Terms Of Cartilage Repair Research Articles

An Injectable Enzymatically Crosslinked and Mechanically Tunable Silk Fibroin/Chondroitin Sulfate Chondro‐Inductive Hydrogel

AbstractAn injectable hybrid hydrogel is synthesized, comprising silk fibroin (SF) and chondroitin sulfate (CS) through di‐tyrosine formation bond of SF chains. CS and SF are reported with excellent biocompatibility as tissue engineering scaffolds. Nonetheless, the rapid degradation rate of pure CS scaffolds presents a challenge to effectively recreate articular cartilage. As CS is one of the cartilage extracellular matrix (ECM) components, it has the potential to enhance the biological activity of SF‐based hydrogel in terms of cartilage repair. Therefore, altering the CS concentrations (i.e., 0 wt%, 0.25 wt%, 0.5 wt%, 1 wt%, and 2 wt%), which are interpenetrated between SF β‐sheets and chains, can potentially adjust the physical, chemical, and mechanical features of these hybrid hydrogels. The formation of β‐sheets by 30 days of immersion in de‐ionized (DI) water can improve the compression strength of the SF/CS hybrid hydrogels in comparison with the same SF/CS hybrid hydrogels in the dried state. Biological investigation and observation depicts proper cell attachment, proliferation and cell viability for C28/I2 cells. Gene expression of sex‐determining region YBox 9 (SOX9), Collagen II α1, and Aggrecan (AGG) exhibits positive C3H10T1/2 growth and expression of cartilage‐specific genes in the 0.25 wt% and 0.5 wt% SF/CS hydrogels.

POS1126 CLINICAL EFFICACY AND SAFETY OF MONOCLONAL ANTIBODY AGAINST NERVE GROWTH FACTOR AND FIBROBLAST GROWTH FACTOR-18 THERAPY OF OSTEOARTHRITIS

BackgroundOsteoarthritis (OA) is the most common chronic progressive musculoskeletal system disease affecting more than 500 million people globally, which represents the formidable public health challenge. Currently osteoarthritis treatment includes acetaminophen, NSAIDs and/or opioids, intra-articular corticosteroid injections. Some guidelines also recommended chondroitin and glucosamine sulfate, suggested that they may be effective and reduce functional impairment. However, despite of the huge amount of data on the problem of OA, there is still no effective treatment that slows down the progression of the disease. Recently appeared monoclonal antibodies against nerve growth factor (NGF) as well as fibroblast growth factor (FGF)-18 may be the promising tool for clinical improvement of OAObjectivesTo evaluate the safety and efficacy of anti-NGF and FGF-18 on patients with osteoarthritis by a systematic review.MethodsIn the current study the search process was conducted in PubMed using the following strategy: “FGF-18” or “anti-NGF” and “OA”, “monoclonal antibody” + “osteoarthritis”. All articles published in the format of Case Reports, Clinical Study, Clinical Trial Protocol, Clinical Trial, Multicenter Study were reviewed. Clinical outcomes were assessed using clinical scores, included the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Pain and Physical Function score, Patient’s Global Assessment of OA (PGA-OA), adverse events (AEs); cartilage repair and total femorotibial joint cartilage thickness were assessed using magnetic resonance imaging.ResultsBased on our search 23 publication were included in the study after omitting repetitions. Among 23 studies, 16 used anti-NGF monoclonal antibodies (Tanezumab, Fasinumab, Fulranumab), and 7 used recombinant human FGF-18 (Sprifermin). The total of 6679 patients were analysed in these articles.In the pooled analysis NGF inhibitors demonstrated statistically significant improvements compared with placebo in WOMAC Pain and Physical Function score (all studies revealed significantly better clinical outcomes in the anti-NGF group). After treatment with FGF-18 (Sprifermin) there was also improvement in WOMAC scores though not statistically significant. However, FGF-18 therapy was associated with the reductions in loss of total and lateral femorotibial cartilage thickness. Moreover, it does not only significantly reduce cartilage loss but also increase cartilage thickness. In terms of cartilage repair, 5 of 7 studies reported improvement in total femorotibial joint cartilage thickness.The AEs of FGF-18 or anti-NGF therapies were not serious, however they may affect the compliance and satisfaction of patients and clinicians. The proportion of patients with adverse events in anti-NGF treatment group was higher than that in FGF-18. The following conditions were reported in anti-NGF: abnormal peripheral sensation such as hypoesthesia (7.43%), paraesthesia (9.15%), hyperesthesia (0.36%), peripheral neuropathy and sensory disturbance (0.35%); arthralgia (15%), back pain (15.06%), pain in extremity (10%), headache (9.11%), upper respiratory tract infection (10.65%), diarrhoea (11.95%), sinusitis or nasopharyngitis (10.13%). The difference in AEs between sprifermin and placebo groups was found insignificant, most frequently reported event was arthralgia.ConclusionIn recent years significant progress has been achieved in search for pathogenetic therapy of OA. Based on the results of current research findings, NGF inhibitors relieved pain and enhance joint function and may be considered as the most effective for functional improvement. FGF-18 decrease the cartilage loss and may improve cartilage thickness. However, further clinical longitudinal studies characterised the risk-benefit are needed to establish their safety and efficacy.Disclosure of InterestsNone declared

