Recent Advances in Osteoarthritis Management and Regenerative Strategies

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Orthopedics".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 36324

Special Issue Editors


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Guest Editor
IRCCS, Istituto Ortopedico Rizzoli, Laboratorio RAMSES, 40136 Bologna, Italy
Interests: osteoarthritis; musculoskeletal pathologies; cell-based therapies; mesenchymal stromal cells; ortho biological systems; 3D bioprinting; regenerative medicine

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Guest Editor
IRCCS, Istituto Ortopedico Rizzoli, Laboratorio RAMSES, 40136 Bologna, Italy
Interests: osteoarthritis; osteochondral repair; synovium; mesenchymal stromal cells; tissue engineering; immunohistochemical analyses and animal models

Special Issue Information

Dear Colleagues,

Osteoarthritis (OA) is one of the leading musculoskeletal diseases worldwide, with an enormous impact on patients’ daily life together with high costs for the health care system. Preclinical and clinical investigations showed the multi-coloured nature of OA based on complex molecular and cellular changes in the osteochondral unit, synovial membrane and meniscus. Cell-based therapies and other regenerative options showed promising effects in targeting molecular pathways involved in OA. Despite several advances in the last decades, many unsolved questions (e.g., cells versus no cells; optimal cell source and dosage; best delivery route; autologous versus allogenic treatment; etc.) remain challenging, leading to a lack of specific long-term therapies. Thus, there is a compelling demand for establishing new and mini-invasive treatment modalities to counteract OA evolution.

This special issue will give evidence on the progress of the state-of-the-art for OA care by outlining recent scientific updates for boosting clinical translation. We invite authors to propose original research and review articles, communications, and concept papers highlighting preclinical and clinical advances on relevant pathophysiological processes, models and therapeutic options to improve success in OA care. Potential topics include, but are not limited to:

  • novel concepts on the crosstalk among joint tissue in OA setting;
  • recent updates of the role of the synovial milieu on cartilage repair;
  • recognition of new targets and biomarkers (e.g., extracellular vesicles, cytokines) as diagnostic tools;
  • identification of peculiar and reliable in vitro and in vivo models mimicking OA microenvironment;
  • preclinical studies estimating the regenerative capacity of original approaches;
  • clinical studies presenting therapeutic procedures or personalized strategies for OA management.

Dr. Brunella Grigolo
Dr. Giovanna Desando
Guest Editors

Manuscript Submission Information

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Keywords

  • Osteoarthritis
  • Osteochondral repair
  • Synovial membrane
  • Inflammation
  • Hypertrophy
  • Oxidative stress
  • Cell-based therapy
  • Tissue engineering
  • 3D printing

Published Papers (13 papers)

