A Preclinical Model to Study the Influence of Graft Force on the Healing of the Anterior Cruciate Ligament Graft

Abstract

The purpose of this study is to establish a small animal anterior cruciate ligament (ACL) reconstruction research model where ACL graft force can be varied to create different graft force patterns with controlled knee motion. Cadaveric ( = 10) and in vivo ( = 10) rat knees underwent ACL resection followed by reconstruction using a soft tissue autograft. Five cadaveric and five in vivo knees received a nonisometric, high-force femoral graft tunnel position. Five cadaveric and five in vivo knees received a more isometric, low-force graft tunnel position. ACL graft force (N) was then recorded as the knee was ranged from extension to 90 degrees using a custom knee flexion device. Our results demonstrate that distinct ACL graft force patterns were generated for the high-force and low-force femoral graft tunnels. For high-force ACL grafts, ACL graft forces increased as the knee was flexed both in cadaveric and in vivo knees. At 90 degrees of knee flexion, high-force ACL grafts had significantly greater mean graft force when compared with baseline (cadaver: 7.76 ± 0.54 N at 90 degrees vs. 4.94 ± 0.14 N at 0 degree, = 0.004; in vivo: 7.29 ± 0.42 N at 90 degrees vs. 4.74 ± 0.13 N at 0 degree, = 0.007). In contrast, the graft forces for low-force ACL grafts did not change with knee flexion (cadaver: 4.94 ± 0.11 N at 90 degrees vs. 4.72 ± 0.14 N at 0 degree, = 0.41; in vivo: 4.78 ± 0.26 N at 90 degrees vs. 4.77 ± 0.06 N at 0 degree, = 1). Compared with nonisometric ACL grafts, the graft force for grafts placed in an isometric position had significantly lower ACL graft forces at 15, 30, 45, 60, 70, and 90 degrees in both cadaveric and in vivo knees. In conclusion, we have developed a novel ACL reconstruction model that can reproducibly produce two ACL graft force patterns. This model would permit further research on how ACL graft forces may affect subsequent graft healing, maturation, and function.

Small laboratory animal models of anterior cruciate ligament reconstruction

“…Mice have been recently used for ACL reconstruction studies, 71,72 and its inherent advantages relative to other small animal species include several transgenic species of mice that are available, which permits evaluation of impact of specific genes in healing after ACL reconstruction via knockout models. Based on its larger relatively larger size and associated technical advantages, rats have traditionally served as a more attractive rodent model with the Sprague–Dawley strain being the most popular 17,37,73,74 …”

“…The rat model has been particularly valuable for improving ACL reconstruction techniques by assessing the effects of tunnel location, ACL tendon graft pretension magnitude, and postoperative activity protocols on graft strain, tendon‐to‐bone integration, graft remodeling, and graft survival 17,18,37,75,101–103 . Similarly, murine models of ACL reconstruction have been used to study the tendon‐to‐bone formation and the impact of postoperative mechanical load on graft tunnel incorporation after ACL reconstruction 34,35 .…”

“…Due to a notable rate of failure and morbidity with ACL reconstruction, in vivo research that attempts to identify underlying reasons for failure or elucidating biological factors (i.e., cells or cellular mediators) and cellular mechanisms that may improve healing continue to be areas of research interest. Small animal laboratory species are not only used to model both noninvasive and invasive models of ACL injury, 11–15 but they are also commonly used to model ACL reconstruction to study healing and posttraumatic OA after ACL reconstruction 15–18 . Common small animal species used for laboratory research include mice, rats, guinea pigs, and rabbits 19–21 .…”

“…Small animal laboratory species are not only used to model both noninvasive and invasive models of ACL injury, [11][12][13][14][15] but they are also commonly used to model ACL reconstruction to study healing and posttraumatic OA after ACL reconstruction. [15][16][17][18] Common small animal species used for laboratory research include mice, rats, guinea pigs, and rabbits. [19][20][21] ACL injury models have been described in all four aforementioned small animal species; however, mice, rats, and rabbits are the most applicable small animal species for ACL reconstruction research.…”

The employment of cynomolgus monkey as proprioceptive deficit model of the anterior cruciate ligament

“…Therefore, the development of a proprioceptive deficit model of the ACL, which can simulate human ACL injury, is important for studying ACL moderate injury and help patients to restore their proprioception. A number of animal models have been established and used in previous studies, [13][14][15][16][17][18][19] but the majority are not suitable for related research. For example, certain small animals require less time to establish the model, but are associated with increased surgical and postoperative care due to the small body size, which can ultimately result in infection or death.…”