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Applied Sciences
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Cartilage Repair and Regeneration: Focus on Multi-Disciplinary Strategies
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Cartilage Repair and Regeneration: Focus on Multi-Disciplinary Strategies

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 (20 October 2021) | Viewed by 22869

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Dr. Marta Anna Szychlinska

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Guest Editor
Department of Biomedical and Biotechnological Sciences, School of Medicine, Anatomy, Histology and Movement Sciences Section, University of Catania, Via Santa Sofia 87, 95123 Catania, Italy
Interests: anatomy; morphology; histology; musculoskeletal disorders; tissue engineering; cartilage regeneration; aging; nutrition; physical activity
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Giuseppe Musumeci

E-Mail Website
Guest Editor
Department of Biomedical and Biotechnological Sciences, Anatomy, Histology and Movement Sciences Section, School of Medicine, University of Catania, 95123 Catania, Italy
Interests: anatomy; histology; kinesiology; musculoskeletal disorders; sports medicine; cartilage; osteoarthritis; physical activity; aging; nutrition
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

As widely demonstrated and known, adult articular cartilage exhibits a very poor self-healing capacity once injured. This is due to the complex multilayered morphological structure and an avascular, aneural, and hypocellular nature that characterize this tissue. A minimal damage or lesion may lead to cartilage tissue degeneration and osteoarthritis (OA) development, resulting in significant pain and disability.

Several approaches centered on cell-based therapies and cartilage engineering techniques have attempted to repair chondral or osteochondral defects that still remain a significant challenge in clinical practice. The failure in the use of these technics is often due to the improper mechanical properties of newly formed cartilage-like tissue, the early entrance of the lately differentiated chondrocytes in hypertrophic stage, characterized by a senescent-associated secretory-like phenotype, or the insufficient insertion into the host tissue, often characterized by the inflammatory, osteoarthritic milieu.

While several advances have been made in recent decades, the complexity and the multifactorial aspect of articular cartilage degeneration and a consequent, apparently unstoppable OA onset and progression suggest that a multidisciplinary approach will likely be optimal to address the challenge of preserving the articular cartilage in early stages and/or developing a functional cartilage replacements in advanced degenerative stages. This kind of approach is based on a combination of several disciplines, such as biomechanics and mechanobiology (bioreactors/moderate physical activity, etc.), innovative biomaterials functionalized with growth factors, exogenous enhancers and biomolecules exploiting pharmacological activities, cells from different sources (adult stem cells, chondrocytes, co-cultures), epigenetic modifications, functional foods, etc.

In the context of developing cartilage repair and regeneration strategies, this Special Issue’s Editor invites original contributions, review articles, communications, and concept papers that address these challenges. The suggested focus and the goal of a multidisciplinary strategy is to realize a clinically relevant tool for cartilage repair or regeneration that is more likely to be successful, obtained by controlling both the formation of a new suitable tissue replacements and the damaged joint tissues environment on the local and systemic level.

Dr. Marta Anna Szychlinska
Prof. Giuseppe Musumeci
Guest Editors

Manuscript Submission Information

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Keywords

  • cartilage repair
  • cartilage regeneration
  • tissue engineering
  • multidisciplinary strategy
  • osteoarthritis
  • bioreactors
  • mechanobiology
  • physical activity
  • functionalized biomaterials
  • functional foods

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Published Papers (6 papers)

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Editorial

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4 pages, 196 KiB  
Editorial
Cartilage Repair and Regeneration: Focus on Multi-Disciplinary Strategies—Highlight on Magneto-Responsive Techniques
by Marta Anna Szychlinska
Appl. Sci. 2021, 11(23), 11092; https://doi.org/10.3390/app112311092 - 23 Nov 2021
Viewed by 1370
Abstract
This editorial focuses on the interesting studies published within the present Special Issue and dealing with the innovative multi-disciplinary therapeutic approaches for musculoskeletal diseases. Moreover, it highlights the noteworthy magneto-responsive technique for a cartilage regeneration scope and reports some interesting studies and their [...] Read more.
This editorial focuses on the interesting studies published within the present Special Issue and dealing with the innovative multi-disciplinary therapeutic approaches for musculoskeletal diseases. Moreover, it highlights the noteworthy magneto-responsive technique for a cartilage regeneration scope and reports some interesting studies and their outcomes in this specific field. Full article
(This article belongs to the Special Issue Cartilage Repair and Regeneration: Focus on Multi-Disciplinary Strategies)

