Structural clues to articular calcified cartilage function: A descriptive review of this crucial interface tissue.

Articular calcified cartilage (ACC) has been dismissed, by some, as a remnant of endochondral ossification without functional relevance to joint articulation or weight-bearing. Recent research indicates that morphologic and metabolic ACC features may be important, reflecting knee joint osteoarthritis (OA) predisposition. ACC is less investigated than neighbouring joint tissues, with its component chondrocytes and mineralised matrix often being either ignored or integrated into analyses of hyaline articular cartilage and subchondral bone tissue respectively. Anatomical variation in ACC is recognised between species, individuals and age groups, but the selective pressures underlying this variation are unknown. Consequently, optimal ACC biomechanical features are also unknown as are any potential locomotory roles. This review collates descriptions of ACC anatomy and biology in health and disease, with a view to revealing its structure/function relationship and highlighting potential future research avenues. Mouse models of healthy and OA joint ageing have shown disparities in ACC load-induced deformations at the knee joint. This raises the hypothesis that ACC response to locomotor forces over time may influence, or even underlie, the bony and hyaline cartilage symptoms characteristic of OA. To effectively investigate the ACC, greater resolution of joint imaging and merging of hierarchical scale data will be required. An appreciation of OA as a 'whole joint disease' is expanding, as is the possibility that the ACC may be a key player in healthy ageing and in the transition to OA joint pathology.

Criterion validity of ultrasound in the identification of calcium pyrophosphate crystal deposits at the knee: an OMERACT ultrasound study.

OBJECTIVE: To evaluate the discriminatory ability of ultrasound in calcium pyrophosphate deposition disease (CPPD), using microscopic analysis of menisci and knee hyaline cartilage (HC) as reference standard. METHODS: Consecutive patients scheduled for knee replacement surgery, due to osteoarthritis (OA), were enrolled. Each patient underwent ultrasound examination of the menisci and HC of the knee, scoring each site for presence/absence of CPPD. Ultrasound signs of inflammation (effusion, synovial proliferation and power Doppler) were assessed semiquantitatively (0-3). The menisci and condyles, retrieved during surgery, were examined microscopically by optical light microscopy and by compensated polarised microscopy. CPPs were scored as present/absent in six different samples from the surface and from the internal part of menisci and cartilage. Ultrasound and microscopic analysis were performed by different operators, blinded to each other's findings. RESULTS: 11 researchers from seven countries participated in the study. Of 101 enrolled patients, 68 were included in the analysis. In 38 patients, the surgical specimens were insufficient. The overall diagnostic accuracy of ultrasound for CPPD was of 75%-sensitivity of 91% (range 71%-87% in single sites) and specificity of 59% (range 68%-92%). The best sensitivity and specificity were obtained by assessing in combination by ultrasound the medial meniscus and the medial condyle HC (88% and 76%, respectively). No differences were found between patients with and without CPPD regarding ultrasound signs of inflammation. CONCLUSION: Ultrasound demonstrated to be an accurate tool for discriminating CPPD. No differences were found between patents with OA alone and CPPD plus OA regarding inflammation.

Damage to the human lumbar cartilage endplate and its clinical implications.

