Three‐dimensional imaging and analysis of human cartilage degeneration using Optical Coherence Tomography

Optical Coherence Tomography (OCT) is an evolving imaging technology allowing non‐destructive imaging of cartilage tissue at near‐histological resolution. This study investigated the diagnostic value of real time 3‐D OCT in comparison to conventional 2‐D OCT in the comprehensive grading of human cartilage degeneration. Fifty‐three human osteochondral samples were obtained from eight total knee arthroplasties. OCT imaging was performed by either obtaining a single two‐dimensional cross‐sectional image (2‐D OCT) or by collecting 100 consecutive parallel 2‐D OCT images to generate a volumetric data set of 8 × 8 mm (3‐D OCT). OCT images were assessed qualitatively according to a modified version of the DJD classification and quantitatively by algorithm‐based evaluation of surface irregularity, tissue homogeneity, and signal attenuation. Samples were graded according to the Outerbridge classification and statistically analyzed by one‐way ANOVA, Kruskal Wallis and Tukey's or Dunn's post‐hoc tests. Overall, the generation of 3‐D volumetric datasets and their multiple reconstructions such as rendering, surface topography, parametric, and cross‐sectional views proved to be of potential diagnostic value. With increasing distance to the mid‐sagittal plane and increasing degeneration, score deviations increased, too. In conclusion, 3‐D imaging of cartilage with image analysis algorithms adds considerable potential diagnostic value to conventional OCT diagnostics. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:651–659, 2015.     

Effect of highly purified capsaicin on articular cartilage and rotator cuff tendon healing: An in vivo rabbit study

Highly purified capsaicin has emerged as a promising injectable compound capable of providing sustained pain relief following a single localized treatment during orthopedic surgical procedures. To further assess its reliability for clinical use, the potential effect of highly purified capsaicin on articular cartilage metabolism as well as tendon structure and function warrants clarification. In the current study, rabbits received unilateral supraspinatus transection and repair with a single 1 ml injection of capsaicin (R + C), PEG‐only placebo (R + P), or saline (R + S) into the glenohumeral joint (GHJ). An additional group received 1 ml capsaicin onto an intact rotator cuff (I + C). At 18 weeks post‐op, cartilage proteoglycan (PG) synthesis and content as well as cell viability were similar (p > 0.05) across treatment groups. Biomechanical testing revealed no differences (p > 0.05) among tendon repair treatment groups. Similarly, histologic features of both cartilage and repaired tendons showed minimal differences across groups. Hence, in this rabbit model, a single injection of highly purified capsaicin into the GHJ does not induce a deleterious response with regard to cartilage matrix metabolism and cell viability, or rotator cuff healing. These data provide further evidence supporting the use of injectable, highly purified capsaicin as a safe alternative for management of postoperative pain following GHJ surgery. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1854–1860, 2015.     

Interspecies comparison of subchondral bone properties important for cartilage repair

Microfracture repair tissue in young adult humans and in rabbit trochlea is frequently of higher quality than in corresponding ovine or horse models or in the rabbit medial femoral condyle (MFC). This may be related to differences in subchondral properties since repair is initiated from the bone. We tested the hypothesis that subchondral bone from rabbit trochlea and the human MFC are structurally similar. Trochlea and MFC samples from rabbit, sheep, and horse were micro‐CT scanned and histoprocessed. Samples were also collected from normal and lesional areas of human MFC. The subchondral bone of the rabbit trochlea was the most similar to human MFC, where both had a relatively thin bone plate and a more porous and less dense character of subchondral bone. MFC from animals all displayed thicker bone plates, denser and less porous bone and thicker trabeculae, which may be more representative of older or osteoarthritic patients, while both sheep trochlear ridges and the horse lateral trochlea shared some structural features with human MFC. Since several cartilage repair procedures rely on subchondral bone for repair, subchondral properties should be accounted for when choosing animal models to study and test procedures that are intended for human cartilage repair. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:63–70, 2015.