A Systematic Review of Focal Cartilage Defect Treatments in Middle-Aged Versus Younger Patients.

Background:Focal cartilage defects are often debilitating, possess limited potential for regeneration, are associated with increased risk of osteoarthritis, and are predictive for total knee arthroplasty. Cartilage repair studies typically focus on the outcome in younger patients, but a high proportion of treated patients are 40 to 60 years of age (ie, middle-aged). The reality of current clinical practice is that the ideal patient for cartilage repair is not the typical patient. Specific attention to cartilage repair outcomes in middle-aged patients is warranted.Purpose:To systematically review available literature on knee cartilage repair in middle-aged patients and include studies comparing results across different age groups.Study Design:Systematic review; Level of evidence, 4.Methods:A systematic search was performed in EMBASE, MEDLINE, and the Cochrane Library database. Articles were screened for relevance and appraised for quality.Results:A total of 21 articles (mean Coleman Methodology Score, 64 points) were included. Two out of 3 bone marrow stimulation (BMS) studies, including 1 using the microfracture technique, revealed inferior clinical outcomes in middle-aged patients in comparison with younger patients. Nine cell-based studies were included showing inconsistent comparisons of results across age groups for autologous chondrocyte implantation (ACI). Bone marrow aspirate concentrate showed age-independent results at up to 8 years of follow-up. A negative effect of middle age was reported in 1 study for both ACI and BMS. Four out of 5 studies on bone-based resurfacing therapies (allografting and focal knee resurfacing implants [FKRIs]) showed age-independent results up to 5 years. One study in only middle-aged patients reported better clinical outcomes for FKRIs when compared with biological repairs.Conclusion:Included studies were heterogeneous and had low methodological quality. BMS in middle-aged patients seems to only result in short-term improvements. More research is warranted to elucidate the ameliorating effects of cell-based therapies on the aging joint homeostasis. Bone-based therapies seem to be relatively insensitive to aging and may potentially result in effective joint preservation. Age subanalyses in cohort studies, randomized clinical trials, and international registries should generate more evidence for the large but underrepresented (in terms of cartilage repair) middle-aged population in the literature.

Efficacy and safety of intra-articular injection of mesenchymal stem cells in the treatment of knee osteoarthritis: A systematic review and meta-analysis.