The cartilaginous endplate (CEP) is a thin layer of hyaline cartilage, and plays an important role in the diffusion of nutrients into the intervertebral discs. Its damage may seriously affect the disc degeneration, and result in low back pain (LBP). However, the structural features of damaged CEPs have not been well characterized, and this hinders our understanding of the etiology of disc degeneration and pain. To present the structural features of micro-damaged CEPs in patients with disc degeneration and LBP that might even be regarded as an initial factor for disc degeneration, we performed a histological study of micro-damaged CEPs harvested from human lumbar intervertebral discs and analyzed its clinical implications. Human lumbar CEPs were excised from 35 patients (mean age 60.91 years) who had disc degeneration and LBP. Control tissue was obtained from 15 patients (mean age 54.67 years) with lumbar vertebral burst fractures. LBP and disability were assessed clinically, and all patients underwent anterior vertebral body fusion surgery. CEPs together with some adjacent nucleus pulposus (NP) were sectioned at 4 µm, and stained using H&E, Safranin O/Fast Green, and Alcian Blue. Immunostaining and PCR were used to identify various markers of degeneration, innervation, and inflammation. Histology demonstrated physical micro-damage in 14/35 CEPs from the disc degeneration group. Six major types of damage could be distinguished: fissure, traumatic nodes, vascular mimicry, incorporation of NP tissue within the CEP, incorporation of bone within the CEP, and incorporation of NP and bone within the CEP. Pain and disability scores (ODI: p = 0.0190; JOA: p = 0.0205; JOABPEQ: p = 0.0034) were significantly higher in those with micro-damaged CEPs (N = 14) than in those with non-damaged CEPs (N = 21). CEP damage was significantly associated with elevated MMP3 (p = 0.043), MMP13 (p = 0.0191), ADAMTS5 (p = 0.0253), TNF-α (p = 0.0011), and Substance P (p = 0.0028), and with reduced Sox9 (p = 0.0212), aggrecan (p = 0.0127), and type II collagen (p = 0.0139). In conclusion, we presented a new classification of human lumbar micro-damaged CEPs. Furthermore, we verify disc degeneration, innervation, and discogenic pain in micro-damaged CEPs.

NKX3.1 a useful marker for mesenchymal chondrosarcoma: An immunohistochemical study.

INTRODUCTION: Mesenchymal chondrosarcoma is a rare subtype of chondrosarcoma. The tumor has a characteristic bimorphic pattern with areas of poorly differentiated small round cell component and interspersed islands of well differentiated hyaline cartilage. Histological diagnosis of mesenchymal chondrosarcoma is very challenging especially in small biopsies when tumor presents with little cartilaginous component. In such cases, it is very difficult to distinguish mesenchymal chondrosarcoma from other round blue cell tumors like Ewing's sarcoma, rhabdomyosarcoma, small cell osteosarcoma and desmoplastic round blue cell tumor. Immunohistochemically, mesenchymal chondrosarcoma stains positive for NKX2.2, CD99, S100 and SOX9. This immunoprofile is non-specific and overlaps with other round blue cell tumors. Till recently, there was no reliable immunohistochemical marker to differentiate mesenchymal chondrosarcoma from other round blue cell tumors. NKX3.1, though widely used as a diagnostic biomarker for prostatic adenocarcinoma, has been recently proposed by Yoshida et al. (2020) as a unique marker of mesenchymal chondrosarcoma and EWSR1-NFATC2 sarcoma. OBJECTIVE: The aim of our study was to further explore utility of NKX3.1 as a diagnostic marker of mesenchymal chondrosarcoma. MATERIAL & METHODS: We applied NKX3.1 immunohistochemistry to 21 cases of mesenchymal chondrosarcoma and 32 cases of other round blue cell tumors. RESULTS: 14 out of 21 cases (66.7%) of mesenchymal chondrosarcoma stained positive for NKX3.1 with nuclear expression in small round component. Cartilaginous component was predominantly negative. All other round blue cell tumors showed negative results. CONCLUSION: Based on our study results we suggest that NKX3.1 is a useful immunohistochemical marker in differentiating mesenchymal chondrosarcoma from its histological mimics.

Implantation of Various Cell-Free Matrixes Does Not Contribute to the Restoration of Hyaline Cartilage within Full-Thickness Focal Defects.

Articular cartilage is a highly organized tissue that has a limited ability to heal. Tissue engineering is actively exploited for joint tissue reconstruction in numerous cases of articular cartilage degeneration associated with trauma, arthrosis, rheumatoid arthritis, and osteoarthritis. However, the optimal scaffolds for cartilage repair are not yet identified. Here we have directly compared five various scaffolds, namely collagen-I membrane, collagen-II membrane, decellularized cartilage, a cellulose-based implant, and commercially available Chondro-Gide® (Geistlich Pharma AG, Wolhusen, Switzerland) collagen membrane. The scaffolds were implanted in osteochondral full-thickness defects, formed on adult Wistar rats using a hand-held cutter with a diameter of 2.0 mm and a depth of up to the subchondral bone. The congruence of the articular surface was almost fully restored by decellularized cartilage and collagen type II-based scaffold. The most vivid restoration was observed 4 months after the implantation. The formation of hyaline cartilage was not detected in any of the groups. Despite cellular infiltration into scaffolds being observed in each group except cellulose, neither chondrocytes nor chondro-progenitors were detected. We concluded that for restoration of hyaline cartilage, scaffolds have to be combined either with cellular therapy or morphogens promoting chondrogenic differentiation.

