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Previous studies have shown that reconstructive surgery alone following injury to the anterior cruciate ligament (ACL) does not prevent the development of post-traumatic osteoarthritis (PTOA). Poloxamer 188 (P188) has been shown to prevent cell death following trauma in both articular cartilage and meniscal tissue. This study aims to test the efficacy of single or multiple administrations of P188 in conjunction with reconstructive surgery to help prevent or delay the onset of the disease. Thirty skeletally mature rabbits underwent closed-joint trauma that resulted in ACL rupture and meniscal damage and were randomly assigned to one of four treatment groups with varying doses of P188. ACL reconstruction was then performed using an autograft from the semitendinosus tendon. Animals were euthanized 1-month following trauma, meniscal tissue was assessed for changes in morphology, mechanical properties, and proteoglycan content. Femurs and tibias were scanned using microcomputed tomography to determine changes in bone quality, architecture, and osteophyte formation. The medial meniscus experienced more damage and a decrease in the instantaneous modulus regardless of treatment group, while P188 treatment tended to limit degenerative changes in the lateral meniscus. Both lateral and medial menisci had documented decreases in the equilibrium modulus and inconsistent changes in proteoglycan content. Minimal changes were documented in the tibias and femurs, with the only significant change being the formation of osteophytes in both bones regardless of treatment group. The data suggest that P188 was able to limit some degenerative changes in the meniscus associated with PTOA and may warrant future studies., (Copyright © 2022 by ASME.)

Objective: The objective of this study was to monitor the progression of joint damage in two animal models of knee joint trauma using two non-invasive, clinically available imaging modalities., Methods: A 3-T clinical magnet and micro-computed tomography (μCT) was used to document changes immediately following injury (acute) and post-injury (chronic) at time points of 4, 8, or 12 weeks. Joint damage was recorded at dissection and compared to the chronic magnetic resonance imaging (MRI) record. Fifteen Flemish Giant rabbits were subjected to a single tibiofemoral compressive impact (ACLF), and 18 underwent a combination of anterior cruciate ligament (ACL) and meniscal transection (mACLT)., Results: All ACLF animals experienced ACL rupture, and 13 also experienced acute meniscal damage. All ACLF and mACLT animals showed meniscal and articular cartilage damages at dissection. Meniscal damage was documented as early as 4 weeks and worsened in 87% of the ACLF animals and 71% of the mACLT animals. Acute cartilage damage also developed further and increased in occurrence with time in both models. A progressive decrease in bone quantity and quality was documented in both models. The MRI data closely aligned with dissection notes suggesting this clinical tool may be a non-invasive method for documenting joint damage in lapine models of knee joint trauma., Conclusions: The study investigates the acute to chronic progression of meniscal and cartilage damage at various time points, and chronic changes to the underlying bone in two models of posttraumatic osteoarthritis (PTOA), and highlights the dependency of the model on the location, type, and progression of damage over time., (Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Purpose: To further elucidate the direct and indirect fibre insertion morphology within the human ACL femoral attachment using scanning electron microscopy and determine where in the footprint each fibre type predominates. The hypothesis was that direct fibre attachment would be found centrally in the insertion site, while indirect fibre attachment would be found posteriorly adjacent to the posterior articular cartilage., Methods: Ten cadaveric knees were dissected to preserve and isolate the entirety of the femoral insertion of the ACL. Specimens were then prepared and evaluated with scanning electron microscopy to determine insertional fibre morphology and location., Results: The entirety of the fan-like projection of the ACL attachment site lay posterior to the lateral intercondylar ridge. In all specimens, a four-phase architecture, consistent with previous descriptions of direct fibres, was found in the centre of the femoral attachment site. The posterior margin of the ACL attachment attached directly adjacent to the posterior articular cartilage with some fibres coursing into it. The posterior portion of the ACL insertion had a two-phase insertion, consistent with previous descriptions of indirect fibres. The transition from the ligament fibres to bone had less interdigitations, and the interdigitations were significantly smaller (p < 0.001) compared to the transition in the direct fibre area. The interdigitations of the direct fibres were 387 ± 81 μm (range 282-515 μm) wide, while the interdigitations of indirect fibres measured 228 ± 75 μm (range 89-331 μm)., Conclusions: The centre of the ACL femoral attachment consisted of a direct fibre structure, while the posterior portion had an indirect fibre structure. These results support previous animal studies reporting that the centre of the ACL femoral insertion was comprised of the strongest reported fibre type. Clinically, the femoral ACL reconstruction tunnel should be oriented to cover the entirety of the central direct ACL fibres and may need to be customized based on graft type and the fixation device used during surgery.

