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Osteoarthritis and Cartilage Regeneration: From Pathophysiology to Novel Therapeutic Approaches

A special issue of Applied Sciences (ISSN 2076-3417). This special issue belongs to the section "Applied Biosciences and Bioengineering".

Deadline for manuscript submissions: closed (15 December 2021) | Viewed by 40658

Special Issue Editors


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Guest Editor
Laboratory of Experimental Surgery and Regenerative Medicine (ExperiMed), Clinic for General, Trauma and Reconstructive Surgery, Ludwig-Maximilians-University, Munich, Germany
Interests: cartilage; skeletal development; osteoarthritis; integrins; cartilage regeneration; chondrogenic differentiation; cartilaginous extracellular matrix.

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Co-Guest Editor
CNRS UMR 5305 Laboratory of Tissue Biology and Therapeutic Engineering, Université Claude Bernard Lyon1, Univ Lyon, 69367 Lyon, France
Interests: cartilage tissue

Special Issue Information

Dear Colleagues,

Osteoarthritis (OA) is one of the most common musculoskeletal conditions, causing significant disability and morbidity across the population. OA is a degenerative disorder of the synovial joints viewed as a single organ, eventually culminating in the irreversible degradation of the articular cartilage. Despite the widespread awareness of the disease, the pathogenesis of OA is not completely understood and, to date, no disease-modifying osteoarthritis treatments have been developed successfully. Furthermore, articular cartilage has a poor intrinsic healing capacity and the regeneration of degenerated cartilage remains a clinical challenge. 

This Special Issue is intended to deepen our current understanding of the pathophysiological mechanisms involved in OA and look forward to novel therapeutic strategies and research directions for treating OA and restoring degenerated cartilage.

We encourage researchers to contribute to this Special Issue with original research papers that investigate the multifaceted pathophysiology of OA using cellular, molecular, genetic, and functional approaches. Novel cell-based, extracellular vesicle, pharmacological, and gene therapy studies, including trials evaluating potential OA candidates using preclinical animal models, are highly recommended. We would also welcome comprehensive reviews summarizing our current knowledge of osteoarthritis and cartilage regeneration and fostering the link between achievements in basic science and clinical outcomes.

Dr. Paolo Alberton
Guest Editor
Dr. Emeline Perrier-Groult
Co-Guest Editor

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Keywords

  • pathogenesis of osteoarthritis (OA)
  • cartilage regeneration
  • OA mouse models
  • pharmacological, cell-based, and gene therapy strategies
  • inflammation in OA
  • tissue engineering
  • OA biomarkers

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Published Papers (14 papers)