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Research

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10 pages, 2451 KiB  
Article
Bevacizumab Arrests Osteoarthritis Progression in a Rabbit Model: A Dose-Escalation Study
by Gianluca Vadalà, Luca Ambrosio, Caterina Cattani, Roberta Bernardini, Antonino Giacalone, Rocco Papalia and Vincenzo Denaro
J. Clin. Med. 2021, 10(13), 2825; https://doi.org/10.3390/jcm10132825 - 26 Jun 2021
Cited by 8 | Viewed by 1606
Abstract
Cartilage neoangiogenesis holds a prominent role in osteoarthritis (OA) pathogenesis. This study aimed to assess the efficacy bevacizumab, an antibody against vascular endothelial growth factor and inhibitor of angiogenesis, in a rabbit OA model. Animals were divided into four groups: one receiving a [...] Read more.
Cartilage neoangiogenesis holds a prominent role in osteoarthritis (OA) pathogenesis. This study aimed to assess the efficacy bevacizumab, an antibody against vascular endothelial growth factor and inhibitor of angiogenesis, in a rabbit OA model. Animals were divided into four groups: one receiving a sham intra-articular knee injection and three groups undergoing 5, 10, and 20 mg intra-articular bevacizumab injections. The effect of the antibody on articular cartilage and synovium was assessed through histology and quantified with the Osteoarthritis Research Society International (OARSI) scores. Immunohistochemistry was performed to investigate type 2 collagen, aggrecan, and matrix metalloproteinase 13 (MMP-13) expression. Bevacizumab treatment led to a significant reduction of cartilage degeneration and synovial OA changes. Immunohistochemistry revealed significantly lower cartilage MMP-13 expression levels in all experimental groups, with the one receiving 20 mg bevacizumab showing the lowest. The antibody also resulted in increased production of aggrecan and type 2 collagen after administration of 5, 10, and 20 mg. The group treated with 20 mg showed the highest levels of type 2 collagen, while aggrecan content was even higher than in the healthy cartilage. Intra-articular bevacizumab has been demonstrated to effectively arrest OA progression in our model, with 20 mg being the most efficacious dose. Full article
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8 pages, 1210 KiB  
Article
Clinical Radiographical Outcomes and Complications after a Brand-New Total Ankle Replacement Design through an Anterior Approach: A Retrospective at a Short-Term Follow Up
by Massimiliano Mosca, Silvio Caravelli, Emanuele Vocale, Simone Massimi, Davide Censoni, Marco Di Ponte, Mario Fuiano and Stefano Zaffagnini
J. Clin. Med. 2021, 10(11), 2258; https://doi.org/10.3390/jcm10112258 - 23 May 2021
Cited by 5 | Viewed by 1887
Abstract
Recently, the progress in techniques and in projecting new prosthetic designs has allowed increasing indications for total ankle replacement (TAR) as treatment for ankle osteoarthritis. This retrospective work comprehended 39 subjects aged between 47 and 79 years old. The patients, observed for at [...] Read more.
Recently, the progress in techniques and in projecting new prosthetic designs has allowed increasing indications for total ankle replacement (TAR) as treatment for ankle osteoarthritis. This retrospective work comprehended 39 subjects aged between 47 and 79 years old. The patients, observed for at least 12 months (mean follow up of 18.2 ± 4.1 months), have been evaluated according to clinical and radiological parameters, both pre- and post-operatively. The AOFAS and VAS score significantly improved, respectively, from 46.2 ± 4.8 to 93.9 ± 4.1 and from 7.1 ± 1.1 to 0.7 ± 0.5 (p value < 0.05). At the final evaluation, the mean plantarflexion passed from 12.2° ± 2.3° to 18.1° ± 2.4° (p value < 0.05) and dorsiflexion from a pre-operative mean value of 8.7° ± 4.1° to 21.7° ± 5.4° post-operatively (p value < 0.05). This study found that this new total ankle replacement design is a safe and effective procedure for patients effected by end-stage ankle osteoarthritis. Improvements have been demonstrated in terms of range of motion, radiographic parameters and patient-reported outcomes. However, further studies are needed to assess the long-term performance of these prostheses. Full article
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14 pages, 2361 KiB  
Article
Autologous Micro-Fragmented Adipose Tissue (MFAT) to Treat Symptomatic Knee Osteoarthritis: Early Outcomes of a Consecutive Case Series
by Wouter Van Genechten, Kristien Vuylsteke, Pedro Rojas Martinez, Linus Swinnen, Kristof Sas and Peter Verdonk
J. Clin. Med. 2021, 10(11), 2231; https://doi.org/10.3390/jcm10112231 - 21 May 2021
