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Advanced Science (Weinheim,... May 2022The osteochondral (OC) unit plays a pivotal role in joint lubrication and in the transmission of constraints to bones during movement. The OC unit does not spontaneously... (Review)
Review
The osteochondral (OC) unit plays a pivotal role in joint lubrication and in the transmission of constraints to bones during movement. The OC unit does not spontaneously heal; therefore, OC defects are considered to be one of the major risk factors for developing long-term degenerative joint diseases such as osteoarthritis. Yet, there is currently no curative treatment for OC defects, and OC regeneration remains an unmet medical challenge. In this context, a plethora of tissue engineering strategies have been envisioned over the last two decades, such as combining cells, biological molecules, and/or biomaterials, yet with little evidence of successful clinical transfer to date. This striking observation must be put into perspective with the difficulty in comparing studies to identify overall key elements for success. This systematic review aims to provide a deeper insight into the field of material-assisted strategies for OC regeneration, with particular considerations for the therapeutic potential of the different approaches (with or without cells or biological molecules), and current OC regeneration evaluation methods. After a brief description of the biological complexity of the OC unit, the recent literature is thoroughly analyzed, and the major pitfalls, emerging key elements, and new paths to success are identified and discussed.
Topics: Biocompatible Materials; Bone and Bones; Cartilage, Articular; Tissue Engineering; Tissue Scaffolds
PubMed: 35322596
DOI: 10.1002/advs.202200050 -
Cartilage Jan 2021Treatment of chondral injury is clinically challenging. Available chondral repair/regeneration techniques have significant shortcomings. A viable and durable tissue...
OBJECTIVE
Treatment of chondral injury is clinically challenging. Available chondral repair/regeneration techniques have significant shortcomings. A viable and durable tissue engineering strategy for articular cartilage repair remains an unmet need. Our objective was to systematically evaluate the published data on bioprinted articular cartilage with regards to scaffold-based, scaffold-free and cartilage bioprinting.
DESIGN
We performed a systematic review of studies using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed and ScienceDirect databases were searched and all articles evaluating the use of 3-dimensional (3D) bioprinting in articular cartilage were included. Inclusion criteria included studies written in or translated to English, published in a peer-reviewed journal, and specifically discussing bioinks and/or bioprinting of living cells related to articular cartilage applications. Review papers, articles in a foreign language, and studies not involving bioprinting of living cells related to articular cartilage applications were excluded.
RESULTS
Twenty-seven studies for articular cartilage bioprinting were identified that met inclusion and exclusion criteria. The technologies, materials, cell types used in these studies, and the biological and physical properties of the created constructs have been demonstrated.
CONCLUSION
These 27 studies have demonstrated 3D bioprinting of articular cartilage to be a tissue engineering strategy that has tremendous potential translational value. The unique abilities of the varied techniques allow replication of mechanical properties and advances toward zonal differentiation. This review demonstrates that bioprinting has great capacity for clinical cartilage reconstruction and future implantation.
Topics: Arthroplasty, Subchondral; Bioprinting; Cartilage, Articular; Female; Humans; Male; Printing, Three-Dimensional; Tissue Engineering; Tissue Scaffolds
PubMed: 30373384
DOI: 10.1177/1947603518809410 -
Journal of Clinical Medicine Oct 2023Osteoarthritis (OA) is one of the most common chronic diseases in the world. It is frequently accompanied by high levels of persistent pain, as well as substantial... (Review)
Review
PURPOSE
Osteoarthritis (OA) is one of the most common chronic diseases in the world. It is frequently accompanied by high levels of persistent pain, as well as substantial impairments in function and functional capacity. This review aims to systematically analyze the changes in proprioception and related mechanoreceptors in OA patients.
METHODS
Studies from September 2013 to September 2023 were identified by conducting searches on the PubMed, Web of Science, and Scopus electronic databases following the PRISMA statement. One reviewer independently assessed and screened the literature, extracted the data, and graded the studies. The body of evidence underwent an evaluation and grading process using the ROBINS-I tool, which was specifically designed to assess the risk of bias in non-randomized studies of interventions. Results were summarized using descriptive methods.
