CARTILAGE

The objective of this pilot study was to determine time point(s) at which maximum concentration of fluticasone propionate (Cmax) occurs in synovial fluid and plasma in Beagle dog knees after intra-articular injection of EP-104IAR.

EP-104IAR is composed of fluticasone propionate drug crystals coated with heat-treated polyvinyl alcohol (PVA) to result in extended release properties. Thirty-two Beagle dogs had an injection of EP-104IAR into the knee joint at 2 different dose levels (0.6 mg and 12 mg). Outcome measures included plasma, synovial fluid, and articular cartilage fluticasone propionate concentrations as well as histological analysis of cartilage and synovium at a variety of time points up to 58 days postdosing.

Intra-articular administration of 0.6 and 12 mg EP-104IAR was well tolerated. Early minor abnormalities found on microscopy resolved by the end of the study. There were no quantifiable concentrations of fluticasone propionate in plasma of animals administered 0.6 mg at any of the sampling time points. Highest concentrations in plasma following 12 mg administration occurred 1 day postdose and declined with a half-life of approximately 45 days. Highest concentrations of fluticasone propionate in synovial fluid and cartilage generally occurred 5 days postdose in both dose groups and declined with a half-life of approximately 11 to 14 days.

EP-104IAR is capable of providing a safe and prolonged local exposure to a corticosteroid in the synovial joint while minimizing systemic exposure, with peak exposures occurring within a matter of days after dosing before declining in all tissues in a predictable manner.

Hyaline cartilage degenerative pathologies induce morphologic and biomechanical changes resulting in cartilage tissue damage. In pursuit of therapeutic options, electrical and mechanical stimulation have been proposed for improving tissue engineering approaches for cartilage repair. The purpose of this review was to highlight the effect of electrical stimulation and mechanical stimuli in chondrocyte behavior.

Different information sources and the MEDLINE database were systematically revised to summarize the different contributions for the past 40 years.

It has been shown that electric stimulation may increase cell proliferation and stimulate the synthesis of molecules associated with the extracellular matrix of the articular cartilage, such as collagen type II, aggrecan and glycosaminoglycans, while mechanical loads trigger anabolic and catabolic responses in chondrocytes.

The biophysical stimuli can increase cell proliferation and stimulate molecules associated with hyaline cartilage extracellular matrix maintenance.

The main goal of this study was to provide a proof-of-concept demonstrating that hyperosmolar K⁺ solutions can limit production of catabolic and inflammatory mediators in human osteoarthritic chondrocytes (OACs).

A 3-dimensional in vitro model with poly(ethylene glycol) diacrylate (PEGDA) hydrogels was used. Catabolic and pro-inflammatory protein production from encapsulated OACs was assessed following culture for 1 or 7 days in the presence or absence of 80 mM K⁺ gluconate, 80 mM sodium (Na⁺) gluconate, or 160 mM sucrose, each added to culture media (final osmolarity ~490 mOsm).

Relative to untreated controls, OACs treated with hyperosmolar (80 mM Na⁺ gluconate or 160 mM sucrose) solutions produced lower levels of catabolic and inflammatory mediators in a marker- and time-dependent manner (i.e., MMP-9 after 1 day; MCP-1 after 7 days (P ≤ 0.015)). In contrast, OAC treatment with 80 mM K⁺ gluconate reduced catabolic and inflammatory mediators to a greater extent (both the number of markers and degree of suppression) relative to untreated, Na⁺ gluconate, or sucrose controls (i.e., MMP-3, -9, -13, TIMP-1, MCP-1, and IL-8 after 1 day; MMP-1, -3, -9, -13, TIMP-1, MCP-1, and IL-8 after 7 days (P ≤ 0.029).

Hyperosmolar K⁺ solutions are capable of attenuating protein production of catabolic and inflammatory OA markers, providing the proof-of-concept needed for further development of a K⁺-based intra-articular injection for OA treatment. Moreover, K⁺ performed significantly better than Na⁺- or sucrose-based solutions, supporting the application of K⁺ toward improving irrigation solutions for joint surgery.

To identify the 50 most-cited articles in meniscal allograft transplantation (MAT) research and analyze their characteristics.

In September 2017, the Scopus database was queried to identify the 50 most-cited articles in MAT research. Variables analyzed include number of citations, publication year, journal, institution, country of origin, article type, study design, and level of evidence. Citation density was calculated for each article. The correlation between citation density and publication year and the correlation between level of evidence and number of citations, citation density, and publication year were computed.