Cited by 15 | Viewed by 2722
Abstract
The study aimed to evaluate the short-term clinical effect, therapeutic response rate (TRR%), and therapy safety of a single intra-articular autologous MFAT injection for symptomatic knee OA. Secondly, patient- and pathology-related parameters were investigated to tighten patient selection for MFAT therapy. Sixty-four subjects [...] Read more.
The study aimed to evaluate the short-term clinical effect, therapeutic response rate (TRR%), and therapy safety of a single intra-articular autologous MFAT injection for symptomatic knee OA. Secondly, patient- and pathology-related parameters were investigated to tighten patient selection for MFAT therapy. Sixty-four subjects with symptomatic mild–severe knee OA were enrolled in a single-center trial and received a unilateral (n = 37) or bilateral (n = 27) MFAT injection. After liposuction, the adipose tissue was mechanically processed with the Lipogem® device, which eventually produced 8–10 cc of MFAT. Subjects were clinically assessed by means of the KOOS, NRS, UCLA, and EQ-5D at baseline and 1, 3, 6, and 12 months after injection. Adverse events were recorded at each follow-up timepoint. The TRR was defined according to the OMERACT-OARSI criteria and baseline MRI was scored following the MOAKS classification. The TRR of the index knee was 64% at 3 months and 45% at 12 months after injection. Therapy responders at 12 months improved with 28.3 ± 11.4 on KOOS pain, while non-responders lost −2.1 ± 11.2 points. All clinical scores, except the UCLA, improved significantly at follow-up compared to baseline (p < 0.05). In the bilateral cohort, no difference in baseline scores or TRR was found between the index knee and contralateral knee (n.s.). An inflammatory reaction was reported in 79% of knees and resolved spontaneously within 16.6 ± 13.5 days after MFAT administration. Numerous bone marrow lesions (BML) were negatively correlated with the TRR at 12 months (p = 0.003). The study demonstrated an early clinical improvement but a mediocre response rate of 45% at 12 months after a single intra-articular injection with autologous MFAT. Assessment of bone marrow lesions on MRI can be helpful to increase the therapeutic responsiveness of MFAT up to 70% at 12 months. In comparison to repetitive injection therapies such as cortisone, hyaluronic acid, and PRP, administration of MFAT might become a relevant alternative in well-selected patients with symptomatic knee OA. Full article
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10 pages, 846 KiB  
Article
Identification of Patients with Similar Gait Compensating Strategies Due to Unilateral Hip Osteoarthritis and the Effect of Total Hip Replacement: A Secondary Analysis
by Stefan van Drongelen, Bernd J. Stetter, Harald Böhm, Felix Stief, Thorsten Stein and Andrea Meurer
J. Clin. Med. 2021, 10(10), 2167; https://doi.org/10.3390/jcm10102167 - 17 May 2021
Cited by 10 | Viewed by 2253
Abstract
Despite good clinical functional outcome, deficits in gait biomechanics exist 2 years after total hip replacement surgery. The aims of this research were (1) to group patients showing similar gait adaptations to hip osteoarthritis and (2) to investigate the effect of the surgical [...] Read more.
Despite good clinical functional outcome, deficits in gait biomechanics exist 2 years after total hip replacement surgery. The aims of this research were (1) to group patients showing similar gait adaptations to hip osteoarthritis and (2) to investigate the effect of the surgical treatment on gait kinematics and external joint moments. In a secondary analysis, gait data of 51 patients with unilateral hip osteoarthritis were analyzed. A k-means cluster analysis was performed on scores derived via a principal component analysis of the gait kinematics. Preoperative and postoperative datasets were statistically tested between clusters and 46 healthy controls. The first three principal components incorporated hip flexion/extension, pelvic tilt, foot progression angle and thorax tilt. Two clusters were discriminated best by the peak hip extension during terminal stance. Both clusters deviated from healthy controls in spatio-temporal, kinematic and kinetic parameters. The cluster with less hip extension deviated significantly more. The clusters improved postoperatively but differences to healthy controls were still present one year after surgery. A poor preoperative gait pattern in patients with unilateral hip osteoarthritis is associated with worse gait kinematics after total hip replacement. Further research should focus on the identification of patients who can benefit from an adapted or individualized rehabilitation program. Full article