RESULTS
A search through 37 studies yielded 14 clinical studies that were ultimately included. The primary focus of the studies was on the knee joint, particularly the posterior cruciate ligament (PCL). The studies found that PCL in OA patients had impaired proprioceptive accuracy, possibly due to changes in mechanoreceptors (Ruffini, Pacini, and Golgi Mazzoni corpuscles). This suggests that dysfunctional articular mechanoreceptors, especially in severe cases of OA, may contribute to reduced proprioception. Dynamic stabilometry also identified significant proprioceptive deficits in patients with knee articular cartilage lesions, underscoring the impact of such lesions on knee proprioception.
CONCLUSIONS
Literature data have shown that proprioceptive accuracy may play an important role in OA, particularly in the knee PCL and cartilage. However, the role of proprioception and related mechanoreceptors needs to be further clarified. Future studies focusing on the relationship between proprioception, OA disease, and symptoms, considering age and gender differences, and exploring OA joints other than the knee should be conducted to improve clinical and surgical outcomes in cases where proprioception and mechanoreceptors are impaired in OA patients.
PubMed: 37892761
DOI: 10.3390/jcm12206623 -
Orthopaedic Journal of Sports Medicine Mar 2020The process of returning to work after cartilage treatment has not been studied in depth, even though a better understanding of potential outcomes could lead to... (Review)
Review
BACKGROUND
The process of returning to work after cartilage treatment has not been studied in depth, even though a better understanding of potential outcomes could lead to significant benefits for the general population.
PURPOSE
To determine which surgical interventions are most effective in helping patients return to work after cartilage repair and to identify factors that affect the ability to return to work.
STUDY DESIGN
Systematic review; Level of evidence, 4.
METHODS
This systematic review followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines in analyzing reports on articular cartilage treatment and return to work published from January 1966 (when the first system of classifying articular cartilage injuries based on the mechanism of injuries and type of lesions was developed) to January 2019. General surgical information and available clinical scores were used to assess outcomes.
RESULTS
Only 5 studies describing 283 patients were found to be relevant to our objectives and were therefore included in the analysis. Autologous chondrocyte implantation (ACI) and osteochondral allografts were the only 2 procedures for which information was included regarding patient return to work rates. The mean (overall) return-to-work time after a cartilage repair operation was 4.80 ± 3.02 months. ACI was the most common procedure (3 studies; 227 patients). Return to work after ACI or ACI with high tibial osteotomy (HTO) occurred in almost 100% of cases, whereas the rate of return to work was 51.78% for patients who underwent osteochondral allograft ( < .01); further, patients who had ACI or ACI+HTO returned to work sooner compared with patients who underwent osteochondral allograft. The Knee injury and Osteoarthritis Outcome Score (KOOS) and Single Assessment Numerical Evaluation (SANE) scores were significantly higher in patients who fully returned to work. No significant difference was found in rates of return to work after ACI related to sex, area of the lesion, or size of the defect.
CONCLUSION
The vast majority of published results on articular cartilage repair do not include data on return to work. Although available data on articular cartilage repair in the general population reveal a high rate of return to work, including those patients treated with ACI, the data do not stratify patients by the type and demand of work. No randomized studies have examined return-to-work rates. Hence, authors should include these data in future studies. A refined definition of work intensity, rather than just return to work, may provide a clearer picture of the relative effectiveness of different surgical interventions. To that end, the authors propose a return to work prognostic score called the Prognostic Cartilage Repair Return to Work Score, or PROCART-RTW score.
PubMed: 32206672
DOI: 10.1177/2325967120905526 -
BMC Musculoskeletal Disorders May 2023To systematically review the studies regarding to the safety, efficacy and application methods of PRP in promoting the talar cartilage repair. (Meta-Analysis)
Meta-Analysis
PURPOSE
To systematically review the studies regarding to the safety, efficacy and application methods of PRP in promoting the talar cartilage repair.
METHODS
A systematic review was performed by searching PubMed, Web of Science, OVID and EMBASE to identify studies that compared the clinical efficacy of PRP for talar cartilage repair. Main outcome was the American Orthopedic Foot and Ankle Society (AOFAS) score for function and Visual Analog Scale (VAS) for pain was the second outcome.