Objective:To evaluate the effects and safety of intra-articular injection of mesenchymal stem cells on patients with knee osteoarthritis by a systematic review and meta-analysis.Methods:PubMed, EMBASE, and Cochrane Library were retrieved. An assessment of the risk of bias was done through the Cochrane Collaborative Bias Risk Tool, publication bias was assessed by plotting funnel plots and Egger tests. Pain and functional improvements in patients with knee osteoarthritis were determined by changes in VAS scores and WOMAC scores at baseline and follow-up endpoints. For the evaluation of MRI, the WORMS score and changes in cartilage volume were used. In addition, the number of adverse events in the intervention group and the control group were counted to explore the safety.Results:A total of 10 randomized controlled trials involving 335 patients were included. In the pooled analysis, compared with the control groups, the VAS scores of MSC groups decreased significantly (MD,−19.24; 95% CI: −26.31 to −12.18, P < .00001. All of the WOMAC scores also improved significantly: the total scores (SMD, − 0.66; 95% CI: − 1.09 to −0.23, P = .003), pain scores (SMD, − 0.46; 95% CI: − 0.75 to −0.17, P = .002), stiffness scores (SMD, −0.32; 95% CI: −0.64 to 0.00 P = 0.05), and functional scores (SMD, −0.36; 95% CI: −0.69 to −0.04, P = .03). Two studies with non-double-blind designs were the main source of heterogeneity. In terms of cartilage repair, there was no significant difference in the WORMS score, but there was a significant increase in cartilage volume in the MSC group (SMD, 0.69; 95% CI: 0.25 to 1.13, P = .002). The proportion of patients with adverse events in the MSCs treatment group was significantly higher than that in the control group (OR, 3.20; 95% CI: 1.50 to 6.83, P = .003).Conclusions:Intra-articular injection of mesenchymal stem cells is effective and safety to relieve pain and improve motor function of patients with knee osteoarthritis in a short term which is different to conclusions of previous study.

One-Stage Osteochondral Fracture Repair Technique With Knotless Anchors and Interconnected Crossing Suture Sliding Loops for the Knee

Osteochondral fractures of the knee represent a challenging entity to manage since there are many different surgical techniques for cartilage repair or other salvage procedures. In terms of cartilage repair, several hardware devices can be used, and many of them could imply a second-stage surgery for hardware removal. The purpose of this article is to describe in detail a one-stage osteochondral fracture repair technique with knotless anchors and interconnected crossing suture sliding loops for the knee. This technique is a one-stage open or arthroscopic procedure with an unlimited number of loops configurations with no particular need for a second surgery for hardware removal, no knot damage, and without the use of bone tunnels. It can be used in different cartilage anatomic locations, such as femoral condyles, trochlea, patella, or other joints.

Intra-articular mesenchymal stem cells for cartilage repair in osteoarthritis of the knee

Background & Aim Increasing numbers of clinical studies have addressed the use of mesenchymal stem cells (MSCs) for the treatment of osteoarthritis. However, the clinical benefit of MSCs for cartilage repair in osteoarthritis remains unclear. Although some recent studies reported the clinical benefits of intra-articular MSCs in the treatment of osteoarthritis, the clinical efficacy of MSCs in cartilage repair or cartilage protection in osteoarthritis has not been established. In addition, there is little consensus as which cell source, type of cell population, or delivery method should be used. Hence, this study aimed to provide a systematic review of the clinical literature supporting the efficacy of MSCs in terms of clinical outcomes and cartilage repair in patients with osteoarthritis and to strictly differentiate the various cell sources, types of cell populations, and delivery methods that have been used. Methods, Results & Conclusion Methods We systematically reviewed any studies investigating the clinical application of cell populations containing MSCs in human subjects with knee osteoarthritis through MEDLINE, EMBASE, the Cochrane Library, CINAHL, Web of Science, and Scopus. Studies with a level of evidence of IV or V were excluded. Methodological quality was assessed using the Modified Coleman Methodology Score. Clinical outcomes were assessed using clinical scores, and cartilage repair was assessed using MRI and second-look arthroscopy findings. Results A total of 17 studies that met the criteria were included in this review, with 6 randomized controlled trials, 8 prospective cohort studies, and 3 retrospective case-control studies. Among 17 studies, 8 studies used bone marrow-derived MSCs, 6 used adipose tissue-derived stromal vascular fraction, 2 used adipose tissue-derived MSCs, and 1 used umbilical cord blood-derived MSCs. All studies except 2 reported improvements in clinical outcomes. In terms of cartilage repair, 9 of 11 studies reported improvement of the cartilage state on MRI, and 6 of 7 studies reported repaired tissue on second-look arthroscopy. The mean Modified Coleman Methodology Score was 55.5±15.5 (range, 28-74). Conclusion Intra-articular MSCs seem to provide improvements in pain and function in knee osteoarthritis at short-term follow-up. However, the improvement was modest overall, and the effects of adjuvant treatment need to be clarified. Overall, evidence of the efficacy of MSCs for cartilage repair in osteoarthritis remains limited.