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6 pages, 1104 KiB  
Article
Intra-Articular Administration of Autologous Purified Adipose Tissue Associated with Arthroscopy Ameliorates Knee Osteoarthritis Symptoms
by Marco Caforio and Carmelo Nobile
J. Clin. Med. 2021, 10(10), 2053; https://doi.org/10.3390/jcm10102053 - 11 May 2021
Cited by 8 | Viewed by 1583
Abstract
The aim of this study was to evaluate the safety and efficacy of the intra-articular administration of autologous purified adipose tissue to treat knee osteoarthritis (OA) following arthroscopy. Thirty patients with radiological evidence of knee OA were recruited. A small liposuction and arthroscopic [...] Read more.
The aim of this study was to evaluate the safety and efficacy of the intra-articular administration of autologous purified adipose tissue to treat knee osteoarthritis (OA) following arthroscopy. Thirty patients with radiological evidence of knee OA were recruited. A small liposuction and arthroscopic lavage and debridement were performed in the same surgical time. The harvested fat was processed intraoperatively with Lipocell (Tiss’You, RSM) to purify the adipose tissue injected into the knee. Clinical evaluations were performed with VAS, Womac, and Lequesne questionnaires before treatment and after 1, 3, 6, and 12 months of follow-up. Pain, measured with VAS, significantly decreased, showing a reduction of 53% after 1 month and 83% after a year. Functional recovery, measured with Womac, showed an improvement of 47% after 1 month post-treatment and 84% after 1 year. No adverse effects have been observed. The intra-articular administration of purified adipose tissue associated with arthroscopic lavage and debridement is a safe and significantly effective strategy in improving the symptoms of knee osteoarthritis in up to 1 year of follow-up. Full article
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12 pages, 1061 KiB  
Article
A Retrospective Analysis of Characteristic Features of Responders and Impaired Patients to a Single Injection of Pure Platelet-Rich Plasma in Knee Osteoarthritis
by Cécilia Bec, Axelle Rousset, Thibault Brandin, Pauline François, Sitraka Rabarimeriarijaona, Chloé Dumoulin, Gaëlle Heleu, Fanny Grimaud, Julie Veran, Guy Magalon, Françoise Dignat-George, Florence Sabatier, Marie-Laure Louis and Jérémy Magalon
J. Clin. Med. 2021, 10(8), 1748; https://doi.org/10.3390/jcm10081748 - 17 Apr 2021
Cited by 6 | Viewed by 2185
Abstract
(1) Background: The emergence of injectable “biologic” medication creates a new approach to treat osteoarthritis (OA). Among them, the use of intra-articular injection of PRP became widespread despite the absence of consensus regarding its optimal composition. The aim of this study was to [...] Read more.
(1) Background: The emergence of injectable “biologic” medication creates a new approach to treat osteoarthritis (OA). Among them, the use of intra-articular injection of PRP became widespread despite the absence of consensus regarding its optimal composition. The aim of this study was to retrospectively correlate an extensive biological characterization of injected PRP to the clinical responses of patients presenting knee OA. (2) Methods: This retrospective study included 75 patients with knee OA. Cartilage lesions were assessed using magnetic resonance imaging and the International Cartilage Regeneration Society (ICRS) classification. PRP extensive biological characterization was performed and patients’ subjective symptoms were recorded before injection and 3 and 6 months after injection using the Knee injury and Osteoarthritis Outcome Score (KOOS). Responders were defined by an improvement of 10 points on KOOS. (3) Results: At 6 months, 63.0% of the patients were responders. Impairment was characterized by a significantly higher proportion of patients with three compartments altered at baseline MRI and receiving a significantly higher dose of platelets compared to responders. (4) Conclusions: Single injection of pure PRP resulted in significant clinical improvement in the management of knee OA. Both baseline MRI and PRP biological features may be predictive factors of the clinical response, highlighting that a better understanding of action mechanism of PRP is still required. Full article
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9 pages, 483 KiB  
Article
Pilot Study to Evaluate the Efficacy of Polynucleotide Sodium Compared to Sodium Hyaluronate and Crosslinked Sodium Hyaluronate in Patients with Knee Osteoarthritis
by Ji Yeong Kim, Yoo Na Kim, Yu Jung Lee, Sung Eun Sim, Yu Ri Ko, Jin Woo Shim, Ku Sang Lee, Mina Joo and Hue Jung Park
