月板损伤模型、骨软骨同种异体移植和自体移植手术以及部分ACL撕裂模型（使用我们的器械进行生物力学和组织学愈合）方面具有丰富的经验。拟议的研究有以下目的。目的1：通过验证犬跛行评分评价胶原-血小板复合物ACL修复的临床功能。 假设1：跛行评分将在4 - 12周内降低，成功愈合，并与人道处死时内侧半月板撕裂和内侧股骨髁和内侧胫骨平台软骨软化较少相关。当80% <跛行3时，达到我们的目标。目的2：描述12周愈合后胶原-血小板复合物对膝关节松弛（前后/轴向）的影响。 假设二：用浓缩胶原-血小板复合物处理的ACL修复膝关节的AP松弛度值将在ACL重建后观察到的术后松弛度范围内（约为完整对侧膝关节的250%）。我们的目标是达到80%，实现这一价值。目标3：在12周后测量使用胶原-血小板复合物的愈合ACL修复的结构特性（最大失效载荷/线性刚度）和组织学（细胞构成/血管分布）。 假设三：用胶原-血小板复合物处理的ACL修复的结构特性将大于完整对侧ACL的20%。我们的目标是达到80%，实现这一价值。PI和研究者拥有所需的专业知识和资源，可在已知临床相关犬膝关节ACL模型中评价这种有前途的新型器械用于创新ACL修复。10只犬将接受单侧ACL修复，并进行临床评价（跛行和关节内病理学）、关节松弛和愈合ACL修复的结构特性。对侧正常膝关节将作为对照，该研究团队之前完成的犬和猪实验（ACL修复、重建和缺陷）将作为历史对照。第I阶段的成功完成将根据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进行定义。 公共卫生关系：每年进行超过300，000次ACL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材料进行一期修复将显著缩短手术时间和康复时间，消除与移植物采集相关的并发症和发病率，并保留原生ACL的广泛插入部位和本体感受功能，这将大大减少重建手术的疼痛和生产力损失。初步估计表明，使用我们的技术进行修复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损失来节省更多的间接成本。