Introduction and Aim

Quadriceps strength is crucial for physical function in patients with knee osteoarthritis (KOA). This study aimed to investigate the effect of combining blood flow restriction (BFR) with low-intensity training (LIT) on quadricep strength in patients with advanced KOA.

Highly crosslinked polyethylene (HXLPE) has been used with great clinical success in total hip arthroplasty (THA) since its debut in the late 1990's. However, reports regarding this bearing couple in its second decade of service are still scant. The aim of this study was to 1. Determine the long term clinical and radiological results and 2. Investigate what factors affect wear rates using a metal-on-HXLPE bearing articulation.

55 THA's using a single brand of HXLPE liner, cementless cup and 28mm hip ball were performed in 44 patients. Age, sex, and Charlson Comorbidity Index (CCI) and need for revision surgery were recorded. Linear and volumetric wear was determined using the Martell method.

Mean age at operation was 51.2 (29–73 +/− 12.1) years. Mean duration of follow up was 16.9 years (range 15.0–20.1 +/− 1.1 years). Osteolysis was not present in the latest follow up radiographs.

Median linear and volumetric wear rate was 0.035mm/year (95% CI 0.031–0.047) and 7.12mm³/year (95% CI 6.92–17.25) respectively. Acetabular component position was not found to be related to both linear and volumetric wear. No significant difference was found in the linear and volumetric wear rates of thinner and thicker liners (8mm or below and > 8mm) (p=0.827 and p=0.843 respectively).

HXLPE is associated with very low linear and volumetric wear rates which has virtually obviated osteolysis and has translated to excellent survivorship even at long term follow up. In-vivo oxidation does not appear to be of clinical concern at this point in its service cycle.

The meniscus is at the cornerstone of knee joint function, imparting stability and ensuring shock absorption, load transmission, and stress distribution within the knee joint. However, it is very vulnerable to injury and age-related degeneration. Meniscal tears are reported as the most common pathology of the knee with a mean annual incidence of 66 per 100,000. Knee osteoarthritis progresses more rapidly in the absence of a functional meniscus. Historically, tears extending to the avascular inner portion of the meniscus (white-white zone, “WW”), such as radial tears were considered as untreatable and were often resected, due to the lack of vascularity in the WW zone. Perfusion-based anatomical studies performed on cadaveric menisci in the 1980s shaped the current dogma that human meniscus has poor regenerative capacity, partly due to limited blood supply that only reaches 10 to 25% of the meniscus, commonly referred to as red-red zone (“RR”). Previous studies, including those utilizing animal models have shown mobilization of Mesenchymal Stem Cells (MSCs) upon injury into the WW zone, and successful MSC recruitment when administered externally to the injury site. We and others have recently reported positive outcomes of repaired tears in the inner zone of patients. We hypothesized that the “avascular” white-white zone of the meniscus possesses regenerative capacity due to a resident stem/progenitor cell population. Further, we sought to redefine the presence of microvessels in all meniscal zones using advanced stereology and imaging modalities.

Fifteen menisci from fresh human cadaveric knees (mean age: 21.53±6.53 years) without evidence of previous injury were obtained from two tissue banks (JRF, Centennial, CO) and Biosource Medical (Lakeland, FL) and utilized for this study. The use of cadaveric specimens for research purposes was approved by the institutional review board. Tibial plateaus were dissected to harvest medial and lateral menisci along their entire length. The RR, red-white (RW) and WW zones were dissected and separated into three thirds from the inner aspect to the marginal border of the meniscus and their wet weights recorded (Fig.1A). Meniscus tissue cellular content in each zone was obtained from dissociation of meniscus tissue using 0.02% w/v pronase (Millipore) for 1h at 37oC, followed by 18h 0.02% w/v collagenase II (Worthington) at 37oC with shaking. Isolated cells were characterized immediately after harvest using flow cytometry with antibodies against MSCs surface markers (CD105, CD90, CD44 and CD29) as well as respective isotype controls. Further, meniscal cells were cultured and split twice when confluence was reached, characterized at P2 and compared to bone marrow-derived MSCs (BM-MSCs) using the same markers. Self-renewal of cells was assessed using colony forming unit (CFU) assay. Differentiation assays were performed to assess whether colony-forming cells retained multilineage potential. For morphological examination of bigger vessels, samples were fixed in 10% formalin for 1 week, paraffin embedded, sectioned (4 μm thick) and stained with H&E and Masson's trichrome. Presence of microvessels was assessed by CD31 immunofluorescence staining. Further, menisci were cleared using the uDisco protocol labeled with the TO-PRO®-3 stain, a fluorescent dye that stains cell nuclei and imaged using light-sheet microscopy. All continuous data are presented as mean ±standard deviation. Non-repeated measures analysis of variance (ANOVA) and Tukey-Kramer HSD post hoc analysis were performed on sample means for continuous variables. Statistical significance was set at p < 0 .05.

Menisci were successfully cleared using a modified uDISCO procedure, imaged and analyzed for total cell density. As expected, bigger vessels were observed in RR but not in WW. However, immunofluorescent staining for CD31 showed a subset of CD31+endothelial cells present in the WW zone, indicating the presence of small vessels, most likely capillaries. In order to assess whether enzymatic digestion had a differential result depending on meniscus zone due to cellular content, we analyzed yields per meniscus per zone. The wet weight of different zones (WW:RW:RR) was at a ratio of ∼1:3:5 respectively, however, the ratio of cells isolated from each zone was at ∼1:4:20, indicating that RR has a denser population of mononuclear cells. However, the difference between all zones in cell yields was not significant. The clonogenic potential of isolated cells was shown to be non-significantly different between the three zones. Differentiation of isolated cells to osteogenic lineage using osteogenic media in vitroshowed no difference between the three zones. Flow cytometry analysis of cells from the three meniscal zones displayed presence of two distinct subpopulations of cells immediately after isolation. One subpopulation was positive to MSC surface markers and the other negative. Additionally, flow cytometry of cultured meniscal cells at P2 displayed that the entire cell population was CD44+CD105+CD29+CD90+, suggesting that culturing meniscal cells results in selection of stem/progenitor cells (plastic adherence). Surface marker expression analysis showed differential expression patterns between markers depending on zone. Similar fraction of cells was detected to express both MSC markers CD90 and CD105 (7–10%) and similar fraction of cells expressed both MSC markers CD29 and CD44 (1–2%) in all three zones, indicating similar density of resident stem/progenitor cells in each zone. Importantly, WW showed significantly higher expression for all four MSC markers compared to the RR zone, indicating higher relative density of stem/progenitor resident cells in the WW zone.

Our results determine that CD31-expressing microvessels were present in all zones, including the WW zone, which was previously considered completely avascular. Additionally, stem/progenitor cells were shown to be present in all three zones of the menisci, including the WW zone, showcasing its regenerative potential.

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Introduction

Pre-clinical assessment of total knee replacements (TKR) can provide useful information about the constraint provided by an implant, and therefore help the surgeon decide the most appropriate configurations. For example, increasing the posterior tibial slope is believed to delay impingement in deep flexion and thus increase the maximal flexion angle of the knee, however it is unclear what effect this has on anterior-posterior (AP) constraint.

The current ASTM standard (F1223) for determining constraint gives little guidance on important factors such as medial- lateral (M:L) loading distribution, flexion angle or coupled secondary motions. Therefore, the aim of the study was to assess the sensitivity of the ASTM standard to these variations, and investigate how increasing the posterior tibial slope affects TKR constraint.