J. Clin. Med. 2021, 10(5), 1138; https://doi.org/10.3390/jcm10051138 - 09 Mar 2021
Cited by 7 | Viewed by 3598
Abstract
Degenerative arthritis of the knee joint has become a major social problem worldwide due to population aging. There are several treatment options for knee osteoarthritis, and the intraarticular injection of sodium hyaluronate is commonly selected by many clinicians as a nonsurgical treatment. However, [...] Read more.
Degenerative arthritis of the knee joint has become a major social problem worldwide due to population aging. There are several treatment options for knee osteoarthritis, and the intraarticular injection of sodium hyaluronate is commonly selected by many clinicians as a nonsurgical treatment. However, the efficacy of the treatment is controversial. In this pilot study, we aimed to compare polynucleotide sodium (Conjuran®) with sodium hyaluronate (Hyruan Plus®) and 1,4-butanediol diglycidyl ether-crosslinked sodium hyaluronate (Synovian®) in terms of analgesic efficacy after intraarticular injection in patients with knee osteoarthritis. One of the three intraarticular agents was selected according to what agents were available for outpatients when each patient was enrolled in the study. The 15 enrolled patients were subdivided into 3 groups of 5 patients each. Three injections were performed under ultrasound guidance at a 1-week intervals over a total of 3 weeks. The visual analog scale (VAS) score, the Korean version of the Western Ontario and McMaster Universities Arthritis Index (K-WOMAC), the EuroQol five-dimension scale (EQ-5D) score, and the Korean version of the painDETECT Questionnaire (K-PDQ) score were evaluated before injection and at 1, 2, and 6 weeks after the start of the treatment protocol. The primary endpoint was the change in weight-bearing pain at 4 weeks after the last injection. Secondary endpoints included pain at rest and during walking and the K-WOMAC, EQ-5D, and K-PDQ scores. Weight-bearing pain decreased significantly more from pretreatment to 6 weeks after the start of the treatment protocol in the polynucleotide sodium-treated patients than in the patients who were treated with other agents (p = 0.006, one-way ANOVA). There were no significant between-group differences in the other secondary endpoints. No adverse events occurred. In conclusion, polynucleotide sodium could effectively reduce weight-bearing pain in the patients with knee osteoarthritis compared to standard hyaluronic acid viscosupplementation. Full article
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10 pages, 1626 KiB  
Article
Cross-Sectional Association between Hypercholesterolemia and Knee Pain in the Elderly with Radiographic Knee Osteoarthritis: Data from the Korean National Health and Nutritional Examination Survey
by Byung Woo Cho, Du Seong Kim, Hyuck Min Kwon, Ick Hwan Yang, Woo-Suk Lee and Kwan Kyu Park
J. Clin. Med. 2021, 10(5), 933; https://doi.org/10.3390/jcm10050933 - 01 Mar 2021
Cited by 7 | Viewed by 2093
Abstract
Few studies have reported the relationship between knee pain and hypercholesterolemia in the elderly population with osteoarthritis (OA), independent of other variables. The aim of this study was to reveal the association between knee pain and metabolic diseases including hypercholesterolemia using a large-scale [...] Read more.
Few studies have reported the relationship between knee pain and hypercholesterolemia in the elderly population with osteoarthritis (OA), independent of other variables. The aim of this study was to reveal the association between knee pain and metabolic diseases including hypercholesterolemia using a large-scale cohort. A cross-sectional study was conducted using data from the Korea National Health and the Nutrition Examination Survey (KNHANES-V, VI-1; 2010–2013). Among the subjects aged ≥60 years, 7438 subjects (weighted number estimate = 35,524,307) who replied knee pain item and performed the simple radiographs of knee were enrolled. Using multivariable ordinal logistic regression analysis, variables affecting knee pain were identified, and the odds ratio (OR) was calculated. Of the 35,524,307 subjects, 10,630,836 (29.9%) subjects experienced knee pain. Overall, 20,290,421 subjects (56.3%) had radiographic OA, and 8,119,372 (40.0%) of them complained of knee pain. Multivariable ordinal logistic regression analysis showed that among the metabolic diseases, only hypercholesterolemia was positively correlated with knee pain in the OA group (OR 1.24; 95% Confidence Interval 1.02–1.52, p = 0.033). There were no metabolic diseases correlated with knee pain in the non-OA group. This large-scale study revealed that in the elderly, hypercholesterolemia was positively associated with knee pain independent of body mass index and other metabolic diseases in the OA group, but not in the non-OA group. These results will help in understanding the nature of arthritic pain, and may support the need for exploring the longitudinal associations. Full article