RESULTS
A total of 10 studies were included in this systematic review, including 4 randomized controlled trials, 1 controlled trial, 3 case series and 2 cohort studies. Four RCTs were analyzed using meta-analysis. For all outcomes, statistical results favored PRP group (AOFAS: MD = 7.84; 95% CI= [-0.13, 15.80], I = 83%, P < 0.01; VAS: MD = 1.86; 95% CI= [0.68, 3.04], I = 85%, P < 0.01). There were almost no reports of adverse events related to PRP intervention. Subgroup analysis showed that whether PRP was used alone or combined with other treatments could result in high heterogeneity but no more specific factors were identified to contribute to this.
CONCLUSION
PRP is safe and effective for talar cartilage repair. In addition to the standardization of PRP preparation and application, it is necessary to distinguish the effects of PRP used alone or in combination with other treatments. In PRP studies, surgical treatment of talar cartilage repair remains the mainstream. The regulation of PRP in surgical applications are worth exploring. The most relative component is the mesenchymal stem cell because it is the only exposed chondrocyte precursor in the articular cavity whether it is microfracture or cell transplantation.
TRIAL REGISTRATION
The study was registered in the PROSPERO International prospective register of systematic reviews (CRD42022360183).
Topics: Humans; Chondrocytes; Fractures, Stress; Joints; Platelet-Rich Plasma; Cartilage; Randomized Controlled Trials as Topic
PubMed: 37161527
DOI: 10.1186/s12891-023-06466-y -
Frontiers in Immunology 2022Psoriatic arthritis (PsA) is a chronic inflammatory disease that frequently develops in patients with psoriasis (PsO) but can also occur spontaneously. As a result, PsA... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Psoriatic arthritis (PsA) is a chronic inflammatory disease that frequently develops in patients with psoriasis (PsO) but can also occur spontaneously. As a result, PsA diagnosis and treatment is commonly delayed, or even missed outright due to the manifold of clinical presentations that patients often experience. This inevitably results in progressive articular damage to axial and peripheral joints and entheses. As such, patients with PsA frequently experience reduced expectancy and quality of life due to disability. More recently, research has aimed to improve PsA diagnosis and prognosis by identifying novel disease biomarkers.
METHODS
Here, we conducted a systematic review of the published literature on candidate biomarkers for PsA diagnosis and prognosis in MEDLINE(Pubmed), EMBase and the Cochrane library with the goal to identify clinically applicable PsA biomarkers. Meta-analyses were performed when a diagnostic bone and cartilage turnover biomarker was reported in 2 or moredifferent cohorts of PsA and control.
RESULTS
We identified 1444 publications and 124 studies met eligibility criteria. We highlighted bone and cartilage turnover biomarkers, genetic markers, and autoantibodies used for diagnostic purposes of PsA, as well as acute phase reactant markers and bone and cartilage turnover biomarkers for activity or prognostic severity purposes. Serum cartilage oligometrix metalloproteinase levels were significantly increased in the PsA sera compared to Healthy Control (HC) with a standardized mean difference (SMD) of 2.305 (95%CI 0.795-3.816, p=0.003) and compared to osteoarthritis (OA) with a SMD of 0.783 (95%CI 0.015-1.551, p=0.046). The pooled serum MMP-3 levels were significantly higher in PsA patients than in PsO patients with a SMD of 0.419 (95%CI 0.119-0.719; p=0.006), but no significant difference was highlighted when PsA were compared to HC. While we did not identify any new genetic biomarkers that would be useful in the diagnosis of PsA, recent data with autoantibodies appear to be promising in diagnosis, but no replication studies have been published.
CONCLUSION
In summary, no specific diagnostic biomarkers for PsA were identified and further studies are needed to assess the performance of potential biomarkers that can distinguish PsA from OA and other chronic inflammatory diseases.