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Research

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15 pages, 3718 KiB  
Article
Nano-Scale Mechanical Properties of the Articular Cartilage Zones in a Mouse Model of Post-Traumatic Osteoarthritis
by Lutz Fleischhauer, Dominique Muschter, Zsuzsanna Farkas, Susanne Grässel, Attila Aszodi, Hauke Clausen-Schaumann and Paolo Alberton
Appl. Sci. 2022, 12(5), 2596; https://doi.org/10.3390/app12052596 - 2 Mar 2022
Cited by 4 | Viewed by 2369
Abstract
Destabilization of the medial meniscus (DMM) surgery in mice is used to elucidate the mechanism of post-traumatic osteoarthritis (PT-OA). The study of cartilage biomechanics in PT-OA is important for understanding the pathophysiology of the condition. We used indentation-type atomic force microscopy (IT-AFM) to [...] Read more.
Destabilization of the medial meniscus (DMM) surgery in mice is used to elucidate the mechanism of post-traumatic osteoarthritis (PT-OA). The study of cartilage biomechanics in PT-OA is important for understanding the pathophysiology of the condition. We used indentation-type atomic force microscopy (IT-AFM) to assess the nanostiffness of the interterritorial matrix of articular cartilage (AC) zones in the medial and the lateral tibia plateau (MTP and LTP) on native tissue sections 2 and 8 weeks after DMM or Sham surgery. At 2 weeks, pronounced stiffening of the DMM AC was observed compared to Sham, with the most marked changes occurring in the superficial zone and affecting the proteoglycan moiety rather than the collagen network. The LTP cartilage was obviously stiffer than the MTP in DMM, but not in Sham. At 8 weeks, only modest differences in nanostiffness were observed between DMM and Sham. The difference in stiffness between MTP and LTP was reduced, and the proteoglycan and collagen phases changed in a more similar manner. Interestingly, the deep zone was softer in the DMM compared to the Sham. Sham AC showed an increase in stiffness between 2 and 8 weeks, a trend that was counteracted in the DMM group. Collectively, our study demonstrates that nano-scale IT-AFM is a sensitive tool to monitor biomechanical changes during the course of PT-OA. Full article
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19 pages, 4456 KiB  
Article
Mesenchymal Stromal Cells (MSCs) Isolated from Various Tissues of the Human Arthritic Knee Joint Possess Similar Multipotent Differentiation Potential
by Mike Wagenbrenner, Konrad Poker, Tizian Heinz, Marietta Herrmann, Konstantin Horas, Regina Ebert, Susanne Mayer-Wagner, Boris M. Holzapfel, Maximilian Rudert, Andre F. Steinert and Manuel Weißenberger
Appl. Sci. 2022, 12(4), 2239; https://doi.org/10.3390/app12042239 - 21 Feb 2022
Viewed by 1861
Abstract
(1) Background: The mesenchymal stromal cells (MSCs) of different tissue origins are applied in cell-based chondrogenic regeneration. However, there is a lack of comparability determining the most suitable cell source for the tissue engineering (TE) of cartilage. The purpose of this study was [...] Read more.
(1) Background: The mesenchymal stromal cells (MSCs) of different tissue origins are applied in cell-based chondrogenic regeneration. However, there is a lack of comparability determining the most suitable cell source for the tissue engineering (TE) of cartilage. The purpose of this study was to compare the in vitro chondrogenic potential of MSC-like cells from different tissue sources (bone marrow, meniscus, anterior cruciate ligament, synovial membrane, and the infrapatellar fat pad removed during total knee arthroplasty (TKA)) and define which cell source is best suited for cartilage regeneration. (2) Methods: MSC-like cells were isolated from five donors and expanded using adherent monolayer cultures. Differentiation was induced by culture media containing specific growth factors. Transforming growth factor (TGF)-ß1 was used as the growth factor for chondrogenic differentiation. Osteogenesis and adipogenesis were induced in monolayer cultures for 27 days, while pellet cell cultures were used for chondrogenesis for 21 days. Control cultures were maintained under the same conditions. After, the differentiation period samples were analyzed, using histological and immunohistochemical staining, as well as molecularbiological analysis by RT-PCR, to assess the expression of specific marker genes. (3) Results: