Assessment of osteoarthritis functional outcomes and intra‐articular injection volume in the rat anterior cruciate ligament transection model

Abstract

The rat surgical anterior cruciate ligament transection (ACLT) model is commonly used to investigate intra‐articular osteoarthritis (OA) therapies, and histological assessment is often the primary outcome measure. However, histological changes do not always correlate well with clinical outcomes. Therefore, this study evaluated functional outcomes in the rat surgical ACLT model and compared intra‐articular injection volumes ranging from 20 to 50 μl. Unilateral ACLT was surgically induced and static weight‐bearing, mechanical allodynia, motor function, and gait were assessed in four groups of male, Sprague‐Dawley rats (n = 6 per group). Intra‐articular injections of 20 µl Dulbecco's phosphate‐buffered saline (DPBS), 50 µl DPBS, or 50 µl of synthetic biomimetic boundary lubricant were administered once weekly for 3 weeks postoperatively. Structural changes were evaluated histologically at 20 weeks. Rat cadaver knees were injected with 20, 30, 40, or 50 µl of gadolinium solutions and were imaged using magnetic resonance imaging (MRI). Static weight‐bearing, mechanical allodynia, and gait parameters in ACLT groups revealed differences from baseline and naïve controls for 4 weeks post‐ACLT; however, these differences did not persist beyond 6 weeks. Different intra‐articular DPBS injection volumes did not result in functional or histological changes; however, peri‐articular leakage was documented via MRI following 50, 40, and 30 µl but not 20 µl gadolinium injections. Statement of clinical significance: Differences in functional parameters were predominantly restricted to early, postoperative changes in the rat surgical ACLT model despite evidence of moderate histologic OA at 20 weeks. Injection volumes of 20–30 µl are more appropriate for investigating intra‐articular therapies in the rat knee.

Impact of arthroscopy on post‐procedure intra‐articular elbow injections: A cadaveric study

“…The results of this study indicate that larger 3D volumes and extravasation scores were noted in elbows with an IA injection of 4 mL, compared to 2 mL of contrast, regardless of whether they underwent arthroscopy. Both treatment groups that received an IA injection of 2 mL of contrast had a lower mean extravasation score of 1.55, indicating that less than 25% extravasation was noted in most elbows, which is categorized as minor similar to previous studies by Sutherland et al and Wang et al 30,31 The cadaveric study by Wang et al investigating IA injections in rat stifles also concluded that larger volumes resulted in more extravasation 31 . All post‐contrast 3D volumes were larger than the pre‐contrast 3D volumes.…”

“…The post‐contrast images were assessed for the presence of contrast within the joint, filling defects characterized by a lack of contrast present in region(s) of the joint, and the presence of contrast extravasation. Contrast extravasation on radiographs and CT images was scored by the radiologist on a scale from 0 to 4 (0 = no extravasation, 1 = < 25% contrast extravasation outside the joint, 2 = 25%–50% contrast extravasation outside the joint, 3 = 50%–75% contrast extravasation outside the joint, 4 = >75% contrast extravasation outside the joint) 30,31 …”

Axial Compressive Loading Attenuates Early Osteoarthritis by Reducing Subchondral Bone Remodeling

“…47 ACL transection resulted in impaired locomotion, mechanical allodynia, and mechanical loading loss in the early phase in animal studies. 40,46 ACLT and sham surgery decreased the weightbearing and increased the number of TRAP-positive osteoclasts in the subchondral bone as early as 1 week. 43 The activation of osteoclasts promoted proinflammatory cytokines and proteases, contributing to cartilage damage.…”

Effects of a Combination of Polynucleotide and Hyaluronic Acid for Treating Osteoarthritis

“…The OA model, induced by ACLT and MMx, involved the transection of both the anterior cruciate ligament and patellar tendon [44,58,59]. MMx was performed as previously described [60].…”