Topics: Humans; Arthritis, Psoriatic; Quality of Life; Biomarkers; Psoriasis; Autoantibodies; Osteoarthritis
PubMed: 36532039
DOI: 10.3389/fimmu.2022.1054539 -
Medicina (Kaunas, Lithuania) Dec 2022Background and Objectives: Human umbilical-cord-blood-derived mesenchymal stem cells (hUCB-MSCs) have recently been used in clinical cartilage regeneration procedures... (Meta-Analysis)
Meta-Analysis Review
Background and Objectives: Human umbilical-cord-blood-derived mesenchymal stem cells (hUCB-MSCs) have recently been used in clinical cartilage regeneration procedures with the expectation of improved regeneration capacity. However, the number of studies using hUCB-MSCs is still insufficient, and long-term follow-up results after use are insufficient, indicating the need for additional data and research. We have attempted to prove the efficacy and safety of hUCB-MSC treatment in a comprehensive analysis by including all subjects with knee articular cartilage defect or osteoarthritis who have undergone cartilage repair surgery using hUCB-MSCs. We conducted a meta-analysis and demonstrated efficacy and safety based on a systematic review. Materials and Methods: This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. For this study, we searched the PubMed, Embase, Web of Science, Scopus, and Cochrane Library literature databases up to June 2022. A total of seven studies were included, and quality assessment was performed for each included study using the Newcastle−Ottawa Quality Assessment Scale. Statistical analysis was performed on the extracted pooled clinical outcome data, and subgroup analyses were completed. Results: A total of 570 patients were included in the analysis. In pooled analysis, the final follow-up International Knee Documentation Committee (IKDC) score showed a significant increase (mean difference (MD), −32.82; 95% confidence interval (CI), −38.32 to −27.32; p < 0.00001) with significant heterogeneity (I2 = 93%, p < 0.00001) compared to the preoperative score. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores at final follow-up were significantly decreased (MD, 30.73; 95% CI, 24.10−37.36; p < 0.00001) compared to the preoperative scores, with significant heterogeneity (I2 = 95%, p < 0.00001). The visual analog scale (VAS) score at final follow-up was significantly decreased (MD, 4.81; 95% CI, 3.17−6.46; p < 0.00001) compared to the preoperative score, with significant heterogeneity (I2 = 98%, p < 0.00001). Two studies evaluated the modified Magnetic Resonance Observation of Cartilage Repair Tissue (M-MOCART) score and confirmed sufficient improvement. In a study analyzing a group treated with bone marrow aspiration concentrate (BMAC), there was no significant difference in clinical outcome or M-MOCART score, and the post-treatment International Cartilage Repair Society (ICRS) grade increased. Conclusion: This analysis demonstrated the safety, efficacy, and quality of repaired cartilage following hUCB-MSC therapy. However, there was no clear difference in the comparison with BMAC. In the future, comparative studies with other stem cell therapies or cartilage repair procedures should be published to support the superior effect of hUCB-MSC therapy to improve treatment of cartilage defect or osteoarthritis.
Topics: Humans; Osteoarthritis, Knee; Fetal Blood; Mesenchymal Stem Cell Transplantation; Cartilage, Articular; Mesenchymal Stem Cells; Arthroscopy; Treatment Outcome
PubMed: 36557003
DOI: 10.3390/medicina58121801 -
Orthopaedic Journal of Sports Medicine Sep 2020A 3-dimensional, scaffold-free, and completely autologous form of chondrocyte transplantation (ACT3D) has been developed and applied in clinical practice in the past... (Review)
Review
BACKGROUND
A 3-dimensional, scaffold-free, and completely autologous form of chondrocyte transplantation (ACT3D) has been developed and applied in clinical practice in the past decade to overcome disadvantages of previous-generation procedures.
PURPOSE
To document and analyze the available literature on the results of ACT3D in the treatment of articular chondral lesions in the knee and hip joints.
STUDY DESIGN
Systematic review; Level of evidence, 4.
METHODS
All studies published in English addressing ACT3D were identified and included those that fulfilled the following criteria: (1) level 1 through 4 evidence, (2) measures of radiological or functional/clinical outcome, and (3) outcome related to cartilage lesions of the knee and hip joints.
RESULTS
A total of 10 studies were selected: 2 randomized controlled trials, 1 cohort study, and 7 case series. The studies revealed significant increases in patients' subjective quality of life, satisfaction, pain reduction, and improvement in joint function at short- to medium-term follow-up. Magnetic resonance imaging-assisted examination and second-look arthroscopy showed a hyaline-like repair tissue with a high degree of defect filling and integration.