Plastic-adherent growth and in vitro trilineage differentiation capacity of all isolated cells were proven. Flow cytometry revealed the clear co-expression of surface markers CD44, CD73, CD90, and CD105 on all isolated cells. Adipogenesis was validated through the formation of lipid droplets, while osteogenesis was proven by the formation of calcium deposits within differentiated cell cultures. The formation of proteoglycans was observed during chondrogenesis in pellet cultures, with immunohistochemical staining revealing an increased relative gene expression of collagen type II. RT-PCR proved an elevated expression of specific marker genes after successful differentiation, with no significant differences regarding different cell source of native tissue. (4) Conclusions: Irrespective of the cell source of native tissue, all MSC-like cells showed multipotent differentiation potential in vitro. The multipotent differentiation capacity did not differ significantly, and chondrogenic differentiation was proven in all pellet cultures. Therefore, cell suitability for cell-based cartilage therapies and tissue engineering is given for various tissue origins that are routinely removed during total knee arthroplasty (TKA). This study might provide essential information for the clinical tool of cell harvesting, leading to more flexibility in cell availability. Full article
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15 pages, 4667 KiB  
Article
Design and 3D Printing of Interbody Fusion Cage Based on TPMS Porous Structure
by Jinlai Qi, Youping Gong, Honghao Chen, Junling He, Zizhou Qiao, Yi Chen, Huifeng Shao, Wenxin Li, Guojin Chen, Maofa Wang, Chuanping Zhou and Xiang Zhang
Appl. Sci. 2021, 11(23), 11149; https://doi.org/10.3390/app112311149 - 24 Nov 2021
Cited by 5 | Viewed by 2759
Abstract
To solve the mismatch between the comprehensive mechanical properties of the spinal fusion cage and body, a fusion cage inner hole design method based on controllable TPMS-P to characterize the inner hole structure is proposed to solve the related problems. Firstly, the method [...] Read more.
To solve the mismatch between the comprehensive mechanical properties of the spinal fusion cage and body, a fusion cage inner hole design method based on controllable TPMS-P to characterize the inner hole structure is proposed to solve the related problems. Firstly, the method of TPMS-P parameterization was used to construct the bionic porous structure model, which was designed as the linear gradual internal porous structure model. Then, we optimized the topology of the obtained porous structure implants to achieve precise control of the overall comprehensive mechanical properties of the fusion cage structure and obtain an optimized model that matched the mechanical properties of the fusion cage. To verify whether the method met the requirements, its simulation model was established. The porous structure was fabricated by selective laser processing, and its properties were tested and analyzed. The results show that its yield strength is 79.83 MPa, which match well with spinal bone tissue. Full article
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16 pages, 2281 KiB  
Article
Protective Effects of Annatto Tocotrienol and Palm Tocotrienol-Rich Fraction on Chondrocytes Exposed to Monosodium Iodoacetate
by Kok-Lun Pang, Norzana Abd Ghafar, Ima Nirwana Soelaiman and Kok-Yong Chin
Appl. Sci. 2021, 11(20), 9643; https://doi.org/10.3390/app11209643 - 15 Oct 2021
Cited by 10 | Viewed by 1924
Abstract
Background: This study aimed to compare the chondroprotective efficacy and mechanism of annatto tocotrienol (AnTT) and palm tocotrienol-rich fraction (PT3) using SW1353 chondrocytes treated with monosodium iodoacetate (MIA). Methods: The chondrocytes were incubated with AnTT or PT3 in advance or concurrently with MIA [...] Read more.
