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Purpose The increasing awareness on the role of subchondral bone in the etiopathology of articular surface lesions led to the development of osteochondral scaffolds. While safety and promising results have been suggested, there are no trials proving the real potential of the osteochondral regenerative approach. Aim was to assess the benefit provided by a nanostructured collagen–hydroxyapatite (coll-HA) multilayer scaffold for the treatment of chondral and osteochondral knee lesions. Methods In this multicentre randomized controlled clinical trial, 100 patients affected by symptomatic chondral and osteochondral lesions were treated and evaluated for up to 2 years (51 study group and 49 control group). A biomimetic coll-HA scaffold was studied, and bone marrow stimulation (BMS) was used as reference intervention. Primary efficacy measurement was IKDC subjective score at 2 years. Secondary efficacy measurements were: KOOS, IKDC Knee Examination Form, Tegner and VAS Pain scores evaluated at 6, 12 and 24 months. Tissue regeneration was evaluated with MRI MOCART scoring system at 6, 12 and 24 months. An external independent agency was involved to ensure data correctness and objectiveness. Results A statistically significant improvement of all clinical scores was obtained from basal evaluation to 2-year follow-up in both groups, although no overall statistically significant differences were detected between the two treatments. Conversely, the subgroup of patients affected by deep osteochondral lesions (i.e. Outerbridge grade IV and OCD) showed a statistically significant better IKDC subjective outcome (+12.4 points, p  = 0.036) in the coll-HA group. Statistically significant better results were also found for another challenging group: sport active patients (+16.0, p  = 0.027). Severe adverse events related to treatment were documented only in three patients in the coll-HA group and in one in the BMS group. The MOCART score showed no statistical difference between the two groups. Conclusions This study highlighted the safety and potential of a biomimetic implant. While no statistically significant differences were found compared to BMS for chondral lesions, this procedure can be considered a suitable option for the treatment of osteochondral lesions. Level of evidence I.

Background Platelet Rich Plasma (PRP), a blood-derived product rich in growth factors, is a promising treatment for cartilage defects but there is still a lack of clinical evidence. The aim of this study is to show, through a randomized double blind prospective trial, the efficacy of this procedure, by comparing PRP to Hyaluronic Acid (HA) injections for the treatment of knee chondropathy or osteoarthritis (OA). Methods 109 patients (55 treated with HA and 54 with PRP) were treated and evaluated at 12 months of follow-up. The patients were enrolled according to the following inclusion criteria: age> 18 years, history of chronic (at least 4 months) pain or swelling of the knee and imaging findings of degenerative changes of the joint (Kellgren-Lawrence Score up to 3). A cycle of 3 weekly injections was administered blindly. All patients were prospectively evaluated before and at 2, 6, and 12 months after the treatment by: IKDC, EQ-VAS, TEGNER, and KOOS scores. Range of motion and knee circumference changes were measured over time. Adverse events and patient satisfaction were also recorded. Results Only minor adverse events were detected in some patients, such as mild pain and effusion after the injections, in particular in the PRP group, where a significantly higher post-injective pain reaction was observed (p=0.039). At the follow-up evaluations, both groups presented a clinical improvement but the comparison between the two groups showed a not statistically significant difference in all scores evaluated. A trend favorable for the PRP group was only found in patients with low grade articular degeneration (Kellgren-Lawrence score up to 2). Conclusions Results suggest that PRP injections offer a significant clinical improvement up to one year of follow-up. However, conversely to what was shown by the current literature, for middle-aged patients with moderate signs of OA, PRP results were not better than those obtained with HA injections, and thus it should not be considered as first line treatment. More promising results are shown for its use in low grade degeneration, but they still have to be confirmed.

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.

Background Full-thickness chondral defects and early osteoarthritis continue to present major challenges for the patient and the orthopaedic surgeon as a result of the limited healing potential of articular cartilage. The use of bioactive growth factors is under consideration as a potential therapy to enhance healing of chondral injuries and modify the arthritic disease process. Questions/purposes We reviewed the role of growth factors in articular cartilage repair and identified specific growth factors and combinations of growth factors that have the capacity to improve cartilage regeneration. Additionally, we discuss the potential use of platelet-rich plasma, autologous-conditioned serum, and bone marrow concentrate preparations as methods of combined growth factor delivery. Methods A PubMed search was performed using key words cartilage or chondrocyte alone and in combination with growth factor. The search was open for original manuscripts and review papers and open for all dates. From these searches we selected manuscripts investigating the effects of growth factors on extracellular matrix synthesis and excluded those investigating molecular mechanisms of action. Results By modulating the local microenvironment, the anabolic and anticatabolic effects of a variety of growth factors have demonstrated potential in both in vitro and animal studies of cartilage injury and repair. Members of the transforming growth factor-β superfamily, fibroblast growth factor family, insulin-like growth factor-I, and platelet-derived growth factor have all been investigated as possible treatment augments in the management of chondral injuries and early arthritis. Conclusions The application of growth factors in the treatment of local cartilage defects as well as osteoarthritis appears promising; however, further research is needed at both the basic science and clinical levels before routine application.