     

High resolution T21 mapping in assessment of knee articular cartilage on 3T MRI

ObjectiveTo evaluate the spectrum of T21 values in healthy cartilage of young asymptomatic adults on high resolution 3T MRI.MethodsA total of 50 asymptomatic adult volunteers with age ranging from 18 to 35 years were enrolled for the study with the purpose of assessing T21 values in healthy cartilage without any degenerative changes. The articular cartilage was assessed on two sections, one each through the medial and lateral compartments. The cartilage was segmented into 8 regions through the tibio-femoral and patella-femoral joints. Further post processing was done using multiple ROI placement to delineate ROI areas for calculation of full thickness and zonal (superficial and deep) T21 values. Thus, a total of 1200 ROI areas (50 volunteers, 8 segments, and 3 areas for each segment) were assessed.ResultsThe results revealed a superior bulk T21 value of 29.2 ± 3.6 ms from the posterior medial femoral cartilage and 26.1 ± 3.1 ms from the patellar region. Intermediate values were obtained from posterior lateral femoral cartilage, central femoral cartilage, and trochlea. The tibial plateau cartilage had the lowest values – 19.6 ± 2.6 ms for the medial tibial plateau and 20.6 ± 2.8 ms for lateral tibial plateau. The study demonstrated substantial regional physiological variation existing in the T21 values across various regions of the knee joint, which could be attributed to varying amounts of shearing forces across the joint. No significant differences were noted in bulk T21 values between the two genders, with only the trochlear segment revealing significantly increased values in males (p = 0.007). All the cartilage segments revealed significantly increased T21 values in the superficial zone as compared to the deep zone.ConclusionThere is a significant regional difference in the bulk T21 values of articular cartilage in a normal physiological state across various joint segments. A zonal gradient with increasing values from the deep to the superficial zone also exists. These findings can prove invaluable in assessing changes in T21 values occurring in diseased/degenerative cartilage.     

Biocompatible implant mimicking cartilage: A new horizon for reconstructive facial field

Cartilage is avascular with limited to no regenerative capacity, so its loss could be a challenge for reconstructive surgery. Current treatment options for damaged cartilage are also limited. In this aspect there is a tremendous need to develop an ideal cartilage-mimicking biomaterial that could repair maxillofacial defects. Considering this fact in this study we have prepared twelve silicone-based materials (using Silicone 40, 60, and 80) reinforced with hydroxyapatite, tri-calcium phosphate, and titanium dioxide which itself has proven their efficacy in several studies and able to complement the shortcomings of using silicones. Among the mechanical properties (Young’s modulus, tensile strength, percent elongation, and hardness), hardness of Silicone-40 showed similarities with goat ear (P > .05). Silicone peaks have been detected in FTIR. Both AFM morphology and SEM images of the samples confirmed more roughed surfaces. All the materials were nonhemolytic in hemocompatibility tests, but among the twelve materials S2, S3, S5, and S6 showed the least hemolysis. For all tested bacterial strains, adherence was lower on each material than that grown on the plain industrial silicone material which was used as a positive control. S2, S3, S5, and S6 samples were selected as the best based on mechanical characterizations, surface characterizations, in vitro hemocompatibility tests and bacterial adherence activity. So, outcomes of this present study would be promising when developing ideal cartilage-mimicking biocomposites and their emerging applications to treat maxillofacial defects due to cartilage damage.     

Initiating factors for the onset of OA: A systematic review of animal bone and cartilage pathology in OA

There is controversy over whether bone or cartilage is primarily involved in osteoarthritis (OA) pathogenesis; this is important for targeting early interventions. We explored evidence from animal models of knee OA by preforming a systematic review of PubMed, Scopus, and Web of Science for original articles reporting subchondral bone and cartilage pathology in animal models with epiphyseal closure. Extracted data included: method of induction; animal model; cartilage and bone assessment and method; meniscal assessment; skeletal maturity; controls; and time points assessed. Quality scoring was performed. The best evidence was synthesized from high-quality skeletally mature models, without direct trauma to tissues of interest and with multiple time points. Altogether, 2849 abstracts were reviewed. Forty-seven papers were included reporting eight different methods of inducing OA, six different species, six different methods of assessing cartilage, five different bone structural parameters, and four assessed meniscus as a potential initiator. Overall, the simultaneous onset of OA in cartilage and bone was reported in 82% of datasets, 16% reported bone onset, and 2% reported cartilage onset. No dataset containing meniscal data reported meniscal onset. However, using the best evidence synthesis (n = 8), five reported simultaneous onset when OA was induced, while three reported bone onset when OA occurred spontaneously; none reported cartilage onset. In summary, there is a paucity of well-designed studies in this area which makes the conclusions drawn conjectures rather than proven certainties. However, within the limitation of data quality, this review suggests that in animal models, the structural onset of knee OA occurs either in bone prior to cartilage pathology or simultaneously.     