Background: This study aimed to compare the chondroprotective efficacy and mechanism of annatto tocotrienol (AnTT) and palm tocotrienol-rich fraction (PT3) using SW1353 chondrocytes treated with monosodium iodoacetate (MIA). Methods: The chondrocytes were incubated with AnTT or PT3 in advance or concurrently with MIA for 24 h. The viability of the cells was tested with an MTT assay. The 8-isoprostane F2-α, extracellular matrix proteins, metalloproteinase and sex-determining region Y box protein 9 (SOX9) levels were determined using immunoassays. Results: AnTT and PT3 reversed an MIA-induced decrease in chondrocyte viability when incubated together with MIA (p < 0.05). Prior incubation with both mixtures did not produce the same effects. AnTT and PT3 cotreatment could suppress 8-isoprostane F2-α level in chondrocytes exposed to MIA (p < 0.01). Co-exposure to tocotrienols and MIA increased the type II collagen/type I collagen ratio in chondrocytes (p < 0.01). In addition, the co-exposure of AnTT and MIA for 24 h significantly upregulated SOX9, type II collagen and aggrecan levels (p < 0.05), which was not observed with co-exposure of PT3 and MIA, AnTT or PT3 exposure alone. Conclusion: AnTT and PT3 could prevent a reduction in chondrocyte viability following MIA exposure by reducing oxidative stress. In addition, AnTT might induce self-repair and anabolic activities in chondrocytes challenged with MIA. Full article
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15 pages, 4029 KiB  
Article
Direct Perfusion Improves Redifferentiation of Human Chondrocytes in Fibrin Hydrogel with the Deposition of Cartilage Pericellular Matrix
by Alexandre Dufour, Frédéric Mallein-Gerin and Emeline Perrier-Groult
Appl. Sci. 2021, 11(19), 8923; https://doi.org/10.3390/app11198923 - 24 Sep 2021
Cited by 5 | Viewed by 2619
Abstract
Articular cartilage has limited potential for self-repair, and cell-based strategies combining scaffolds and chondrocytes are currently used to treat cartilage injuries. However, achieving a satisfying level of cell redifferentiation following expansion remains challenging. Hydrogels and perfusion bioreactors are known to exert beneficial cues [...] Read more.
Articular cartilage has limited potential for self-repair, and cell-based strategies combining scaffolds and chondrocytes are currently used to treat cartilage injuries. However, achieving a satisfying level of cell redifferentiation following expansion remains challenging. Hydrogels and perfusion bioreactors are known to exert beneficial cues on chondrocytes; however, the effect of a combined approach on the quality of cartilage matrix deposited by cells is not fully understood. Here, we combined soluble factors (BMP-2, Insulin, and Triiodothyronine, that is, BIT), fibrin hydrogel, direct perfusion and human articular chondrocytes (HACs) to engineer large cartilage tissues. Following cell expansion, cells were embedded in fibrin gels and cultivated under either static or perfusion conditions. The nature of the matrix synthesized was assessed by Western blotting and immunohistochemistry. The stability of cartilage grafts and integration with native tissue were also investigated by subcutaneous implantation of human osteochondral cylinders in nude mice. Perfusion preconditioning improved matrix quality and spatial distribution. Specifically, perfusion preconditioning resulted in a matrix rich in type II collagen but not in type I collagen, indicating the reconstruction of hyaline cartilage. Remarkably, the production of type VI collagen, the main component of the pericellular matrix, was also increased, indicating that chondrocytes were connecting to the hyaline matrix they produced. Full article
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10 pages, 2855 KiB  
Article
The Conformity of Rehabilitation Protocols Used for Different Cartilage Repairs of the Knee Joint—A Review on Rehabilitation Standards in German Speaking Countries
by Clemens Memmel, Werner Krutsch, Matthias Koch, Moritz Riedl, Leopold Henssler, Florian Zeman, Christian Knorr, Volker Alt and Christian Pfeifer
Appl. Sci. 2021, 11(19), 8873; https://doi.org/10.3390/app11198873 - 24 Sep 2021
Cited by 4 | Viewed by 2480
Abstract
The present study analysed current rehabilitation protocols to investigate whether there is a standard for early rehabilitation after microfracturing (MFX), matrix-assisted cartilage transplantation (MACT), and osteochondral autograft transfer (OATS) of the knee joint in clinical routine, and if rehabilitation protocols differ in the [...] Read more.