To investigate and compare the values of 3.0 T MRI T1, T2 and T2* mapping quantification techniques in evaluating cartilage degeneration of the shoulder joint. This study included 123 shoulder joints of 119 patients, which were scanned in 3.0 T MRI with axial Fat Suppression Proton Density Weighted Image (FS-PDWI), sagittal fat suppression T2 Weighted Image (FS-T2WI), coronal T1Weighted Image (T1WI), FS-PDWI, cartilage-specific T1, T2 and T2* mapping sequences. Basing on MRI images, the shoulder cartilage was classified into grades 0 1, 2, 3 and 4 according to the International Cartilage Regeneration & Joint Preservation Society (ICRS). The grading of shoulder cartilage was based on MRI images with ICRS as reference, and did not involve arthroscopy or histology.The T1, T2 and T2* relaxation values in the superior, middle and inferior bands of shoulder articular cartilage were measured at all grades, and the differences in various indicators between groups were analyzed and compared using a single-factor ANOVA test. The correlation between T1, T2 and T2* relaxation values and MRI-based grading was analyzed by SPSS software. There were 46 shoulder joints with MRI-based grade 0 in healthy control group (n = 46), while 49 and 28 shoulder joints with grade 1–2 (mild degeneration subgroup) and grade 3–4 (severe degeneration subgroup) in patient group (n = 73), accounting for 63.6% and 36.4%, respectively. The T1, T2 and T2* relaxation values of the superior, middle and inferior bands of shoulder articular cartilage were significantly and positively correlated with the MRI-based grading ( P  < 0.01). MRI-basedgrading of shoulder cartilage was markedly associated with age (r = 0.766, P  < 0.01). With the aggravation of cartilage degeneration, T1, T2 and T2* relaxation values showed an upward trend (all P  < 0.01), and T1, T2 and T2* mapping could distinguish cartilage degeneration at all levels (all P  < 0.01). The T1, T2 and T2* relaxation values were significantly different between normal group and mild degeneration subgroup, normal group and severe degeneration subgroup, mild degeneration subgroup and severe degeneration subgroup (all P  < 0.05). Quantitative T1, T2 and T2* mapping can quantify the degree of shoulder cartilage degeneration. All these MRI mapping quantification techniques can be used as critical supplementary sequences to assess shoulder cartilage degeneration, among which T2 mapping has the highest value.

Background Clinical cartilage restoration is evolving, with established and emerging technologies. Randomized, prospective studies with adequate power comparing the myriad of surgical techniques used to treat chondral injuries are still lacking and it remains a challenge for the surgeon treating patients to make evidence-based decisions. Questions/purposes We reviewed the history of the major cartilage repair/restorative procedures, indications for currently available repair/restorative procedures, and postoperative management. Methods We performed searches using MEDLINE and cartilage-specific key words to identify all English-language literature. Articles were selected based on their contributions to our current understanding of the basic science and clinical treatment of articular cartilage lesions or historical importance. We then selected 77 articles, two of which are articles of historical importance. Results Current cartilage restorative techniques include débridement, microfracture, osteochondral fragment repair, osteochondral allograft, osteochondral autograft, and autologous chondrocyte transplantation. Pending techniques include two-staged cell-based therapies integrated into a variety of scaffolds, single-stage cell-based therapy, and augmentation of marrow stimulation, each with suggested indications including lesion size, location, and activity demands of the patient. The literature demonstrates variable improvements in pain and function contingent upon multiple variables including indications and application. Conclusions For the patient with symptomatic chondral injury, numerous techniques are available to the surgeon to relieve pain and improve function. Until rigorous clinical trials (prospective, adequately powered, randomized control) are available, treatment decisions should be guided by expert extrapolation of the available literature based in historically sound principles.