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14 pages, 1813 KiB  
Article
Changes in Cartilage Thickness and Denuded Bone Area after Knee Joint Distraction and High Tibial Osteotomy—Post-Hoc Analyses of Two Randomized Controlled Trials
by Mylène P. Jansen, Susanne Maschek, Ronald J. van Heerwaarden, Simon C. Mastbergen, Wolfgang Wirth, Floris P. J. G. Lafeber and Felix Eckstein
J. Clin. Med. 2021, 10(2), 368; https://doi.org/10.3390/jcm10020368 - 19 Jan 2021
Cited by 14 | Viewed by 2398
Abstract
High tibial osteotomy (HTO) and knee joint distraction (KJD) are joint-preserving treatments that unload the more affected compartment (MAC) in knee osteoarthritis. This post-hoc study compares two-year cartilage-thickness changes after treatment with KJD vs. HTO, and identifies factors predicting cartilage restoration. Patients indicated [...] Read more.
High tibial osteotomy (HTO) and knee joint distraction (KJD) are joint-preserving treatments that unload the more affected compartment (MAC) in knee osteoarthritis. This post-hoc study compares two-year cartilage-thickness changes after treatment with KJD vs. HTO, and identifies factors predicting cartilage restoration. Patients indicated for HTO were randomized to KJD (KJDHTO) or HTO treatment. Patients indicated for total knee arthroplasty received KJD (KJDTKA). Outcomes were the MRI mean MAC cartilage thickness and percentage of denuded bone area (dABp) change two years after treatment, using radiographic joint space width (JSW) as the reference. Cohen’s d was used for between-group effect sizes. Post-treatment, KJDHTO patients (n = 18) did not show significant changes. HTO patients (n = 33) displayed a decrease in MAC cartilage thickness and an increase in dABp, but an increase in JSW. KJDTKA (n = 18) showed an increase in MAC cartilage thickness and JSW, and a decrease in dABp. Osteoarthritis severity was the strongest predictor of cartilage restoration. Kellgren–Lawrence grade ≥3 showed significant restoration (p < 0.01) after KJD; grade ≤2 did not. Effect sizes between severe KJD and HTO patients were large for MAC MRI cartilage thickness (d = 1.09; p = 0.005) and dABp (d = 1.13; p = 0.003), but not radiographic JSW (d = 0.28; p = 0.521). This suggests that in knee osteoarthritis patients with high disease severity, KJD may be more efficient in restoring cartilage thickness. Full article
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11 pages, 1931 KiB  
Article
Cartilage Micrografts as a Novel Non-Invasive and Non-Arthroscopic Autograft Procedure for Knee Chondropathy: Three-Year Follow-Up Study
by Marco Marcarelli, Marcello Zappia, Lorenzo Rissolio, Chiara Baroni, Carlo Astarita, Letizia Trovato and Antonio Graziano
J. Clin. Med. 2021, 10(2), 322; https://doi.org/10.3390/jcm10020322 - 17 Jan 2021
Cited by 8 | Viewed by 3254
Abstract
(1) Background: Focal chondral defects of the knee can significantly impair patient quality of life. Although different options are available, they are still not conclusive and have several limitations. The aim of this study was to evaluate the role of autologous cartilage micrografts [...] Read more.
(1) Background: Focal chondral defects of the knee can significantly impair patient quality of life. Although different options are available, they are still not conclusive and have several limitations. The aim of this study was to evaluate the role of autologous cartilage micrografts in the treatment of knee chondropathy. (2) Methods: Eight patients affected by knee chondropathy were evaluated before and after 6 months and 3 years following autologous cartilage micrografts by magnetic resonance imaging (MRI) for cartilage measurement and clinical assessment. (3) Results: All patients recovered daily activities, reporting pain reduction without the need for analgesic therapy; Oxford Knee Score (OKS) was 28.4 ± 6 and 40.8 ± 6.2 and visual analogue scale (VAS) was 5.5 ± 1.6 and 1.8 ± 0.7 before and after 6 months following treatment, respectively. Both scores remained stable after 3 years. Lastly, a significant improvement of the cartilage thickness was observed using MRI after 3 years. (4) Conclusions: Autologous cartilage micrografts can promote the formation of new cartilage, and could be a valid approach for the treatment of knee chondropathy. Full article
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Review