The 50 most-cited articles were published in 12 journals between 1986 and 2011. The number of citations ranged from 59 to 290 (109.3 ± 48.6). Citation density ranged from 2.7 to 17.6 citations per year (7.0 ± 3.3). There was a positive correlation between citation density and publication year (r = +0.489, P < 0.001). Overall, 56% of the articles were clinical and 44% were basic science. Of the 28 clinical articles, 61% were level IV or V evidence. Level of evidence was not significantly correlated with number of citations (r = −0.059, P = 0.766), citation density (r = +0.030, P = 0.880), or publication year (r = −0.0009, P = 0.996).

This analysis provides the orthopedic community with a readily accessible list of the classic citations in MAT research and provides insight into the historical development of this procedure. Although there was a moderate positive correlation between citation density and publication year, articles with stronger levels of evidence were not more frequently cited despite the increasing trend toward evidence-based practice.

To analyze the topography of the opposite condyle to treat focal femoral condyle articular defects with an osteochondral allograft (OCA).

Three groups were created: Group 1, same condyle with same width; Group 2, opposite condyle with same width; Group 3, opposite condyle with different width. Computed tomography (CT) of 22 cadaveric femoral hemi-condyles was used to create 3-dimensional CT models that were exported into point-cloud models. Three zones of the donor condyle (anterior, middle, and posterior) were quantified. Four defect sizes were created (15, 18, 23, 25 mm) at the weight-bearing region. The defect was moved throughout each donor condyle zone and the least distance was calculated, defined as the shortest distance between the defect and the donor condyle.

The mean least distance increased with larger defect size in all groups, yet there was a less than 0.2 mm difference in the least distance among defect sizes. The 15, 18, and 23 mm defect models in Group 1 exhibited greater least distances at the anterior than middle and posterior zones. The 15 mm defect model exhibited greater least distance at the anterior zone than posterior zone in Group 3. However, there was a less than 0.05 mm difference in the mean least distance between zones. There was no significant difference in the least distance between groups.

OCAs from opposite condyles yield similar topographic matching to OCAs from the same condyles, suggesting that opposite condyles can be utilized. Clinical correlation and outcomes are necessary.

To characterize the graft survivorship and clinical outcomes of osteochondral allograft transplantation (OCA) of the knee in patients with an elevated body mass index (BMI).

Prospective data on 38 consecutive patients with a BMI ≥30 kg/m² treated with OCA from 2000 to 2015 were reviewed. Complications, reoperations, and patient responses to validated outcome measures were examined. Failures were defined by any removal/revision of the allograft or conversion to arthroplasty.

Thirty-one knees in 31 patients (mean age, 35.4 years [range, 17-61 years]; 87% male) met the inclusion criteria. Mean BMI was 32.9 kg/m² (range, 30-39 kg/m²). Mean chondral defect size was 6.4 cm² (range, 1.0-15.3 cm²). Prior to OCA, 23 patients (74%) had undergone previous surgery to the ipsilateral knee. Mean duration of follow-up was 4.1 years (range, 2-11 years). After OCA, 5 knees (13%) underwent conversion to unicompartmental (1) or total (4) knee arthroplasty. Two- and 5-year graft survivorship were 87% and 83%, respectively. At final follow-up, clinically significant improvements were noted in the pain (49.3-72.6) and physical functioning (52.9-81.3) subscales of the Short Form–36 (P ≤ 0.001), International Knee Documentation Committee subjective form (43.5-67.0; P = 0.002), Knee Outcome Survey–Activities of Daily Living (58.2-80.4; P = 0.002), and overall condition subscale of the Cincinnati Knee Rating System (4.7-6.9; P = 0.046).

OCA can be a successful midterm treatment option for focal cartilage defects of the knee in select patients with a BMI ≥30 kg/m².

To determine biomechanical effects of knee cartilage defect perimeter morphology based on cartilage strain and opposing subchondral bone contact.

Articular cartilage defects were created in 5 bovine femoral condyles: group 1, 45° inner bevel with 8-mm rim; group 2, vertical with 8-mm rim; and group 3, 45° outer bevel with 8-mm base. Samples were placed into a custom-machined micro–computed tomography tube and subjected to 800 N of axial loading. DICOM data were used to calculate cartilage thickness 4 and 6 mm from the center, distance between tibial cartilage surface and femoral subchondral bone, and contact width between tibial cartilage and subchondral bone. Strain 4 mm from the center and both absolute and change in distance (mm) to subchondral bone were compared between groups 1 and 2 using paired t tests. Strain at 6 mm and distance changed, loaded distance, and contact width (mm) were compared between groups using the Friedman test with post hoc analysis using Wilcoxon signed rank test.

