Cook James L, Smith Patrick A, Stannard James P, Pfeiffer Ferris M, Kuroki Keiichi, Bozynski Chantelle C, Cook Cristi R
Department of Orthopaedic Surgery, University of Missouri, Columbia, Missouri.
Comparative Orthopaedic Laboratory, University of Missouri, Columbia, Missouri.
J Orthop Res. 2015 Aug;33(8):1171-9. doi: 10.1002/jor.22870. Epub 2015 Apr 6.
Development and validation of a large animal model for pre-clinical studies of intra-articular anterior cruciate ligament (ACL) reconstruction that addresses current limitations is highly desirable. The objective of the present study was to investigate a translational canine model for ACL reconstruction. With institutional approval, adult research hounds underwent arthroscopic debridement of the anteromedial bundle (AMB) of the ACL, and then either received a tendon autograft for "hybrid double-bundle" ACL reconstruction (n = 12) or no graft to remain ACL/AMB-deficient (n = 6). Contralateral knees were used as non-operated controls (n = 18) and matched canine cadaveric knees were used as biomechanical controls (n = 6). Dogs were assessed using functional, diagnostic imaging, gross, biomechanical, and histologic outcome measures required for pre-clinical animal models. The data suggest that this canine model was able to overcome the major limitations of large animal models used for translational research in ACL reconstruction and closely follow clinical aspects of human ACL reconstruction. The "hybrid double-bundle" ACL reconstruction allowed for sustained knee function without the development of osteoarthritis and for significantly improved functional, diagnostic imaging, gross, biomechanical, and histologic outcomes in grafted knees compared to ACL/AMB-deficient knees.
开发并验证一种用于关节内前交叉韧带(ACL)重建临床前研究的大型动物模型,以解决当前的局限性,这是非常必要的。本研究的目的是研究一种用于ACL重建的转化犬模型。经机构批准,成年实验猎犬接受了ACL前内侧束(AMB)的关节镜清创术,然后一部分接受自体肌腱移植进行“混合双束”ACL重建(n = 12),另一部分不进行移植,保持ACL/AMB缺损状态(n = 6)。对侧膝关节用作非手术对照(n = 18),匹配的犬类尸体膝关节用作生物力学对照(n = 6)。使用临床前动物模型所需的功能、诊断成像、大体、生物力学和组织学结果测量指标对犬进行评估。数据表明,该犬模型能够克服用于ACL重建转化研究的大型动物模型的主要局限性,并密切跟踪人类ACL重建的临床情况。与ACL/AMB缺损的膝关节相比,“混合双束”ACL重建可使膝关节功能持续,不发生骨关节炎,并且移植膝关节的功能、诊断成像、大体、生物力学和组织学结果得到显著改善。