Main and Minor Types of Collagens in the Articular Cartilage: The Role of Collagens in Repair Tissue Evaluation in Chondral Defects.

Several collagen subtypes have been identified in hyaline articular cartilage. The main and most abundant collagens are type II, IX and XI collagens. The minor and less abundant collagens are type III, IV, V, VI, X, XII, XIV, XVI, XXII, and XXVII collagens. All these collagens have been found to play a key role in healthy cartilage, regardless of whether they are more or less abundant. Additionally, an exhaustive evaluation of collagen fibrils in a repaired cartilage tissue after a chondral lesion is necessary to determine the quality of the repaired tissue and even whether or not this repaired tissue is considered hyaline cartilage. Therefore, this review aims to describe in depth all the collagen types found in the normal articular cartilage structure, and based on this, establish the parameters that allow one to consider a repaired cartilage tissue as a hyaline cartilage.

Role of Scaffolds, Subchondral, Intra-Articular Injections of Fresh Autologous Bone Marrow Concentrate Regenerative Cells in Treating Human Knee Cartilage Lesions: Different Approaches and Different Results.

The value of bone marrow aspirate concentrates for treatment of human knee cartilage lesions is unclear. Most of the studies were performed with intra-articular injections. However, subchondral bone plays an important role in the progression of osteoarthritis. We investigated by a literature review whether joint, subchondral bone, or/and scaffolds implantation of fresh autologous bone marrow aspirate concentrated (BMAC) containing mesenchymal stem cells (MSCs) would improve osteoarthritis (OA). There is in vivo evidence that suggests that all these different approaches (intra-articular injections, subchondral implantation, scaffolds loaded with BMAC) can improve the patient. This review analyzes the evidence for each different approach to treat OA. We found that the use of intra-articular injections resulted in a significant relief of pain symptoms in the short term and was maintained in 12 months. However, the clinical trials indicate that the application of autologous bone marrow concentrates in combination with scaffolds or in injection in the subchondral bone was superior to intra-articular injection for long-term results. The tendency of MSCs to differentiate into fibrocartilage affecting the outcome was a common issue faced by all the studies when biopsies were performed, except for scaffolds implantation in which some hyaline cartilage was found. The review suggests also that both implantation of subchondral BMAC and scaffolds loaded with BMAC could reduce the need for further surgery.

Cartilage calcification is associated with histological degeneration of the knee joint: a highly prevalent, age-independent systemic process.

OBJECTIVES: To investigate if cartilage calcification (CC) is a systemic process, the purpose of this study was to determine the prevalence and the amount of meniscal/hyaline CC of the knee joint in the general population by high-resolution imaging (DCR) and to evaluate the association between CC with cartilage degeneration and age. METHODS: Cross-sectional DCR-study of 180 knee joints of 90 donors (42 female/48 male, mean age 62.3y). Histological hyaline (OARSI) and meniscal (Krenn) cartilage degeneration was determined of all knees. RESULTS: CC was observed in 100% of the donors (bilaterally in 98%), hyaline cartilage calcification (HCC) in 92% and meniscal calcification (MC) in 100%. CC was detected in more than three out of six distinct cartilage areas in 84.4% of all knees. The mean amount of CC correlated between both sides of donors, the different analyzed areas of the knee joint and between the various types of cartilage structures. There was more calcification in meniscal than in hyaline cartilage (factor 5.3) and in the medial than the lateral compartment (factor 1.2). HCC/MC were already detectable with only mild cartilage lesions and the amount correlated with histological cartilage degeneration, but not with age. CONCLUSIONS: The present study provides evidence that meniscal and hyaline CC occurs in a pattern that is compatible with CC being a systemically driven process and that meniscal fibrocartilage is more prone to calcification than hyaline cartilage. Furthermore, the age-independent association between the amount of CC and the grade of degeneration in both hyaline and meniscal cartilage, suggests that CC is an obligatory early event in initiating cartilage degeneration.