No significant differences in rim strain were noted between groups 1 and 2 at 4 mm (P = 0.10) and between groups 1, 2, and 3 at 6 mm (P = 0.247) from the defect center. The loaded distance was significantly different between groups 1 and 3 (P = 0.013). No significant change in distance to the subchondral bone was found between groups (P = 0.156). The difference in subchondral bone contact area approached but did not reach significance (P = 0.074).

When debriding focal articular cartilage defects, establishment of an inner bevel decreases tissue deformation and contact with opposing subchondral bone.

Early detection of degenerative changes in the cartilage matrix composition is essential for evaluating early interventions that slow down osteoarthritis (OA) initiation. T1rho and T2 relaxation times were found to be effective for detecting early changes in proteoglycan and collagen content. To use these magnetic resonance imaging (MRI) methods, it is important to document the topographical variation in cartilage thickness, T1rho and T2 relaxation times in a healthy population. As OA is partially mechanically driven, the relation between these MRI-based parameters and localized mechanical loading during walking was investigated.

MR images were acquired in 14 healthy adults and cartilage thickness and T1rho and T2 relaxation times were determined. Experimental gait data was collected and processed using musculoskeletal modeling to identify weight-bearing zones and estimate the contact force impulse during gait. Variation of the cartilage properties (i.e., thickness, T1rho, and T2) over the femoral cartilage was analyzed and compared between the weight-bearing and non-weight-bearing zone of the medial and lateral condyle as well as the trochlea.

Medial condyle cartilage thickness was correlated to the contact force impulse (r = 0.78). Lower T1rho, indicating increased proteoglycan content, was found in the medial weight-bearing zone. T2 was higher in all weight-bearing zones compared with the non-weight-bearing zones, indicating lower relative collagen content.

The current results suggest that medial condyle cartilage is adapted as a long-term protective response to localized loading during a frequently performed task and that the weight-bearing zone of the medial condyle has superior weight bearing capacities compared with the non-weight-bearing zones.

Osteoarthritis (OA) literature makes minimal suggestion regarding age of disease onset or preventative strategies to reduce risk for onset in various populations. In 2005, the Centers for Disease Control and Prevention estimated that 33.6% of Americans 65+ years old were affected by OA; this cadaveric analysis suggests this is largely underestimated. The objective of this assessment is to identify at-risk populations for OA in the knee joint and make recommendations to prevent or delay disease onset.

Morphometric analyses of the articular cartilage of the tibial plateau were performed on cadaver specimens using Image Pro software on 3 age populations and surface area measurements for articular cartilage degradation were compared with donors’ reported ages, clinical histories, and occupations.

Data showed that by the seventh decade of life, when patients are in their 60s, articular cartilage degeneration on the tibial plateau had commenced in 100% of specimen. All “homemakers” displayed above-average medial tibial plateau degeneration (32.33% ± 24.85%) for their age group while simultaneously reporting pathologies in their clinical history that encourage a sedentary lifestyle.

This assessment identifies an occupational class with a propensity to develop disease and also identifies a more realistic time frame than previous advisory committees have produced regarding age of disease onset and initiation of preventative measures. It is recommended that strengthening of the hip abductors and the musculature supporting the knee commence early in adult life to avoid valgus collapse and shearing at the knee joint.

Assessing the therapeutic effects of a combination of intra-articular and intra-osseous infiltrations of platelet-rich plasma (PRP) to treat severe knee osteoarthritis (KOA) using intra-articular injections of PRP as the control group.

In this observational study, 60 patients suffering from severe KOA were treated with intra-articular infiltrations of PRP (IA group) or with a combination of intra-osseous and intra-articular infiltrations of PRP (IO group). Both groups were matched for sex, age, body mass index, and radiographic severity (III and IV degree according to Ahlbäck scale). Clinical outcome was evaluated at 2, 6, and 12 months, using the Knee injury and Osteoarthritis Outcome Score (KOOS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaires.

At 2, 6 and 12 months after treatment, IO group had a significant improvement in all KOOS and WOMAC subscales (P < 0.05). On the contrary, patients of the IA group did not improve in any of the scores. Sixteen out of 30 IO group patients showed minimal clinically important improvement (MCII) whereas 8 out of 30 IA group patients showed this response at 6 months (26.7%; 95% CI −0.4 to 49.9; P = 0.037). At 12 months, 14 patients of IO group and 5 patients of the IA group showed MCII (30%; 95% CI 4.3 to 51.9; P = 0.013). No differences between groups were observed at 2 months.

PRP intra-articular injections in severe KOA were not effective and did not provide any benefit. Combination of intra-articular and intra-osseous infiltrations of PRP was not clinically superior at 2 months, but it showed superior clinical outcomes at 6 and 12 months when compared with intra-articular injections of PRP.