Bone marrow lesions (BMLs) around the knee are a common magnetic resonance imaging (MRI) finding. However, despite the growing interest on BMLs in multiple pathological conditions, they remain controversial not only for the still unknown role in the etiopathological processes, but also in terms of clinical impact and treatment. The differential diagnosis includes a wide range of conditions: traumatic contusion and fractures, cyst formation and erosions, hematopoietic and infiltrated marrow, developmental chondroses, disuse and overuse, transient bone marrow oedema syndrome and, lastly, subchondral insufficiency fractures and true osteonecrosis. Regardless the heterogeneous spectrum of these pathologies, a key factor for patient management is the distinction between reversible and irreversible conditions. To this regard, MRI plays a major role, leading to the correct diagnosis based on recognizable typical patterns that have to be considered together with coexistent abnormalities, age, and clinical history. Several treatment options have been proposed, from conservative to surgical approaches. In this manuscript the main lesion patterns and their management have been analysed to provide the most updated evidence for the differential diagnosis and the most effective treatment. Level of evidence IV.

Objectives To assess whether partial meniscectomy is associated with increased risk of radiographic osteoarthritis (ROA) and worsening cartilage damage in the following year. Methods We studied 355 knees from the Osteoarthritis Initiative that developed ROA (Kellgren-Lawrence grade ≥ 2), which were matched with control knees. The MR images were assessed using the semi-quantitative MOAKS system. Conditional logistic regression was applied to estimate risk of incident ROA. Logistic regression was used to assess the risk of worsening cartilage damage in knees with partial meniscectomy that developed ROA. Results In the group with incident ROA, 4.4 % underwent partial meniscectomy during the year prior to the case-defining visit, compared with none of the knees that did not develop ROA. All ( n  = 31) knees that had partial meniscectomy and 58.9 % ( n  = 165) of the knees with prevalent meniscal damage developed ROA (OR = 2.51, 95 % CI [1.73, 3.64]). In knees that developed ROA, partial meniscectomy was associated with an increased risk of worsening cartilage damage (OR = 4.51, 95 % CI [1.53, 13.33]). Conclusions The probability of having had partial meniscectomy was higher in knees that developed ROA. When looking only at knees that developed ROA, partial meniscectomy was associated with greater risk of worsening cartilage damage. Key Points • Partial meniscectomy is a controversial treatment option for degenerative meniscal tears. • Partial meniscectomy is strongly associated with incident osteoarthritis within 1 year. • Partial meniscectomy is associated with increased risk of worsening cartilage damage.

There is increasing evidence that chondrocytes within articular cartilage are affected by endogenous force-related electrical potentials. Furthermore, electrical stimulation (ES) promotes the proliferation of chondrocytes and the synthesis of extracellular matrix (ECM) molecules, which accelerate the healing of cartilage defects. These findings suggest the potential application of ES in cartilage repair. In this review, we summarize the pathogenesis of articular cartilage injuries and the current clinical strategies for the treatment of articular cartilage injuries. We then focus on the application of ES in the repair of articular cartilage in vivo. The ES-induced chondrogenic differentiation of mesenchymal stem cells (MSCs) and its potential regulatory mechanism are discussed in detail. In addition, we discuss the potential of applying piezoelectric materials in the process of constructing engineering articular cartilage, highlighting the important advances in the unique field of tissue engineering.

Osteoarthritis (OA) is closely associated with aging, but its underlying mechanism is unclear. Recent publications were reviewed to elucidate the connection between aging and OA. With increasing OA incidence, more senior people are facing heavy financial and social burdens. Age-related OA pathogenesis is not well understood. Recently, it has been realized that age-related changes in other tissues besides articular cartilage may also contribute to OA development. Many factors including senescence-related secretory phenotypes, chondrocytes’ low reactivity to growth factors, mitochondrial dysfunction and oxidative stress, and abnormal accumulation of advanced glycation end products (AGEs) may all play key roles in the pathogenesis of age-related OA. Lately, epigenetic regulation of gene expression was recognized for its impact on age-related OA pathogenesis. Up to now, few studies have been reported about the role of miRNA and long-noncoding RNA (lncRNA) in age-related OA. Research focusing on this area may provide valuable insights into OA pathogenesis. OA-induced financial and social burdens have become an increasingly severe threat to older population. Age-related changes in noncartilage tissue should be incorporated in the understanding of OA development. Growing attention on oxidative stress and epigenetics will provide more important clues for the better understanding of the age-related OA.