A novel large animal model of posttraumatic osteoarthritis induced by inflammation with mechanical stability.

OBJECTIVES: Animal models are needed to reliably separate the effects of mechanical joint instability and inflammation on posttraumatic osteoarthritis (PTOA) pathogenesis. We hypothesized that our modified intra-articular drilling (mIAD) procedure induces cartilage damage and synovial changes through increased inflammation without causing changes in gait. METHODS: Twenty-four Yucatan minipigs were randomized into the mIAD (n=12) or sham control group (n=12). mIAD animals had two osseous tunnels drilled into each of the tibia and femur adjacent to the anterior cruciate ligament (ACL) attachment sites on the left hind knee. Surgical and contralateral limbs were harvested 15 weeks post-surgery. Cartilage degeneration was evaluated macroscopically and histologically. Synovial changes were evaluated histologically. Interleukin-1 beta (IL-1ß), nuclear factor kappa B (NF-κB), and tumor necrosis factor alpha (TNF-α) mRNA expression levels in the synovial membrane were measured using quantitative real-time polymerase chain reaction. IL-1ß and NF-κB levels in chondrocytes were assessed using immunohistochemistry. Load asymmetry during gait was recorded by a pressure-sensing walkway system before and after surgery. RESULTS: The mIAD surgical knees demonstrated greater gross and histological cartilage damage than contralateral (P<.01) and sham knees (P<.05). Synovitis was present only in the mIAD surgical knee. Synovial inflammatory marker (IL-1ß, NF-κB, and TNF-α) expression was three times higher in the mIAD surgical knee than the contralateral (P<.05). Chondrocyte IL-1ß and NF-κB levels were highest in the mIAD surgical knee. In general, there were no significant changes in gait. CONCLUSIONS: The mIAD model induced PTOA through inflammation without affecting gait mechanics. This large animal model has significant applications for evaluating the role of inflammation in PTOA and for developing therapies aimed at reducing inflammation following joint injury.

Hydrogel treatment for idiopathic osteoarthritis in a Dunkin Hartley Guinea pig model.

The study objective was to determine if intraarticular injections of an extracellular matrix (ECM) powder and blood composite (ECM-B) would have a significant impact on post-operative gait parameters without eliciting adverse cartilage changes or severe lymphatic reactions in an idiopathic osteoarthritis (OA) model. Twenty-one Dunkin Hartley Guinea pigs received an intraarticular injection of ECM-B in each knee and were split into sub-groups for gait assessment and post-harvest knee evaluations at 1 week (n = 5), 2 weeks (n = 5), 4 weeks (n = 5), or 8 weeks (n = 6). The results were compared with a control group (n = 5), which underwent bilateral injections of phosphate-buffered saline (PBS), gait measurements at 1, 2, 4, and 8 weeks, and post-mortem knee evaluation at 8 weeks post-injection. Hind limbs and popliteal lymph nodes were collected at the Week 8 endpoint and underwent histological analysis by a veterinary pathologist. Significant improvement in hind limb base of support was observed in the ECM-B group compared to the control group at Week 4 but was no longer significant by Week 8. No significant differences were observed between control and ECM-B groups in hind limb cartilage, synovium, or popliteal lymph node histology at Week 8. In conclusion, administration of an ECM-B material may improve gait for a limited time without significant adverse effects on the cartilage, synovium, or local lymph nodes.

Effects of Male and Female Sex on the Development of Posttraumatic Osteoarthritis in the Porcine Knee After Anterior Cruciate Ligament Surgery.

BACKGROUND: Posttraumatic osteoarthritis (PTOA) is a common sequela of anterior cruciate ligament (ACL) injury, even when surgical treatment is selected. The effect of patient sex on cartilage health after ACL injury and surgical treatment has been less studied. PURPOSE/HYPOTHESIS: The study objective was to compare the macroscopic cartilage damage that develops after ACL surgery in male and female Yucatan minipigs. It was hypothesized that after ACL surgery, the macroscopic cartilage damage of the tibiofemoral joints from female animals would be greater than that from male animals. Additionally, it was hypothesized that the effect of sex on the macroscopic cartilage damage would depend on surgical treatment. STUDY DESIGN: Controlled laboratory study. METHODS: Twelve-month follow-up data were obtained for 55 adolescent Yucatan minipigs (22 female/33 male) that were randomized to 1 of 3 experimental groups: no treatment (ACL transection [ACLT]), ACL reconstruction, and bridge-enhanced ACL restoration. The Osteoarthritis Research Society International guidelines were used to determine a standardized macroscopic cartilage damage score on 5 surfaces of the knee joint. RESULTS: Females had significantly worse mean total macroscopic cartilage damage scores on the surgical side (adjusted P value [P adj] = .04) and significantly better scores on the contralateral side (P adj = .01) when compared with males. The trochlear damage scores were also significantly worse in females for surgical limbs (P adj = .009) and significantly better for the contralateral limbs (P adj < .001) when compared with males. Although there were no significant differences in total macroscopic cartilage damage scores between sexes within treatment groups on the surgical limbs (ACLT, P adj = 0.45; ACL reconstruction, P adj = .56; bridge-enhanced ACL restoration, P adj = .23), the mean trochlear scores on the surgical limb of females were significantly worse than those of the males in the ACLT group (P adj = .003). CONCLUSION: Mean total macroscopic cartilage damage scores of Yucatan minipigs were significantly worse in females than males, regardless of treatment. These differences were predominantly found in the trochlear scores across all treatment groups. CLINICAL RELEVANCE: These data suggest that patient sex could be more influential in the progression of PTOA than surgical treatment after ACL injury. Identifying factors responsible for this discrepancy may prove valuable to identify targets to slow PTOA progression in male and female ACL-injured populations.