The human arthritic hip joint is a source of mesenchymal stromal cells (MSCs) with extensive multipotent differentiation potential.

BACKGROUND: While multiple in vitro studies examined mesenchymal stromal cells (MSCs) derived from bone marrow or hyaline cartilage, there is little to no data about the presence of MSCs in the joint capsule or the ligamentum capitis femoris (LCF) of the hip joint. Therefore, this in vitro study examined the presence and differentiation potential of MSCs isolated from the bone marrow, arthritic hyaline cartilage, the LCF and full-thickness samples of the anterior joint capsule of the hip joint. METHODS: MSCs were isolated and multiplied in adherent monolayer cell cultures. Osteogenesis and adipogenesis were induced in monolayer cell cultures for 21 days using a differentiation medium containing specific growth factors, while chondrogenesis in the presence of TGF-ß1 was performed using pellet-culture for 27 days. Control cultures were maintained for comparison over the same duration of time. The differentiation process was analyzed using histological and immunohistochemical stainings as well as semiquantitative RT-PCR for measuring the mean expression levels of tissue-specific genes. RESULTS: This in vitro research showed that the isolated cells from all four donor tissues grew plastic-adherent and showed similar adipogenic and osteogenic differentiation capacity as proven by the histological detection of lipid droplets or deposits of extracellular calcium and collagen type I. After 27 days of chondrogenesis proteoglycans accumulated in the differentiated MSC-pellets from all donor tissues. Immunohistochemical staining revealed vast amounts of collagen type II in all differentiated MSC-pellets, except for those from the LCF. Interestingly, all differentiated MSCs still showed a clear increase in mean expression of adipogenic, osteogenic and chondrogenic marker genes. In addition, the examination of an exemplary selected donor sample revealed that cells from all four donor tissues were clearly positive for the surface markers CD44, CD73, CD90 and CD105 by flow cytometric analysis. CONCLUSIONS: This study proved the presence of MSC-like cells in all four examined donor tissues of the hip joint. No significant differences were observed during osteogenic or adipogenic differentiation depending on the source of MSCs used. Further research is necessary to fully determine the tripotent differentiation potential of cells isolated from the LCF and capsule tissue of the hip joint.

The Presence of Pericholedochal Hyaline Cartilage in Biliary Atresia: A Report and A Review.

Background: The presence of cartilage in extra hepatic biliary tree is an unusual finding. An isolated presence of the cartilage is possibly heterotopic or occurs as a metaplastic response to the inflammatory insult.Material and methods: We had examined the liver biopsy and the resected specimen of a biliary atresia (BA) after Kasai procedure.Results: There was hyaline cartilage around the common hepatic and common bile duct in a 3-months-old male infant with distal obstructive cholangiopathy on liver biopsy and had positive serum IgM for cytomegalovirus (CMV). Similar findings could not be documented in the pericholedochal tissue of any of the 25 other pediatric cases operated for BA or choledochal cyst and three neonatal autopsies performed for liver-related deaths.Conclusion: Peri-bile duct cartilage is a unique finding and could represent an unusual form of heterotopia or connective tissue metaplasia.

Commercial Products for Osteochondral Tissue Repair and Regeneration.

The osteochondral tissue represents a complex structure composed of four interconnected structures, namely hyaline cartilage, a thin layer of calcified cartilage, subchondral bone, and cancellous bone. Due to the several difficulties associated with its repair and regeneration, researchers have developed several studies aiming to restore the native tissue, some of which had led to tissue-engineered commercial products. In this sense, this chapter discusses the good manufacturing practices, regulatory medical conditions and challenges on clinical translations that should be fulfilled regarding the safety and efficacy of the new commercialized products. Furthermore, we review the current osteochondral products that are currently being marketed and applied in the clinical setting, emphasizing the advantages and difficulties of each one.