Dual contrast in computed tomography allows earlier characterization of articular cartilage over single contrast

Cationic computed tomography contrast agents are more sensitive for detecting cartilage degeneration than anionic or non-ionic agents. However, osteoarthritis-related loss of proteoglycans and increase in water content contrarily affect the diffusion of cationic contrast agents, limiting their sensitivity. The quantitative dual-energy computed tomography technique allows the simultaneous determination of the partitions of iodine-based cationic (CA4+) and gadolinium-based non-ionic (gadoteridol) agents in cartilage at diffusion equilibrium. Normalizing the cationic agent partition at diffusion equilibrium with that of the non-ionic agent improves diagnostic sensitivity. We hypothesize that this sensitivity improvement is also prominent during early diffusion time points and that the technique is applicable during contrast agent diffusion. To investigate the validity of this hypothesis, osteochondral plugs (d = 8 mm, N = 33), extracted from human cadaver (n = 4) knee joints, were immersed in a contrast agent bath (a mixture of CA4+ and gadoteridol) and imaged using the technique at multiple time points until diffusion equilibrium. Biomechanical testing and histological analysis were conducted for reference. Quantitative dual-energy computed tomography technique enabled earlier determination of cartilage proteoglycan content over single contrast. The correlation coefficient between human articular cartilage proteoglycan content and CA4+ partition increased with the contrast agent diffusion time. Gadoteridol normalized CA4+ partition correlated significantly (P < .05) with Mankin score at all time points and with proteoglycan content after 4 hours. The technique is applicable during diffusion, and normalization with gadoteridol partition improves the sensitivity of the CA4+ contrast agent.     

Combined Injury to the ACL and Lateral Meniscus Alters the Geometry of Articular Cartilage and Meniscus Soon After Initial Trauma

Combined injury to the anterior cruciate ligament (ACL) and meniscus is associated with earlier onset and increased rates of post-traumatic osteoarthritis compared with isolated ACL injury. However, little is known about the initial changes in joint structure associated with these different types of trauma. We hypothesized that trauma to the ACL and lateral meniscus has an immediate effect on morphometry of the articular cartilage and meniscus about the entire tibial plateau that is more pronounced than an ACL tear without meniscus injury. Subjects underwent magnetic resonance imaging scanning soon after injury and prior to surgery. Those that suffered injury to the ACL and lateral meniscus underwent changes in the lateral compartment (increases in the posterior–inferior directed slopes of the articular cartilage surface, and the wedge angle of the posterior horn of the meniscus) and medial compartment (the cartilage-to-bone height decreased in the region located under the posterior horn of the meniscus, and the thickness of cartilage increased and decreased in the mid and posterior regions of the plateau, respectively). Subjects that suffered an isolated ACL tear did not undergo the same magnitude of change to these articular structures. A majority of the changes in morphometry occurred in the lateral compartment of the knee; however, change in the medial compartment of the knee with a normal appearing meniscus also occurred. Statement of clinical significance: Knee injuries that involve combined trauma to the ACL and meniscus directly affect both compartments of the knee, even if the meniscus and articular cartilage appears normal upon arthroscopic examination. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:759-767, 2020     

Exploring Penicillin G as an Intrawound Antibiotic Powder for Prevention of Postoperative Shoulder Infections: Does It Exhibit In Vitro Chondrotoxicity?

Cutibacterium acnes (C. acnes) is a significant insidious pathogen for postoperative infections in shoulder surgery. Studies have demonstrated that certain topical antibiotic powders used have the potential for chondrotoxicity. Benzylpenicillin, commonly referred to as Penicillin G (Pen G) has the lowest minimum inhibitory concentration (MIC) for C. acnes. There is no research regarding the topical application of Pen G during shoulder surgery, nor has its chondrocyte toxicity been previously investigated. This study sought to characterize the in vitro chondrocyte toxicity of Pen G. Culture-derived bovine chondrocytes were exposed to serial Pen G concentrations and compared with a positive and negative control. A negative control of growth medium and positive control of 1% Triton solution. The chondrocyte viability was assessed via spectrophotometer absorbance. The treatment groups were analyzed using one-way repeated measures analysis of variance and Pearson's correlation analysis. The chondrocyte viability was significantly higher for all Pen G concentrations as compared with the positive control (p < 0.001). All concentrations of Pen G exhibited continued chondrocyte metabolic activity over time. Analysis of variance, independent of time, demonstrated no significant decrease in chondrocyte viability for Pen G concentrations ≤6.25 mg/ml, as compared with the negative control (p > 0.05). Pen G demonstrated a significant negative correlation with its concentration and absorbance (r = 0.371, p < 0.001), however, concentrations ≤6.25 mg/ml did not demonstrate a significant decrease in chondrocyte viability (p = 0.063). Pen G in concentrations appropriate for C. acnes is not significantly chondrotoxic and may be safe for intrawound application. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:726-730, 2020