The present study analysed current rehabilitation protocols to investigate whether there is a standard for early rehabilitation after microfracturing (MFX), matrix-assisted cartilage transplantation (MACT), and osteochondral autograft transfer (OATS) of the knee joint in clinical routine, and if rehabilitation protocols differ in the repair technique used or the localization of the cartilage defect. The evaluation included rehabilitation criteria such as weight-bearing, range of motion, use of an orthosis, motion therapy, and rehabilitation training during the early rehabilitation phase after MFX, MACT, and OATS of the femorotibial and retropatellar joint space. We analysed 153 rehabilitation protocols after cartilage repair of the knee joint, including 137 protocols for after repair of the main weight-bearing (femorotibial) area and 16 for after retropatellar cartilage repair. Most of the protocols differed significantly according to the location of the repair and the procedure performed. Our findings indicate that full weight-bearing can be achieved significantly faster after MFX (5.6 weeks) and OATS (5.3 weeks) than after MACT of the main weight-bearing zone (6.6 weeks, p < 0.001). In addition, after retropatellar cartilage repair, patients are allowed full weight-bearing after 2.1 weeks compared to the main weight-bearing zone (5.3–6.6 weeks; p < 0.001). No standardized rehabilitation recommendations have been established. The present study shows that rehabilitation needs to be adjusted to the surgical technique and the location of the defect zone, and further investigation is warranted to establish standardized rehabilitation protocols after cartilage repair of the knee joint. Full article
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13 pages, 2724 KiB  
Article
Effects of Palm Tocotrienol-Rich Fraction Alone or in Combination with Glucosamine Sulphate on Grip Strength, Cartilage Structure and Joint Remodelling Markers in a Rat Model of Osteoarthritis
by Hiba Murtadha Al-Saadi, Kok-Yong Chin, Fairus Ahmad, Elvy Suhana Mohd Ramli, Azlan Mohd Arlamsyah, Fadhlullah Zuhair Japar Sidik, Juliana Abdul Hamid and Ima Nirwana Soelaiman
Appl. Sci. 2021, 11(18), 8577; https://doi.org/10.3390/app11188577 - 15 Sep 2021
Cited by 11 | Viewed by 2419
Abstract
Background: Osteoarthritis is a degenerative joint disease lacking disease-modifying therapeutic agents. This study aimed to compare the effects of palm tocotrienol-rich fraction (TRF), glucosamine sulphate, and both agents combined in rats with osteoarthritis induced by monosodium iodoacetate (MIA). Methods: Thirty adult male rats [...] Read more.
Background: Osteoarthritis is a degenerative joint disease lacking disease-modifying therapeutic agents. This study aimed to compare the effects of palm tocotrienol-rich fraction (TRF), glucosamine sulphate, and both agents combined in rats with osteoarthritis induced by monosodium iodoacetate (MIA). Methods: Thirty adult male rats were randomized into normal control, and osteoarthritis groups were treated orally daily with vehicle, palm TRF (100 mg/kg), glucosamine sulphate (250 mg/kg), and both agents combined for 4 weeks. Body weight and grip strength were measured weekly. After being sacrificed, the joints and blood were harvested for histology and serum cartilage oligomeric matrix protein (COMP) levels. Results: The body weight of the rats receiving treatment rebounded significantly after an initial reduction (vs osteoarthritic control, p < 0.05). The rats receiving combined treatments showed significantly better grip strength than the osteoarthritic control and individual treatment groups (p < 0.05). The serum COMP level was lower in all the treated groups (vs osteoarthritic control, p < 0.05). Cartilage histology of the treated rats was not significantly improved (vs osteoarthritic control, p > 0.05). Conclusion: The combination of palm TRF and glucosamine sulphate was more effective than individual agents in improving the grip strength of the rats, but the cartilage damage might need more time to heal. Full article
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16 pages, 1664 KiB  
Article
Intermittent Dynamic Compression Confers Anabolic Effects in Articular Cartilage
by Amalie Engstrøm, Frederik S. Gillesberg, Solveig S. Groen, Peder Frederiksen, Anne-Christine Bay-Jensen, Morten A. Karsdal and Christian S. Thudium
Appl. Sci. 2021, 11(16), 7469; https://doi.org/10.3390/app11167469 - 14 Aug 2021
Cited by 3 | Viewed by 2684
Abstract
(1) Background: Mechanical loading is an essential part of the function and maintenance of the joint. Despite the importance of intermittent mechanical loading, this factor is rarely considered in preclinical models of cartilage, limiting their translatability. The aim of this study was to [...] Read more.