Arthroscopic Cartilage Lesion Preparation in the Human Cadaveric Knee Using a Curette Technique Demonstrates Clinically Relevant Histologic Variation.

PURPOSE: To examine the quality of arthroscopic cartilage debridement using a curette technique by comparing regional and morphologic variations within cartilage lesions prepared in human cadaveric knee specimens for the purpose of cartilage repair procedures. A secondary aim was to compare the histologic properties of cartilage lesions prepared by surgeons of varying experience. METHODS: Standardized cartilage lesions (8 mm × 15 mm), located to the medial/lateral condyle and medial/lateral trochlea were created within 12 human cadaver knees by 40 orthopaedic surgeons. Participants were instructed to create full-thickness cartilage defects within the marked area, shouldered by uninjured vertical walls of cartilage, and to remove the calcified cartilage layer, without violating the subchondral plate. Histologic specimens were prepared to examine the verticality of surrounding cartilage walls at the front and rear aspects of the lesions, and to characterize the properties of the surrounding cartilage, the cartilage wall profile, the debrided lesion depth, bone sinusoid access, and the bone surface profile. Comparative analysis of cartilage wall verticality measured as deviation from perpendicular was performed, and Spearman's rank correlation analysis was used to examine associations between debrided wall verticality and surgeon experience. RESULTS: Mean cartilage wall verticality relative to the base of the lesion was superior at the rear aspect of the lesion compared to the front aspect (12.9° vs 29.2°, P < .001). Variability was identified in the morphology of the surrounding cartilage (P < .001), cartilage wall profile (P = .016), debrided lesion depth (P = .028), bone surface profile (P = .040), and bone sinusoid access (P = .009), with sinusoid access identified in 42% of cases. There was no significant association of cartilage lesion wall verticality and surgeon years in practice (rs = 0.161, P = .065) or arthroscopic caseload (rs = -0.071, P = .419). CONCLUSIONS: Arthroscopic cartilage lesion preparation using standard curette technique in a human cadaveric knee model results in inferior perpendicularity of the surrounding cartilage walls at the front aspect of the defect, compared to the rear aspect. This technique has shown significant variability in the depth of debridement, with debridement depths identified as either too superficial or too deep to the calcified cartilage layer in more than 60% of cases in this study. Surgeon experience does not appear to impact the morphologic properties of cartilage lesions prepared arthroscopically using ring curettes. CLINICAL RELEVANCE: To optimize restoration of hyaline-like cartilage tissue, careful attention to prepared cartilage lesion morphology is advised when arthroscopically performing cartilage repair, given the tendency for standard curette technique to create inferior verticality of cartilage walls at the front of the lesion, and the variable depth of debridement achieved.

Chondrosarcoma: A Rare Misfortune in Aging Human Cartilage? The Role of Stem and Progenitor Cells in Proliferation, Malignant Degeneration and Therapeutic Resistance.

Unlike other malignant bone tumors including osteosarcomas and Ewing sarcomas with a peak incidence in adolescents and young adults, conventional and dedifferentiated chondrosarcomas mainly affect people in the 4th to 7th decade of life. To date, the cell type of chondrosarcoma origin is not clearly defined. However, it seems that mesenchymal stem and progenitor cells (MSPC) in the bone marrow facing a pro-proliferative as well as predominantly chondrogenic differentiation milieu, as is implicated in early stage osteoarthritis (OA) at that age, are the source of chondrosarcoma genesis. But how can MSPC become malignant? Indeed, only one person in 1,000,000 will develop a chondrosarcoma, whereas the incidence of OA is a thousandfold higher. This means a rare coincidence of factors allowing escape from senescence and apoptosis together with induction of angiogenesis and migration is needed to generate a chondrosarcoma. At early stages, chondrosarcomas are still assumed to be an intermediate type of tumor which rarely metastasizes. Unfortunately, advanced stages show a pronounced resistance both against chemo- and radiation-therapy and frequently metastasize. In this review, we elucidate signaling pathways involved in the genesis and therapeutic resistance of chondrosarcomas with a focus on MSPC compared to signaling in articular cartilage (AC).