Healthy menisci function within the joint to prevent the underlying articular cartilage from excessive loads. Understanding how mechanical properties of menisci change with degeneration can drive future therapeutic studies to prevent this degeneration. Thus, the goal of this study was to characterize both compressive and tensile moduli of human menisci with varying degrees of gross damage due to osteoarthritis (OA). Twenty four paired menisci were collected from total knee joint replacement patients and the menisci were graded on a scale from 0-4 according to level of gross meniscal degeneration with 0=normal and 4=full tissue maceration. Each meniscus was then sectioned into anterior and posterior regions and subjected to indentation relaxation tests. Samples were sliced into 1mm thick strips, made into dumbbells using a custom punch, and pulled to failure. Significant decreases in instantaneous compressive modulus were seen in the lateral posterior region between grades 0 and 1 (36% decrease) and in the medial anterior regions between grades 1 and 2 (67% decrease) and 1 and 3 (72% decrease). Changes in equilibrium modulus where seen in the lateral anterior region between grades 1 and 2 (35% decrease), lateral posterior region between grades 0-2 (41% decrease), and medial anterior regions between grades 1 and 2 (59% decrease), 1 and 3 (67% decrease), 2 and 4 (54% decrease), and 3 and 4 (42% decrease). No significant changes were observed in tensile modulus across all regions and degenerative grades. The results of this study demonstrate the compressive moduli are affected even in early stages of gross degeneration, and continue to decrease with increased deterioration. However, osteoarthritic menisci retain a tensile modulus similar to that of previously reported healthy menisci. This study highlights progressive changes in meniscal mechanical compressive integrity as level of gross tissue degradation increases, and thus, early interventions should focus on restoring or preserving compressive integrity., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The objective of this study was to induce anterior cruciate ligament (ACL) and meniscal damage, via a single tibiofemoral compressive impact, in order to document articular cartilage and meniscal changes post-impact. Tibiofemoral joints of Flemish Giant rabbits were subjected to a single blunt impact that ruptured the ACL and produced acute meniscal damage. Animals were allowed unrestricted cage activity for 12 weeks before euthanasia. India ink analysis of the articular cartilage revealed higher degrees of surface damage on the impacted tibias (p=0.018) and femurs (p<0.0001) compared to controls. Chronic meniscal damage was most prevalent in the medial central and medial posterior regions. Mechanical tests revealed an overall 19.4% increase in tibial plateau cartilage thickness (p=0.026), 34.8% increase in tibial plateau permeability (p=0.054), 40.8% increase in femoral condyle permeability (p=0.029), and 20.1% decrease in femoral condyle matrix modulus (p=0.012) in impacted joints compared to controls. Both instantaneous and equilibrium moduli of the lateral and medial menisci were decreased compared to control (p<0.02). Histological analyses revealed significantly increased presence of fissures in the medial femur (p=0.036). In both meniscus and cartilage there was a significant decrease in GAG coverage for the impacted limbs. Based on these results it is clear that an unattended combined meniscal and ACL injury results in significant changes to the soft tissues in this experimental joint 12 weeks post-injury. Such changes are consistent with a clinical description of mid to late stage PTOA of the knee., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The menisci have crucial weight-bearing roles in the knee. Regional variations in structure and cellularity of the meniscus have only been minimally investigated. Therefore, the goal of this study was to illustrate the regional cell density, tissue area, and structure of healthy lapine menisci. Skeletally mature Flemish Giant rabbits were used for this study. Upon sacrifice, menisci were removed, fixed in formalin, and cryosectioned. Histological analysis was performed for the detection of sulfated glycosaminoglycans (GAG), collagen Types I and II, cellular density, and tissue area. ANOVA and paired t tests were used for testing of statistical significance. Glycosaminoglycan coverage of the medial meniscus significantly varied between regions, with the anterior region demonstrating significantly more GAG coverage than the posterior region. Inter- and intra-meniscal comparisons revealed variations between zones, with trends that outer zones of the medial menisci had less GAG coverage. Collagen Types I and II had marked characteristics and varying degrees of coverage across regions. Tissue area varied between regions for both medial and lateral menisci. Cellular density was dependent on region in the lateral meniscus. This is the first study to illustrate regional and zonal variation in glycosaminoglycan coverage, size, and cellular density for healthy lapine meniscal tissue. This data provides baseline information for future investigations in meniscal injury models in rabbits.

A computational model of the tibiofemoral joint utilizing the discrete element analysis method has been developed and validated with human cadaveric knees. The computational method can predict load distributions to within a root mean square error (RMSE) of 3.6%. The model incorporates subject-specific joint geometry and the health of the subjects' articular cartilage to determine the cartilage stiffness. It also includes the collateral and cruciate ligaments and utilizes stiffness values derived from literature for these elements. Comparisons of the total load, peak load, and peak load location for axial, varus, and valgus loading conditions confirmed that there was less than 4% RMSE between the analytical and experimental results. The model presented in this paper can generate results with minimal computational time and it can be used as a non-invasive method for characterizing and monitoring subject-specific knee loading patterns.