(1) Background: Mechanical loading is an essential part of the function and maintenance of the joint. Despite the importance of intermittent mechanical loading, this factor is rarely considered in preclinical models of cartilage, limiting their translatability. The aim of this study was to investigate the effects of intermittent dynamic compression on the extracellular matrix during long-term culture of bovine cartilage explants. (2) Methods: Bovine articular cartilage explants were cultured for 21 days and subjected to 20 min of 1 Hz cyclic compressive loading five consecutive days each week. Cartilage remodeling was investigated in the presence of IGF-1 or TGF-β1, as well as a TGF-β receptor 1 (ALK5) kinase inhibitor and assessed with biomarkers for type II collagen formation (PRO-C2) and fibronectin degradation (FBN-C). (3) Results: Compression of cartilage explants increased the release of PRO-C2 and FBN-C to the conditioned media and, furthermore, IGF-1 and compression synergistically increased PRO-C2 release. Inhibition of ALK5 blocked PRO-C2 and FBN-C release in dynamically compressed explants. (4) Conclusions: Dynamic compression of cartilage explants increases both type II collagen formation and fibronectin degradation, and IGF-1 interacts synergistically with compression, increasing the overall impact on cartilage formation. These data show that mechanical loading is important to consider in translational cartilage models. Full article
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13 pages, 1669 KiB  
Article
Cartilage Repair Activity during Joint-Preserving Treatment May Be Accompanied by Osteophyte Formation
by Mylène P. Jansen, Simon C. Mastbergen, Fiona E. Watt, Elske J. Willemse, Tonia L. Vincent, Sander Spruijt, Pieter J. Emans, Roel J. H. Custers, Ronald J. van Heerwaarden and Floris P. J. G. Lafeber
Appl. Sci. 2021, 11(15), 7156; https://doi.org/10.3390/app11157156 - 3 Aug 2021
Cited by 2 | Viewed by 2974
Abstract
Knee joint distraction (KJD) treatment has shown cartilage repair and clinical improvement in patients with osteoarthritis, as has high tibial osteotomy (HTO). Following KJD, TGFβ-1 and IL-6 were increased in synovial fluid (SF), factors related to cartilage regeneration, but also to osteophyte formation. [...] Read more.
Knee joint distraction (KJD) treatment has shown cartilage repair and clinical improvement in patients with osteoarthritis, as has high tibial osteotomy (HTO). Following KJD, TGFβ-1 and IL-6 were increased in synovial fluid (SF), factors related to cartilage regeneration, but also to osteophyte formation. As such, osteophyte formation after both joint-preserving treatments was studied. Radiographic osteophyte size was measured before, one year, and two years after treatment. Changes were compared with natural progression in patients from the CHECK cohort before undergoing total knee arthroplasty. An additional KJD cohort underwent SF aspiration, and one-year Altman osteophyte score changes were compared to SF-marker changes during treatment. After two years, both KJD (n = 58) and HTO (n = 38) patients showed an increase in osteophyte size (+6.2 mm2 and +7.0 mm2 resp.; both p < 0.004), with no significant differences between treatments (p = 0.592). Untreated CHECK patients (n = 44) did not show significant two-year changes (+2.1 mm2; p = 0.207) and showed significant differences with KJD and HTO (both p < 0.044). In SF aspiration patients (n = 17), there were significant differences in TGFβ-1 changes (p = 0.044), but not IL-6 (p = 0.898), between patients with a decrease, no change, or increase in osteophyte Altman score. Since KJD and HTO showed joint space widening and clinical improvement accompanied by osteophyte formation, increased osteophytosis after joint-preserving treatments may be a bystander effect of cartilage repair activity related to intra-articular factors like TGFβ-1 and raises questions regarding osteophyte formation as solely characteristic of the joint degenerative process. Full article
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13 pages, 4964 KiB  
Article
Genetic Deletion of Interleukin-15 Is Not Associated with Major Structural Changes Following Experimental Post-Traumatic Knee Osteoarthritis in Rats
by Ermina Hadzic, Garth Blackler, Holly Dupuis, Stephen James Renaud, Christopher Thomas Appleton and Frank Beier