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13 pages, 768 KiB  
Review
Exosomes Derived from Non-Classic Sources for Treatment of Post-Traumatic Osteoarthritis and Cartilage Injury of the Knee: In Vivo Review
by Dan Li, Puneet Gupta, Nicholas A. Sgaglione and Daniel A. Grande
J. Clin. Med. 2021, 10(9), 2001; https://doi.org/10.3390/jcm10092001 - 07 May 2021
Cited by 9 | Viewed by 2772
Abstract
Osteoarthritis of the knee is one of the most common chronic, debilitating musculoskeletal conditions. Current conservative treatment modalities such as weight loss, non-steroidal anti-inflammatory drugs, and intra-articular steroid injections often only provide temporary pain relief and are unsatisfactory for long-term management. Though end [...] Read more.
Osteoarthritis of the knee is one of the most common chronic, debilitating musculoskeletal conditions. Current conservative treatment modalities such as weight loss, non-steroidal anti-inflammatory drugs, and intra-articular steroid injections often only provide temporary pain relief and are unsatisfactory for long-term management. Though end stage osteoarthritis of the knee can be managed with total knee arthroplasty (TKA), finding alternative non-surgical options to delay or prevent the need for TKA are needed due to the increased healthcare costs and expenditures associated with TKA. Exosomes have been of particular interest given recent findings highlighting that stem cells may at least partially mediate some of their effects through the release of extracellular vesicles, such as exosomes. As such, better understanding the biological mechanisms and potential therapeutic effects of these exosomes is necessary. Here, we review in vivo studies that highlight the potential clinical use of exosomes derived from non-classical sources (not bone marrow or adipose derived MSCs derived MSCs) for osteoarthritis of the knee. Full article
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22 pages, 1401 KiB  
Review
Osteoarthritis: Novel Molecular Mechanisms Increase Our Understanding of the Disease Pathology
by Susanne Grässel, Frank Zaucke and Henning Madry
J. Clin. Med. 2021, 10(9), 1938; https://doi.org/10.3390/jcm10091938 - 30 Apr 2021
Cited by 42 | Viewed by 4675
Abstract
Although osteoarthritis (OA) is the most common musculoskeletal condition that causes significant health and social problems worldwide, its exact etiology is still unclear. With an aging and increasingly obese population, OA is becoming even more prevalent than in previous decades. Up to 35% [...] Read more.
Although osteoarthritis (OA) is the most common musculoskeletal condition that causes significant health and social problems worldwide, its exact etiology is still unclear. With an aging and increasingly obese population, OA is becoming even more prevalent than in previous decades. Up to 35% of the world’s population over 60 years of age suffers from symptomatic (painful, disabling) OA. The disease poses a tremendous economic burden on the health-care system and society for diagnosis, treatment, sick leave, rehabilitation, and early retirement. Most patients also experience sleep disturbances, reduced capability for exercising, lifting, and walking and are less capable of working, and maintaining an independent lifestyle. For patients, the major problem is disability, resulting from joint tissue destruction and pain. So far, there is no therapy available that effectively arrests structural deterioration of cartilage and bone or is able to successfully reverse any of the existing structural defects. Here, we elucidate novel concepts and hypotheses regarding disease progression and pathology, which are relevant for understanding underlying the molecular mechanisms as a prerequisite for future therapeutic approaches. Emphasis is placed on topographical modeling of the disease, the role of proteases and cytokines in OA, and the impact of the peripheral nervous system and its neuropeptides. Full article
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23 pages, 431 KiB  
Review
A Roadmap of In Vitro Models in Osteoarthritis: A Focus on Their Biological Relevance in Regenerative Medicine
by Isabella Bartolotti, Livia Roseti, Mauro Petretta, Brunella Grigolo and Giovanna Desando
J. Clin. Med. 2021, 10(9), 1920; https://doi.org/10.3390/jcm10091920 - 28 Apr 2021
Cited by 19 | Viewed by 3867
Abstract
Osteoarthritis (OA) is a multifaceted musculoskeletal disorder, with a high prevalence worldwide. Articular cartilage and synovial membrane are among the main biological targets in the OA microenvironment. Gaining more knowledge on the accuracy of preclinical in vitro OA models could open innovative avenues [...] Read more.
Osteoarthritis (OA) is a multifaceted musculoskeletal disorder, with a high prevalence worldwide. Articular cartilage and synovial membrane are among the main biological targets in the OA microenvironment. Gaining more knowledge on the accuracy of preclinical in vitro OA models could open innovative avenues in regenerative medicine to bridge major gaps, especially in translation from animals to humans. Our methodological approach entailed searches on Scopus, the Web of Science Core Collection, and EMBASE databases to select the most relevant preclinical in vitro models for studying OA. Predicting the biological response of regenerative strategies requires developing relevant preclinical models able to mimic the OA milieu influencing tissue responses and organ complexity. In this light, standard 2D culture models lack critical properties beyond cell biology, while animal models suffer from several limitations due to species differences. In the literature, most of the in vitro models only recapitulate a tissue compartment, by providing fragmented results. Biotechnological advances may enable scientists to generate new in vitro models that combine easy manipulation and organ complexity. Here, we review the state-of-the-art of preclinical in vitro models in OA and outline how the different preclinical systems (inflammatory/biomechanical/microfluidic models) may be valid tools in regenerative medicine, describing their pros and cons. We then discuss the prospects of specific and combinatorial models to predict biological responses following regenerative approaches focusing on mesenchymal stromal cells (MSCs)-based therapies to reduce animal testing. Full article
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