[Current Options and Importance of Imaging of the Hyaline Articular Cartilage of the Knee Prior to the Surgery - a Different Perspective of an Orthopaedic Surgeon and a Radiologist]. / Soucasné moznosti a význam zobrazování hyalinní chrupavky kolenního kloubu pred operacním zákrokem ­ rozdílný pohled ortopeda a radiologa.

The authors present an overview of the commonly used techniques and new trends of the cartilage imaging, especially postoperatively, and also discuss the potential of MRI imaging of the cartilage from the perspective of an experienced orthopaedic surgeon. In conclusion, the authors propose possible explanations for the potential discrepancies between the MRI and the arthroscopic findings. Hyaline cartilage damage and subsequent reparation of this tissue is one of the topical issues of orthopaedics and traumatology. Due to the expanding possibilities of treatment of this tissue and a relatively good effect of the surgery, the number of patients indicated for magnetic resonance imaging prior to the surgery has been on an increase. To make a decision concerning the subsequent type of treatment, it is necessary to get an idea of the cartilage cover condition, articular surfaces and also of the associated pathologies. The degree of cartilage damage can be assessed by arthroscopy or magnetic resonance imaging, which provides also the possibility of the subchondral lesion detection. Thanks to the noninvasive nature of the MRI examination, it has become the most important method in full imaging of the articular cartilage. The MRI of the cartilage has many options and at present the evaluation of the hyaline cartilage should be an integral part of each MRI examination of joints. For a more accurate assessment of the cartilage there are several advanced techniques available that can be used not only for preoperative diagnostics, but also for monitoring after the surgery. Key words: hyaline cartilage, magnetic resonance, arthroscopy.

Large enchondroma of the thoracic spine: a rare case report and review of the literature.

BACKGROUND: Enchondroma, a subtype of chondroma, originates from the medullary cavity of the bone and produces an expansile growth pattern. Enchondroma located in the spine is rare and a few cases of large thoracic enchondroma have been reported. The authors document a rare case of large enchondroma in the thoracic spine of a 49-year-old woman, and discuss its clinical, radiological and histopathological characteristics. CASE PRESENTATION: The patient presented with rapidly progressive and severe pain on her upper back. Magnetic resonance imaging revealed an expansile lesion at the posterior elements of T3 that was hypointense on T1-weighted images and mixed iso- to hyperintense on T2-weighted images. Administration of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) resulted in heterogeneous enhancement. During surgery, a large tumor of 4.2cm × 4.7cm × 2.1cm was resected along with the lamina and spinous process. Histological examination revealed that the tumor consisted of mature hyaline cartilage with typical chondrocytes, indicating that it was an enchondroma. CONCLUSIONS: Despite its benign-growing nature, enchondroma should be examined closely for signs of enchondromatosis and enchondrosarcoma. Complete surgical resection is the treatment of choice for immediate relief of symptoms and avoidance of recurrence.

Comparative efficacy of cartilage repair procedures in the knee: a network meta-analysis.

PURPOSE: While numerous randomized controlled trials have compared surgical treatments for cartilage defects of the knee, the comparative efficacy of these treatments is still poorly understood. The goal of this network meta-analysis was to synthesize these randomized data into a comprehensive model allowing pairwise comparisons of all treatment options and treatment rankings based on multiple measures of efficacy. We hypothesized that advanced chondral procedures would have improved outcomes when compared to microfracture. METHODS: The MEDLINE, COCHRANE and EMBASE databases were searched systematically up to January 2015. The primary outcome was re-operation measured at 2, 5 and 10 years. Secondary outcomes included Tegner and Lysholm scores, the presence of hyaline cartilage on post-operative biopsy and graft hypertrophy. A random-effects network meta-analysis was performed, and the results are presented as odds ratios and mean differences with 95 % CIs. We ranked the comparative effects of all treatments with surface under the cumulative ranking probabilities. RESULTS: Nineteen RCT from 15 separate cohorts including 855 patients were eligible for inclusion. No differences were seen in re-operation rates at 2 years. At 5 years osteochondral autografts (OC Auto) had a lower re-operation rate than microfracture (OR 0.03, 95 % CI 0.00-0.49), and at 10 years OC Auto had a lower re-operation rate than microfracture (OR 0.34, 95 % CI 0.12-0.92), but a higher re-operation rate than second-generation ACI (OR 5.81, 95 % CI 2.33-14.47). No significant differences in Tegner or Lysholm scores were seen at 2 years. Functional outcome data at 5 and 10 years were not available. Hyaline repair tissue was more common with OC Auto (OR 16.13, 95 % CI 2.80-92.91) and 2nd generation ACI (OR 7.69, 95 % CI 1.17-50) than microfracture, though the clinical significance of this is unknown. Second-generation ACI (OR 0.12, 95 % CI 0.02-0.59) and MACI (OR 0.13, 95 % CI 0.03-0.59) had significantly lower rates of graft hypertrophy than first-generation ACI. Second-generation ACI, OC Auto and MACI were the highest ranked treatments (in order) when all outcome measures were included. CONCLUSIONS: Microfracture and advanced cartilage repair techniques have similar re-operation rates and functional outcomes at 2 years. However, advanced repair techniques provide higher-quality repair tissue and might afford lower re-operation rates at 5 and 10 years. LEVEL OF EVIDENCE: Meta-analysis studies, Level I.