Appl. Sci. 2021, 11(15), 7118; https://doi.org/10.3390/app11157118 - 31 Jul 2021
Viewed by 1695
Abstract
Post-traumatic osteoarthritis (PTOA) is a degenerative joint disease, leading to articular cartilage breakdown, osteophyte formation, and synovitis, caused by an initial joint trauma. Pro-inflammatory cytokines increase catabolic activity and may perpetuate inflammation following joint trauma. Interleukin-15 (IL-15), a pro-inflammatory cytokine, is increased in [...] Read more.
Post-traumatic osteoarthritis (PTOA) is a degenerative joint disease, leading to articular cartilage breakdown, osteophyte formation, and synovitis, caused by an initial joint trauma. Pro-inflammatory cytokines increase catabolic activity and may perpetuate inflammation following joint trauma. Interleukin-15 (IL-15), a pro-inflammatory cytokine, is increased in OA patients, although its roles in PTOA pathophysiology are not well characterized. Here, we utilized Il15 deficient rats to examine the role of IL-15 in PTOA pathogenesis in an injury-induced model. OA was surgically induced in Il15 deficient Holtzman Sprague-Dawley rats and control wild-type rats to compare PTOA progression. Semi-quantitative scoring of the articular cartilage, subchondral bone, osteophyte size, and synovium was performed by two blinded observers. There was no significant difference between Il15 deficient rats and wild-type rats following PTOA-induction across articular cartilage damage, subchondral bone damage, and osteophyte scoring. Similarly, synovitis scoring across six parameters found no significant difference between genetic variants. Overall, IL-15 does not appear to play a key role in the development of structural changes in this surgically-induced rat model of PTOA. Full article
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16 pages, 4193 KiB  
Article
Knee MRI Underestimates the Grade of Cartilage Lesions
by Przemysław Krakowski, Robert Karpiński, Mariusz Jojczuk, Agata Nogalska and Józef Jonak
Appl. Sci. 2021, 11(4), 1552; https://doi.org/10.3390/app11041552 - 9 Feb 2021
Cited by 32 | Viewed by 6694
Abstract
Purpose: This study was conducted in order to evaluate the clinical utility of MRI in detecting cartilage lesions and its dependence on anatomical location and lesion grade. Methods: A retrospective analysis of MRI reports and arthroscopic findings was performed on 190 consecutive patients [...] Read more.
Purpose: This study was conducted in order to evaluate the clinical utility of MRI in detecting cartilage lesions and its dependence on anatomical location and lesion grade. Methods: A retrospective analysis of MRI reports and arthroscopic findings was performed on 190 consecutive patients treated in one orthopaedic department. MRI protocols were prepared by 18 radiologists from 10 different MRI centers with the use of 1.5 T magnets. The image protocols were selected by reading radiologists. Four hundred and fifty-three chondral lesions in five anatomic locations were identified during this study and graded according to the ICRS classification. Sensitivity, specificity, receiver operating characteristic (ROC), and Bangdiwala’s observer agreement charts were utilized to evaluate the diagnostic performance. Results: Only approximately 30% of MRI showed an adequate cartilage status in all anatomical locations. The sensitivity ranged from 92% in healthy cartilage to 5% in grade I lesions. The specificity differed also grossly depending on the lesion grade, reaching 96.5% in grade four lesions and 38% in healthy cartilage. The medial compartment Bangdiwala’s observer agreement charts show a gross underestimation of cartilage lesions, and the area under the curve (AUC) of ROC surpasses 0.7 only in the medial femoral condyle and patella-femoral joint. Overall, the medial compartment accuracy was significantly higher than the lateral compartment. The MRI showed correspondence of its diagnostic performance with cartilage lesion severity. Conclusion: MRI underestimates the extent of cartilage injury and evaluation of cartilage defects based on MRI should be taken with caution by orthopaedic surgeons in planning surgery. Surgical planning on MRI should take cartilage lesions under consideration, even if no cartilage lesions are reported on the MRI. Full article
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Review

