Small laboratory animal models of anterior cruciate ligament reconstruction

Abstract

Anterior cruciate ligament (ACL) injuries are common knee ligament injuries. While generally successful, ACL reconstruction that uses a tendon graft to stabilize the knee is still associated with a notable percentage of failures and long‐term morbidities. Preclinical research that uses small laboratory species (i.e., mice, rats, and rabbits) to model ACL reconstruction are important to evaluate factors that can impact graft incorporation or posttraumatic osteoarthritis after ACL reconstruction. Small animal ACL reconstruction models are also used for proof‐of‐concept studies for the development of emerging biological strategies aimed at improving ACL reconstruction healing. The objective of this review is to provide an overview on the use of common small animal laboratory species to model ACL reconstruction. The review includes a discussion on comparative knee anatomy, technical considerations including types of tendon grafts employed amongst the small laboratory species (i.e., mice, rats, and rabbits), and common laboratory evaluative methods used to study healing and outcomes after ACL reconstruction in small laboratory animals. The review will also highlight common research questions addressed with small animal models of ACL reconstruction.

Repair potential of self‐assembling peptide hydrogel in a mouse model of anterior cruciate ligament reconstruction

“…In this study, while 0.4 mm bone tunnels were created in mice, ACLR in humans involves creating bone tunnels of sizes ranging from 7.5–10 mm [ 36 ], indicating a significant difference in size. Additionally, it is believed that there are significant differences in the process of tendon remodelling and incorporation between mice and humans [ 4 ]. Although in our mouse model we, like many researchers, considered 4 weeks as the endpoint of treatment, in actual clinical practice, a treatment period over 6 months is required [ 4 , 27 ].…”

“…Additionally, it is believed that there are significant differences in the process of tendon remodelling and incorporation between mice and humans [ 4 ]. Although in our mouse model we, like many researchers, considered 4 weeks as the endpoint of treatment, in actual clinical practice, a treatment period over 6 months is required [ 4 , 27 ]. Therefore, there is a possibility that the results of this study may not directly translate to clinical practice.…”

Preclinical tendon and ligament models: Beyond the 3Rs (replacement, reduction, and refinement) to 5W1H (why, who, what, where, when, how)

“…Some rodent ACL studies focus on growth and development, as well as homeostasis, to investigate mechanisms by which this specialized tissue is formed and maintained 9,17 . Additionally, injury models exist where an injury is induced either through surgical transection or nonsurgical rupture and then either reconstructed 14,15,18–23 or left to heal naturally 24–27 .…”

“…Some rodent ACL studies focus on growth and development, as well as homeostasis, to investigate mechanisms by which this specialized tissue is formed and maintained. 9,17 Additionally, injury models exist where an injury is induced either through surgical transection or nonsurgical rupture and then either reconstructed 14,15,[18][19][20][21][22][23] or left to heal naturally. [24][25][26][27] Given the role of the ACL as a primary restraint to anterior tibial translation, these models to destabilize the knee in both rats and mice are also commonly used to study posttraumatic osteoarthritis.…”

A Comprehensive Model of Blood Flow Restriction in the Post-surgical Rat

“…BFR-exercise is used to attenuate muscle loss following common orthopedic surgeries, including ACL-R surgery in humans 4,6,39 . Rat models of ACL-R have been previously described to explore technical modifications and to trial engineered allografts of the ACL for ACL-R [40][41][42][43][44] . ACL-R as a model of post-surgical muscle loss for BFR-exercise in rats has not been extensively described but offers a clinically relevant foundation to study the hypertrophic effects of BR-exercise in rats.…”