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Nutrients Dec 2023Osteoarthritis (OA) is a degenerative joint disease that is age-related and progressive. It causes the destruction of articular cartilage and underlying bone, often... (Review)
Review
Osteoarthritis (OA) is a degenerative joint disease that is age-related and progressive. It causes the destruction of articular cartilage and underlying bone, often aggravated by inflammatory processes and oxidative stresses. This pathology impairs the quality of life of the elderly, causing pain, reduced mobility, and functional disabilities, especially in obese patients. Phytochemicals with anti-inflammatory and antioxidant activities may be used for long-term treatment of OA, either in combination with current anti-inflammatories and painkillers, or as an alternative to other products such as glucosamine and chondroitin, which improve cartilage structure and elasticity. The current systematic review provides a comprehensive understanding of the use of flavonoids. It highlights chondrocyte, cartilage, and subchondral bone activities, with a particular focus on their nutrigenomic effects. The molecular mechanisms of these molecules demonstrate how they can be used for the prevention and treatment of OA in the elderly population. However, clinical trials are still needed for effective use in clinical practice.
Topics: Aged; Humans; Cartilage, Articular; Flavonoids; Nutrigenomics; Osteoarthritis; Quality of Life
PubMed: 38201942
DOI: 10.3390/nu16010112 -
Bone & Joint Research Sep 2023Osteoarthritis (OA) is mainly caused by ageing, strain, trauma, and congenital joint abnormalities, resulting in articular cartilage degeneration. During the...
Osteoarthritis (OA) is mainly caused by ageing, strain, trauma, and congenital joint abnormalities, resulting in articular cartilage degeneration. During the pathogenesis of OA, the changes in subchondral bone (SB) are not only secondary manifestations of OA, but also an active part of the disease, and are closely associated with the severity of OA. In different stages of OA, there were microstructural changes in SB. Osteocytes, osteoblasts, and osteoclasts in SB are important in the pathogenesis of OA. The signal transduction mechanism in SB is necessary to maintain the balance of a stable phenotype, extracellular matrix (ECM) synthesis, and bone remodelling between articular cartilage and SB. An imbalance in signal transduction can lead to reduced cartilage quality and SB thickening, which leads to the progression of OA. By understanding changes in SB in OA, researchers are exploring drugs that can regulate these changes, which will help to provide new ideas for the treatment of OA.
PubMed: 37678837
DOI: 10.1302/2046-3758.129.BJR-2023-0081.R1 -
Journal of Orthopaedics Jan 2023The potential for cartilage repair using articular cartilage derived chondroprogenitors has recently gained popularity due to promising results from in-vitro and in-vivo... (Review)
Review
PURPOSE OF RESEARCH
The potential for cartilage repair using articular cartilage derived chondroprogenitors has recently gained popularity due to promising results from in-vitro and in-vivo studies. Translation of results from in-vitro to a clinical setting requires a sufficient number of animal studies displaying significant positive outcomes. Thus, this systematic review comprehensively discusses the available literature (January 2000-March 2022) on animal models employing chondroprogenitors for cartilage regeneration, highlighting the results and limitations associated with their use.As per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a web-based search of PubMed and SCOPUS databases was performed for the following terminologies: "chondroprogenitors", "cartilage-progenitors", and "chondrogenic-progenitors", which yielded 528 studies. A total of 12 studies met the standardized inclusion criteria, which included chondroprogenitors derived from hyaline cartilage isolated using fibronectin adhesion assay (FAA) or migratory assay from explant cultures, further analyzing the role of chondroprogenitors using in-vivo animal models.
PRINCIPAL RESULTS
Analysis revealed that FAA chondroprogenitors demonstrated the ability to attenuate osteoarthritis, repair chondral defects and form stable cartilage in animal models. They displayed better outcomes than bone marrow-derived mesenchymal stem cells but were comparable to chondrocytes. Migratory chondroprogenitors also demonstrated superiority to BM-MSCs in terms of higher chondrogenesis and lower hypertrophy, although a direct comparison to FAA-CPs and other cell types is warranted.
MAJOR CONCLUSIONS
Chondroprogenitors exhibit superior properties for chondrogenic repair; however, limited data on animal studies necessitates further studies to optimize their use before clinical translation for neo-cartilage formation.
PubMed: 36387762
DOI: 10.1016/j.jor.2022.10.012 -
Journal of Experimental Orthopaedics Nov 2023The aim of this systematic review was to analyse the available clinical evidence on intra-articular knee injections for the treatment of degenerative cartilage lesions... (Review)
Review
PURPOSE
The aim of this systematic review was to analyse the available clinical evidence on intra-articular knee injections for the treatment of degenerative cartilage lesions and osteoarthritis (OA) in sport-active patients.
METHODS
A literature search was performed in July 2023 according to the PRISMA guidelines on three electronic databases (PubMed, Cochrane, Web of Science). Studies addressing intra-articular injections for degenerative knee cartilage lesions or knee OA in sport-active patients were included. The Downs and Black's "checklist for measuring quality" was used to evaluate risk of bias and quality of the included studies.
RESULTS
Only 10 clinical studies for a total of 296 sport-active patients were included, with a publication trend increasing over time. The studies were 9 case series and 1 RCT; 7 studies focused on hyaluronic acid (HA), 2 studies focused on platelet-rich plasma (PRP), while 1 study compared HA and PRP. Overall, safety and positive clinical findings were for both HA and PRP, although not always with satisfactory results in terms of return to sport. The Downs and Black evaluation showed an overall poor quality of the included studies, with an average score of 21.1 points (range 19-25).
