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Orthopedic and Rehabilitation Engineering

A Non-Invasive Compressive Loading Injury Model for Anterior Cruciate LigamentRupture in Rodents

(L-454) A Non-Invasive Compressive Loading Injury Model for Anterior Cruciate Ligament Rupture in Rodents

Friday, October 13, 2023

9:30 AM – 10:30 AM PDT

Location: Exhibit Hall - Row L - Poster # 454

Presenting Author(s)

Jake Heinonen

Research Assistant
University of Oregon
West Linn, Oregon, United States

Co-Author(s)

NP

Nicholas Pancheri

PhD Student
University of Oregon, United States
SR

Sruthi Ranganathan

PhD Student
University of Oregon, United States
SK

Salil Karipott

Postdoctoral Scholar
University of Oregon, United States
AL

Angela Lin

Senior Research Engineer
University of Oregon, United States

Primary Investigator(s)

RG

Robert Guldberg

Executive Director
University of Oregon, Knight Campus for Accelerating Scientific Impact, United States

Introduction:: Osteoarthritis (OA) is a debilitating condition characterized by wearing down of articular cartilage in joints. OA affects millions of people annually, with a minority of cases considered post-traumatic osteoarthritis (PTOA), or arising following injury to the joint. The early onset of PTOA affects younger and more active individuals, which can be associated with early joint replacements, longer durations of reduced quality of life, and billions of dollars in annual costs in the United States. Novel therapies to stop/reverse OA progression are desirable, and one way to assess the efficacy of these novel drugs is with preclinical animal models. PTOA in rodents has commonly been studied using surgical models that destabilize the joint, such as a medial meniscal transection (MMT) surgical model. However, surgical models may fail to fully recapitulate how a joint injury will progress to OA in humans. Surgical approaches lead to inflammatory responses in the joint that may confound the effects of the PTOA disease state. Therefore, there has been increasing interest in developing non-invasive PTOA models that use compressive loads to destabilize the joint. The goals of this project were to produce a portable system that could reproducibly rupture the rat ACL without damage to other ligaments and to measure the ranges of force necessary to rupture the ACL in this model.

Materials and Methods::

A compressive loading apparatus was developed based upon previous literature and consultation with those authors. A ball-bearing hydraulic piston was combined with a custom circuit board regulated via voltage-pressure monitor. An established Labview control system was utilized, where voltage is controlled by the user and through a voltage-pressure regulator to control hydraulic pressure. The hydraulic piston was mated to a custom aluminum chassis (Figure 1). Force was measured with a TLL series 2224.11N capacity load cell. Measured voltages were calibrated to force readings via spring constants/Hooke’s law and a previously validated load cell.

Preliminary testing was performed on cadaveric animals (N=2), and an animal euthanized directly after testing (N=1). Joint laxity and range of motion were physically assessed before and after injury. A 5N preload was applied and held for 30 seconds, and force was ramped up by 2.5 N/s until rupture occurred, as detected by abrupt translation of the tibia. After euthanization, knees were microdissected to assess the joint status and ACL condition.

Results, Conclusions, and Discussions::

Results: Full-thickness ACL rupture (verified via careful microdissections) was achieved in all cases and occurred in the proximal third of the ACL at 55 +/- 10N. No damage to the tibia, femur, or patella occurred, as confirmed by Faxitron X-ray (Figure 2). Destabilization of the joint following injury was qualitatively physically evaluated as an increase in joint laxity (movement in sagittal, coronal, transverse directions) and internal/external rotation. Upon dissection to further verify joint status, no apparent damage was observed to other surrounding ligaments, and the ACLs were verified as ruptured in all cases with no evidence of bony avulsion. Moderate contusion of muscle tissue and infrapatellar fat pad (IFP) was observed.

Conclusions: As a result of this project, we have built, calibrated, and validated a device for applying a non-invasive compressive load to produce ACL rupture in all subjects in this pilot consistently. There were no observed concomitant injuries to the bones or other ligaments surrounding the ACL, demonstrating that the goal of solely rupturing the ACL without damage to other structural components of the knee was achieved. At the specified loading rate, the range of force required for ACL rupture to occur for all animals was found to be 55+/-10N.

Discussions: This work demonstrated the feasibility of building and validating a low-cost, portable device for producing ACL rupture in a preclinical rodent model. Current studies in our lab are characterizing the structural, pain, and mobility changes associated with the non-invasive ACL rupture model with the aim of utilizing the method for future treatment efficacy studies.

Acknowledgements (Optional): :

This work was funded by the Wu Tsai Human Performance Alliance at Oregon. Authors would also like to thank past and present members of the Sharma lab at University of Florida for providing insight, drawings, Labview code, and discussion around building the NIKI device.

References (Optional): :