Using synchrotron X-ray phase-contrast micro-computed tomography to study tissue damage by laser irradiation.

BACKGROUND AND OBJECTIVE: The aim of this study was to determine if X-ray micro-computed tomography could be used to locate and characterize tissue damage caused by laser irradiation and to describe its advantages over classical histology for this application. STUDY DESIGN/MATERIALS AND METHODS: A surgical CO2 laser, operated in single pulse mode (100 milliseconds) at different power settings, was used to ablate different types of cadaveric animal tissues. Tissue samples were then harvested and imaged with synchrotron X-ray phase-contrast and micro-computed tomography to generate stacks of virtual sections of the tissues. Subsequently, Fiji (ImageJ) software was used to locate tissue damage, then to quantify volumes of laser ablation cones and thermal coagulation damage from 3D renderings of tissue image stacks. Visual comparisons of tissue structures in X-ray images with those visible by classic light microscopy histology were made. RESULTS: We demonstrated that micro-computed tomography could be used to rapidly identify areas of surgical laser ablation, vacuolization, carbonization, and thermally coagulated tissue. Quantification and comparison of the ablation crater, which represents the volume of ablated tissue, and the thermal coagulation zone volumes were performed faster than we could by classical histology. We demonstrated that these procedures can be performed on fresh hydrated and non-sectioned plastic embedded tissue. CONCLUSION: We demonstrated that the application of non-destructive micro-computed tomography to the visualization and analysis of laser induced tissue damage without tissue sectioning is possible. This will improve evaluation of new surgical lasers and their corresponding effect on tissues. Lasers Surg. Med. 48:866-877, 2016. © 2016 Wiley Periodicals, Inc.

Hyaline cartilage calcification of the first metatarsophalangeal joint is associated with osteoarthritis but independent of age and BMI.

BACKGROUND: Hyaline cartilage calcification (CC) is associated with osteoarthritis (OA) in hip and knee joints. The first metatarsophalangeal joint (1stMTPJ) is frequently affected by OA, but it is unclear if CC occurs in the 1stMTPJ. The aim of the present study was to analyze the prevalence of CC of the 1stMTPJ in the general population by high-resolution digital contact radiography (DCR) and to determine its association with histological OA severity, age and body mass index (BMI). METHODS: 168 metatarsal heads of 84 donors (n = 47 male, n = 37 female; mean age 62.73 years, SD ±18.8, range 20-93) were analyzed by DCR for the presence of CC. Histological OA grade (hOA) by OARSI was analyzed in the central load-bearing zone of the first metatarsal head (1st MH). Structural equation modeling (SEM) was performed to analyze the interrelationship between CC, hOA, age and BMI. RESULTS: The prevalence of CC of 1stMH was 48.8 % (41/84) (95 %-CI [37.7 %, 60.0 %]), independent of the affected side (p = 0.42), gender (p = 0.41) and BMI (p = 0.51). The mean amount of CC of one MH correlated significantly with that of the contralateral side (rs = 0.4, 95 %-CI [0.26, 0.52], p < 0.001). The mean amount of CC (in % of total cartilage area) of the MH correlated significantly with the severity of hOA (rs = 0.51, 95 %-CI [0.32, 0.65], p < 0.001). SEM revealed significant associations between CC and hOA (r = 0.74, p < 0.001) and between hOA and age (ß = 0.62, p = 0.001), but not between CC and age (p = 0.15). There was no significant influence of BMI on either CC (p = 0.37) or hOA (p = 0.16). CONCLUSION: The observation that CC of the 1stMH is significantly associated with the severity of OA but independent of age and BMI, suggests an intimate relationship between CC and the pathogenesis of OA, the exact nature of which will have to be explored by future studies.