CONCLUSIONS
The available clinical evidence is still limited, with only a few studies published and an overall low-quality of evidence, suggesting a potential role of HA and PRP injections to treat these patients. However, further high-level trials are needed to confirm the real benefits of these treatments for the management of sport-active patients affected by degenerative cartilage lesions or OA of the knee.
PubMed: 37938446
DOI: 10.1186/s40634-023-00674-0 -
NPJ Regenerative Medicine Jan 2022Over the past two decades, evidence has emerged for the existence of a distinct population of endogenous progenitor cells in adult articular cartilage, predominantly... (Review)
Review
Over the past two decades, evidence has emerged for the existence of a distinct population of endogenous progenitor cells in adult articular cartilage, predominantly referred to as articular cartilage-derived progenitor cells (ACPCs). This progenitor population can be isolated from articular cartilage of a broad range of species, including human, equine, and bovine cartilage. In vitro, ACPCs possess mesenchymal stromal cell (MSC)-like characteristics, such as colony forming potential, extensive proliferation, and multilineage potential. Contrary to bone marrow-derived MSCs, ACPCs exhibit no signs of hypertrophic differentiation and therefore hold potential for cartilage repair. As no unique cell marker or marker set has been established to specifically identify ACPCs, isolation and characterization protocols vary greatly. This systematic review summarizes the state-of-the-art research on this promising cell type for use in cartilage repair therapies. It provides an overview of the available literature on endogenous progenitor cells in adult articular cartilage and specifically compares identification of these cell populations in healthy and osteoarthritic (OA) cartilage, isolation procedures, in vitro characterization, and advantages over other cell types used for cartilage repair. The methods for the systematic review were prospectively registered in PROSPERO (CRD42020184775).
PubMed: 35013329
DOI: 10.1038/s41536-021-00203-6 -
Disease Models & Mechanisms Jun 2018Articular cartilage defects may initiate osteoarthritis. Subchondral drilling, a widely applied clinical technique to treat small cartilage defects, does not yield... (Meta-Analysis)
Meta-Analysis Review
Articular cartilage defects may initiate osteoarthritis. Subchondral drilling, a widely applied clinical technique to treat small cartilage defects, does not yield cartilage regeneration. Various translational studies aiming to improve the outcome of drilling have been performed; however, a robust systematic analysis of its translational evidence was still lacking. Here, we performed a systematic review of the outcome of subchondral drilling for knee cartilage repair in translational animal models. A total of 12 relevant publications studying 198 animals was identified, detailed study characteristics were extracted, and methodological quality and risk of bias were analyzed. Subchondral drilling led to improved repair outcome compared with defects that were untreated or treated with abrasion arthroplasty for cartilage repair in multiple translational models. Within the 12 studies, considerable subchondral bone changes were observed, including subchondral bone cysts and intralesional osteophytes. Furthermore, extensive alterations of the subchondral bone microarchitecture appeared in a temporal pattern in small and large animal models, together with specific topographic aspects of repair. Moreover, variable technical aspects directly affected the outcomes of osteochondral repair. The data from this systematic review indicate that subchondral drilling yields improved short-term structural articular cartilage repair compared with spontaneous repair in multiple small and large animal models. These results have important implications for future investigations aimed at an enhanced translation into clinical settings for the treatment of cartilage defects, highlighting the importance of considering specific aspects of modifiable variables such as improvements in the design and reporting of preclinical studies, together with the need to better understand the underlying mechanisms of cartilage repair following subchondral drilling.
Topics: Animals; Arthroplasty, Subchondral; Cartilage, Articular; Publication Bias; Regeneration; Research Report; Risk Factors; Translational Research, Biomedical
PubMed: 29728409
DOI: 10.1242/dmm.034280 -
The Knee Oct 2023Autologous chondrocyte implantation (ACI) is primarily performed in active, young patients to treat knee pain and functional limitations resulting from articular... (Review)
Review
PURPOSE
Autologous chondrocyte implantation (ACI) is primarily performed in active, young patients to treat knee pain and functional limitations resulting from articular cartilage injury. Nevertheless, the functional outcomes of ACI remain poorly understood. This systematic review aimed to evaluate the biomechanical and functional outcomes of ACI.
METHODS
Ovid MEDLINE, Embase, and Web of Science were systematically searched using the terms 'Knee OR Knee joint AND Autologous chondrocyte implantation OR ACI'. Inclusion and exclusion criteria were used to screen publications by title, abstract, and full text. Study quality and bias were assessed by two reviewers. Means and standard deviations of all collected variables were calculated and presented in the review.
PROSPERO ID
CRD42021238768.
RESULTS
Nineteen articles including 20 ACI cohorts were included. In general, the average range of motion (ROM) improved with clinical (>5°) and statistical significance (p < 0.05) postoperatively: 130.5 ± 14.8° to 136.1 ± 10.2°. Knee strength significantly improved within the first two postoperative years but remained poorer than control groups at final follow-up. No statistical differences were found between ACI and control groups in their ability to perform functional activities like the 6-minute walk test.
CONCLUSION
Knee range of motion generally improved following ACI. Although, some studies reported that knee strengths remained significantly poorer than healthy controls, particularly >2-years postoperatively, implying that longer-term strength training may benefit patients.However, the volume of research and current level of evidence remain low, thus further research is required to better understand the impact of ACI on knee function and guide future rehabilitative protocols.
Topics: Humans; Cartilage, Articular; Chondrocytes; Transplantation, Autologous; Knee Joint; Cartilage Diseases
PubMed: 37516029
DOI: 10.1016/j.knee.2023.07.004 -
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