Regenerative Engineering Animal Models for Knee Osteoarthritis

Abstract

Osteoarthritis (OA) of the knee is the most common synovial joint disorder worldwide, with a growing incidence due to increasing rates of obesity and an aging population. A significant amount of research is currently being conducted to further our understanding of the pathophysiology of knee osteoarthritis to design less invasive and more effective treatment options once conservative management has failed. Regenerative engineering techniques have shown promising preclinical results in treating OA due to their innovative approaches and have emerged as a popular area of study. To investigate these therapeutics, animal models of OA have been used in preclinical trials. There are various mechanisms by which OA can be induced in the knee/stifle of animals that are classified by the etiology of the OA that they are designed to recapitulate. Thus, it is essential to utilize the correct animal model in studies that are investigating regenerative engineering techniques for proper translation of efficacy into clinical trials. This review discusses the various animal models of OA that may be used in preclinical regenerative engineering trials and the corresponding classification system.

Keywords: Animal models; Osteoarthritis; Preclinical trials; Regenerative engineering; Translation.

Fig. 1

Comparison of normal (A) and osteoarthritic (B) joints. A Normal synovial joint and structures. B The signaling pathways and structural changes that occur as osteoarthritis develops within a diseased joint. ADAMTS, a disintegrin and metalloproteinase with thrombospondin-like motifs; IL, interleukin; MMP, matrix metalloproteinase; TNF, tumor necrosis factor; IFN, interferon; IGF, insulin-like growth factor; TGF, transforming growth factor; VEGF, vascular endothelial growth factor (Glyn-Jones et al. [12])

Fig. 2

Proposed classification of OA animal models in vivo. ACL, anterior cruciate ligament; PCL, posterior cruciate ligament; MMTL, medial meniscotibial ligament

Fig. 3

Gross images of a rabbit knee before (A) and after (B) transection of the ACL. A The black arrow indicates intact ACL. B The white arrow indicates the transected ACL (Lozano et al [55])

Fig. 4

Schematic overview of changes in the ACLT-Meniscectomy model. Altered biomechanics due to post-surgical changes produces cartilage damage in both the medial and lateral compartments, but more severe osteoarthritic changes are noted on the medial compartment where the medial meniscus was removed. In the medial compartment, thinning and increased porosity of the subchondral plate are noted along with cartilage degeneration (inset). In the lateral compartment, trabecular bone decreases (−) indicating unloading either due to total paw unloading or locally due to the varus angle (arrows). Trabecular changes are not noted in the medial compartment (=/−) where the medial meniscus was removed (Intema et al. [58])

Fig. 5

C-arm radiograph of a guided injection of intra-articular collagenase in the knee joint of a mouse to induce osteoarthritic changes. Collagenase is encapsulated within the joint space

Fig. 6

Dynamic/noninvasive model of OA: transarticular impact. A mass of 2000N with a padded interface is dropped onto the flexed patellofemoral joint to produce intra-articular changes within the knee joint (Ewers et al. [87])