Morphological and compositional monitoring of a new cell-free cartilage repair hydrogel technology - GelrinC by MR using semi-quantitative MOCART scoring and quantitative T2 index and new zonal T2 index calculation.

OBJECTIVE: To evaluate cartilage repair tissue (RT) using MOCART scoring for morphological and T2 mapping for biochemical assessment following implantation of GelrinC, a biosynthetic, biodegradable hydrogel implant. DESIGN: MR imaging (1.5/3T) was performed on 21 patients at six sites. Standard protocols were used for MOCART evaluation at 1 week (baseline) 1, 3, 6, 12, 18 and 24 months. Multi-echo SE was used for T2 mapping. Global (T2 in RT divided by T2 in normal cartilage) and zonal T2 index (deep T2 divided by superficial T2) of RT were calculated. RESULTS: Average MOCART score was 71.8 (95% CI 62.2 to 81.3) at six, 75.2 (95% CI 62.8 to 87.5) at twelve, 71.8 (95% CI 55.4 to 88.2) at eighteen and 84.4 (95% CI 77.7 to 91.0) at twenty-four months. The global T2 index ranged between 0.8 and 1.2 (normal healthy cartilage) in 1/11 (9%) patients at baseline, 8/12 (67%) at 12 months, 11/13 (85%) at 18 months and 13/16 (81%) at 24 months. The zonal T2 index for RT was <20% difference to the zonal T2 index for normal cartilage in: 6/12 patients (50%) at 12 months, 7/13 (53.8%) at 18 months and 10/16 (63.5%) at 24 months. The standard deviation for T2 showed a significant decrease over the study. CONCLUSIONS: The increase of MOCART scores over follow-up indicates improving cartilage repair tissue. Global and zonal T2 repair values at 24 months reached normal cartilage in 81% and 63.5% of the patients respectively, reflecting collagen organization similar to hyaline cartilage.

Brief report: reconstruction of joint hyaline cartilage by autologous progenitor cells derived from ear elastic cartilage.

In healthy joints, hyaline cartilage covering the joint surfaces of bones provides cushioning due to its unique mechanical properties. However, because of its limited regenerative capacity, age- and sports-related injuries to this tissue may lead to degenerative arthropathies, prompting researchers to investigate a variety of cell sources. We recently succeeded in isolating human cartilage progenitor cells from ear elastic cartilage. Human cartilage progenitor cells have high chondrogenic and proliferative potential to form elastic cartilage with long-term tissue maintenance. However, it is unknown whether ear-derived cartilage progenitor cells can be used to reconstruct hyaline cartilage, which has different mechanical and histological properties from elastic cartilage. In our efforts to develop foundational technologies for joint hyaline cartilage repair and reconstruction, we conducted this study to obtain an answer to this question. We created an experimental canine model of knee joint cartilage damage, transplanted ear-derived autologous cartilage progenitor cells. The reconstructed cartilage was rich in proteoglycans and showed unique histological characteristics similar to joint hyaline cartilage. In addition, mechanical properties of the reconstructed tissues were higher than those of ear cartilage and equal to those of joint hyaline cartilage. This study suggested that joint hyaline cartilage was reconstructed from ear-derived cartilage progenitor cells. It also demonstrated that ear-derived cartilage progenitor cells, which can be harvested by a minimally invasive method, would be useful for reconstructing joint hyaline cartilage in patients with degenerative arthropathies.