CONCLUSION
ACT3D shows promising results in the therapy of articular cartilage defects in the knee as well as in the hip, but well-designed, long-term studies are lacking. ACT3D might have relevant advantages over common matrix-associated autologous chondrocyte transplantation products, but systematic evaluation and randomized controlled studies are crucial to verify the potential of this tissue-engineered approach.
PubMed: 33015211
DOI: 10.1177/2325967120951152 -
Arthritis Research & Therapy Jan 2023Osteoarthritis (OA) is a common and prevalent degenerative joint disease characterized by degradation of the articular cartilage. However, none of disease-modifying OA... (Review)
Review
Osteoarthritis (OA) is a common and prevalent degenerative joint disease characterized by degradation of the articular cartilage. However, none of disease-modifying OA drugs is approved currently. Teriparatide (PTH (1-34)) might stimulate chondrocyte proliferation and cartilage regeneration via some uncertain mechanisms. Relevant therapies of PTH (1-34) on OA with such effects have recently gained increasing interest, but have not become widespread practice. Thus, we launch this systematic review (SR) to update the latest evidence accordingly. A comprehensive literature search was conducted in PubMed, Web of Science, MEDLINE, the Cochrane Library, and Embase from their inception to February 2022. Studies investigating the effects of the PTH (1-34) on OA were obtained. The quality assessment and descriptive summary were made of all included studies. Overall, 307 records were identified, and 33 studies were included. In vivo studies (n = 22) concluded that PTH (1-34) slowed progression of OA by alleviating cartilage degeneration and aberrant remodeling of subchondral bone (SCB). Moreover, PTH (1-34) exhibited repair of cartilage and SCB, analgesic, and anti-inflammatory effects. In vitro studies (n = 11) concluded that PTH (1-34) was important for chondrocytes via increasing the proliferation and matrix synthesis but preventing apoptosis or hypertrophy. All included studies were assessed with low or unclear risk of bias in methodological quality. The SR demonstrated that PTH (1-34) could alleviate the progression of OA. Moreover, PTH (1-34) had beneficial effects on osteoporotic OA (OPOA) models, which might be a therapeutic option for OA and OPOA treatment.
Topics: Humans; Teriparatide; Osteoarthritis; Cartilage, Articular; Chondrocytes; Hypertrophy
PubMed: 36609338
DOI: 10.1186/s13075-022-02981-w -
International Journal of Molecular... Oct 2023Mesenchymal stem cell (MSC)-based exosomes have garnered attention as a viable therapeutic for post-traumatic cartilage injury and osteoarthritis of the knee; however,... (Review)
Review
Mesenchymal stem cell (MSC)-based exosomes have garnered attention as a viable therapeutic for post-traumatic cartilage injury and osteoarthritis of the knee; however, efforts for application have been limited due to issues with variable dosing and rapid clearance in vivo. Scaffolds laden with MSC-based exosomes have recently been investigated as a solution to these issues. Here, we review in vivo studies and highlight key strengths and potential clinical uses of exosome-scaffold therapeutics for treatment of post-traumatic cartilage injury and osteoarthritis. In vivo animal studies were gathered using keywords related to the topic, revealing 466 studies after removal of duplicate papers. Inclusion and exclusion criteria were applied for abstract screening and full-text review. Thirteen relevant studies were identified for analysis and extraction. Three predominant scaffold subtypes were identified: hydrogels, acellular extracellular matrices, and hyaluronic acid. Each scaffold-exosome design showcased unique properties with relation to gross findings, tissue histology, biomechanics, and gene expression. All designs demonstrated a reduction in inflammation and induction of tissue regeneration. The results of our review show that current exosome-scaffold therapeutics demonstrate the capability to halt and even reverse the course of post-traumatic cartilage injury and osteoarthritis. While this treatment modality shows incredible promise, future research should aim to characterize long-term biocompatibility and optimize scaffold designs for human treatment.
Topics: Animals; Humans; Osteoarthritis, Knee; Exosomes; Cartilage Diseases; Knee Joint; Cartilage; Cartilage, Articular; Tissue Scaffolds
PubMed: 37894859
DOI: 10.3390/ijms242015178