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14 pages, 976 KiB  
Review
Anatomic Total Shoulder Arthroplasty versus Hemiarthroplasty for Glenohumeral Osteoarthritis: A Systematic Review and Meta-Analysis
by Filippo Migliorini, Gianluca Vecchio, Alice Baroncini, Andrea Pintore, Francesco Oliva and Nicola Maffulli
Appl. Sci. 2021, 11(21), 10112; https://doi.org/10.3390/app112110112 - 28 Oct 2021
Cited by 5 | Viewed by 2209
Abstract
Purpose: Both anatomic total shoulder arthroplasty (TSA) and shoulder hemiarthroplasty (SHA) are used for the management of end-stage glenohumeral osteoarthritis (GHOA). The present study compared TSA and SHA in terms of clinical outcome and complication rate. Methods: This meta-analysis followed the PRISMA guidelines. [...] Read more.
Purpose: Both anatomic total shoulder arthroplasty (TSA) and shoulder hemiarthroplasty (SHA) are used for the management of end-stage glenohumeral osteoarthritis (GHOA). The present study compared TSA and SHA in terms of clinical outcome and complication rate. Methods: This meta-analysis followed the PRISMA guidelines. In October 2021, the following databases were accessed: Web of Science, Google Scholar, Pubmed, Scopus. All clinical trials comparing anatomical TSA versus SHA for GHOA were considered. Results: Data from 11,027 procedures were retrieved. The mean length of the follow-up was 81.8 (16 to 223.20) months. The mean age of the patients was 61.4 ± 8.6 years, and 56.0% (5731 of 10,228 patients) were women. At last follow-up, the age-adjusted constant score was greater following TSA (p < 0.0001), as were active elevation (p < 0.0001), flexion (p < 0.0001), abduction (p < 0.0001), and American Shoulder and Elbow Surgeons Shoulder Score (p < 0.0001). Postoperative pain (p < 0.0001) and revision rate (p = 0.02) were lower in the TSA group. Conclusions: Anatomic TSA performed better than SHA in patients with GHOA. Full article
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9 pages, 250 KiB  
Review
Mesenchymal Stem Cell Applications in Spine Disorders: A Comprehensive Review
by Alice Baroncini, Jörg Eschweiler, Philipp Kobbe, Valentin Quack, Samir Smajic, Per Trobisch, Frank Hildebrand and Filippo Migliorini
Appl. Sci. 2021, 11(17), 7966; https://doi.org/10.3390/app11177966 - 28 Aug 2021
Cited by 2 | Viewed by 1981
Abstract
Mesenchymal stem cells (MSCs) are increasingly being employed in a number of orthopedic settings, in particular in the treatment of hip and knee osteoarthritis. Recently, the use MSCs has been investigated for different spine settings. However, the use of these cells is not [...] Read more.
Mesenchymal stem cells (MSCs) are increasingly being employed in a number of orthopedic settings, in particular in the treatment of hip and knee osteoarthritis. Recently, the use MSCs has been investigated for different spine settings. However, the use of these cells is not yet widespread in the clinical practice. The aim of this review was to investigate the current literature regarding the use of MSCs in different spine conditions and discuss possible future applications. In particular, degenerative disc disease is the most studied field for MSC application, and is the only one that has already reached the clinical practice, albeit not routinely. Spinal cord injuries are another extensively investigated use of MSCs: despite encouraging preliminary results, a consensus on the efficacy of stem cell therapy for spinal cord injuries has not yet been reached, and their use is still only experimental. Full article
12 pages, 543 KiB  
Review
Is Microfracture Alone Enough?
by Paul-Gabriel Borodi, Octav Marius Russu, Andrei Marian Feier, Vlad Alexandru Georgeanu, Sándor-György Zuh and Tudor Sorin Pop
Appl. Sci. 2021, 11(16), 7309; https://doi.org/10.3390/app11167309 - 9 Aug 2021
Cited by 1 | Viewed by 3655
Abstract
The technique of microfracture (MFX) was first performed 40 years ago and served for many years as the main procedure for repairing cartilage defects. There is a need to improve microfractures because the regenerated cartilage differs from the original histological aspect; it is [...] Read more.
The technique of microfracture (MFX) was first performed 40 years ago and served for many years as the main procedure for repairing cartilage defects. There is a need to improve microfractures because the regenerated cartilage differs from the original histological aspect; it is less hyaline and more fibrocartilaginous. In addition, and more importantly, the benefits do not persist and the long-term results are unsatisfactory. Adjunctive treatments include platelet-rich plasma (PRP), cell-free-based scaffolds, adipose-derived mesenchymal stem cells (ADSCs), and bone marrow aspirate concentrate (BMAC). The aim of this review was to provide an overview and a perspective of the available data regarding MFX and the principal adjunctive treatments from recent years and also to challenge the traditional MFX procedure. We found that cell-free scaffolds, platelet-rich plasma, and bone marrow aspirate concentrate, although they are relatively novel therapies, showed great potential and maintained their clinical benefits for longer periods of time compared to microfracture alone. As for chitosan-based therapy and adipose-derived mesenchymal stem cells, we were not able to form a definitive conclusion. We believe that the available data show promising results, and future research should be done on each topic discussed. Moreover, investigators involved in bone marrow stimulation techniques should focus on conducting prospective comparative studies, performing second-look arthroscopy, and rely on a single enhancement procedure that can be adequately compared with MFX alone. Full article
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