Enabling ACL Repair Using Proprietary Collagen Device

描述（由申请人提供）：研究人员在犬模型中开发并验证了胶原-血小板复合材料在生物力学和组织学上治疗部分ACL撕裂的效果。此外，血小板胶原蛋白装置已在猪模型中显示促进ACL修复。犬模型的改变有利于在已知的临床上相关的ACL损伤、修复、重建模型中评估我们的设备。该模型将用于评估骨关节炎（OA）的发展，验证步态/跛行评分，膝关节关节镜检查，将生物力学结果和组织学与已知标准进行比较，并有可能在未来控制康复。此外，避免了成年猪的巨大体型和“迷你猪”的供应和费用限制，从而降低了该装置的评估成本。PI在犬膝前交叉韧带重建、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前交叉韧带撕裂模型（使用我们的设备进行生物力学和组织学愈合）方面有着丰富的经验。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ACL修复的临床功能。假设1：在成功愈合后的4到12周内，跛行评分会下降，并且在安乐死时，内侧半月板撕裂和股骨内侧髁和胫骨内侧平台的软骨软化症较少。当80% <跛行率3时，我们的目标就达到了。目的2：描述胶原-血小板复合材料在愈合12周后对膝关节（前后位/轴位）松弛度的影响。假设2：经浓缩胶原-血小板复合物治疗的ACL修复膝关节，其AP松弛度值将在ACL重建术后的松弛度范围内（约为对侧完整膝关节的250%）。我们的目标是达到这个值的80%。目的3：测量12周后胶原-血小板复合材料修复的ACL的结构特性（最大载荷到失效/线性刚度）和组织学（细胞性/血管性）。假设3：胶原-血小板复合材料修复的ACL结构特性将大于对侧完整ACL的20%。我们的目标是达到这个值的80%。PI和研究人员拥有所需的专业知识和资源，可以在已知的临床相关犬膝关节ACL模型中评估这种有前途的新型设备，用于创新的ACL修复。10只犬将接受单侧前交叉韧带修复，并进行临床评估（跛行和关节内病理）、关节松弛度和愈合前交叉韧带修复的结构特性。对侧正常膝关节作为对照，该调查小组先前完成的犬和猪实验（ACL修复、重建和缺陷）作为历史对照。第一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来定义。公共卫生相关性：每年进行超过30万例ACL重建（ACLRs），估计美国卫生系统每年花费25亿美元。使用我们专有的胶原血小板复合材料进行初级修复，将大大缩短手术时间和康复时间，消除移植物收获相关的并发症和发病率，并保留原ACL的广泛插入位置和本体感觉功能，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，通过恢复数千人年的生产力损失，可以节省更多的间接成本。

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.