Research

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14 pages, 37570 KiB  
Article
Bioprinting of a Zonal-Specific Cell Density Scaffold: A Biomimetic Approach for Cartilage Tissue Engineering
by Angeliki Dimaraki, Pedro J. Díaz-Payno, Michelle Minneboo, Mahdiyeh Nouri-Goushki, Maryam Hosseini, Nicole Kops, Roberto Narcisi, Mohammad J. Mirzaali, Gerjo J. V. M. van Osch, Lidy E. Fratila-Apachitei and Amir A. Zadpoor
Appl. Sci. 2021, 11(17), 7821; https://doi.org/10.3390/app11177821 - 25 Aug 2021
Cited by 16 | Viewed by 4081
Abstract
The treatment of articular cartilage defects remains a significant clinical challenge. This is partially due to current tissue engineering strategies failing to recapitulate native organization. Articular cartilage is a graded tissue with three layers exhibiting different cell densities: the superficial zone having the [...] Read more.
The treatment of articular cartilage defects remains a significant clinical challenge. This is partially due to current tissue engineering strategies failing to recapitulate native organization. Articular cartilage is a graded tissue with three layers exhibiting different cell densities: the superficial zone having the highest density and the deep zone having the lowest density. However, the introduction of cell gradients for cartilage tissue engineering, which could promote a more biomimetic environment, has not been widely explored. Here, we aimed to bioprint a scaffold with different zonal cell densities to mimic the organization of articular cartilage. The scaffold was bioprinted using an alginate-based bioink containing human articular chondrocytes. The scaffold design included three cell densities, one per zone: 20 × 106 (superficial), 10 × 106 (middle), and 5 × 106 (deep) cells/mL. The scaffold was cultured in a chondrogenic medium for 25 days and analyzed by live/dead assay and histology. The live/dead analysis showed the ability to generate a zonal cell density with high viability. Histological analysis revealed a smooth transition between the zones in terms of cell distribution and a higher sulphated glycosaminoglycan deposition in the highest cell density zone. These findings pave the way toward bioprinting complex zonal cartilage scaffolds as single units, thereby advancing the translation of cartilage tissue engineering into clinical practice. Full article
(This article belongs to the Special Issue Cartilage Repair and Regeneration: Focus on Multi-Disciplinary Strategies)
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12 pages, 911 KiB  
Article
Follow-Up Study Evaluating the Long Term Outcome of ChondroMimetic in the Treatment of Osteochondral Defects in the Knee
by Agnes Berta, Matthew S. Shive, Andrew K. Lynn, Alan Getgood, Saara Totterman, Grahame Busby, Jerome Hollenstein, Gábor Vásárhelyi, Imre Kéki and László Hangody
Appl. Sci. 2020, 10(16), 5642; https://doi.org/10.3390/app10165642 - 14 Aug 2020
Cited by 3 | Viewed by 4021
Abstract
Scaffolds are thought to be a key element needed for successful cartilage repair treatments, and this prospective extension study aimed to evaluate long-term structural and clinical outcomes following osteochondral defect treatment with a cell-free biphasic scaffold. Structural outcomes were assessed using quantitative 3-D [...] Read more.
Scaffolds are thought to be a key element needed for successful cartilage repair treatments, and this prospective extension study aimed to evaluate long-term structural and clinical outcomes following osteochondral defect treatment with a cell-free biphasic scaffold. Structural outcomes were assessed using quantitative 3-D magnetic resonance imaging (MRI) and morphological segmentation to determine the percentage of defect filling and repair cartilage T2 relaxation times, and clinical outcomes were determined with the modified Cincinnati Rating System, and the Knee Injury and Osteoarthritis Outcome Score (KOOS). Seventeen subjects with osteochondral defects in the knee were treated with ChondroMimetic scaffolds, from which 15 returned for long-term evaluation at a mean follow-up of 7.9 ± 0.3 years. The defects treated were trochlear donor sites for mosaicplasty in 13 subjects, and medial femoral condyle defects in 2 subjects. MRI analysis of scaffold-treated defects found a mean total defect filling of 95.2 ± 3.6%, and a tissue mean T2 relaxation time of 52.5 ± 4.8 ms, which was identical to the T2 of ipsilateral control cartilage (52.3 ± 9.2 ms). The overall modified Cincinnati Rating System score was statistically significant from baseline (p = 0.0065), and KOOS subscales were equivalent to other cartilage repair techniques. ChondroMimetic treatment resulted in a consistently high degree of osteochondral defect filling with durable, cartilage-like repair tissue at 7.9 years, potentially associated with clinical improvement. Full article
(This article belongs to the Special Issue Cartilage Repair and Regeneration: Focus on Multi-Disciplinary Strategies)
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14 pages, 3778 KiB  
Article
Mosaicplasty versus Matrix-Assisted Autologous Chondrocyte Transplantation for Knee Cartilage Defects: A Long-Term Clinical and Imaging Evaluation
by Stefano Zaffagnini, Angelo Boffa, Luca Andriolo, Davide Reale, Maurizio Busacca, Alessandro Di Martino and Giuseppe Filardo
Appl. Sci. 2020, 10(13), 4615; https://doi.org/10.3390/app10134615 - 3 Jul 2020
Cited by 11 | Viewed by 4055
Abstract
Different surgical procedures have been proposed over the past few years to treat cartilage lesions. The aim of this study was to compare mosaicplasty and matrix-assisted autologous chondrocyte transplantation (MACT) at long-term follow-up. Forty-three patients were included: 20 mosaicplasty and 23 MACT. Patients [...] Read more.
Different surgical procedures have been proposed over the past few years to treat cartilage lesions. The aim of this study was to compare mosaicplasty and matrix-assisted autologous chondrocyte transplantation (MACT) at long-term follow-up. Forty-three patients were included: 20 mosaicplasty and 23 MACT. Patients were evaluated before and 12 years after surgery with the International Knee Documentation Committee (IKDC) subjective and objective scores for symptoms and function, and with the Tegner score for activity level. Magnetic Resonance Imaging (MRI) was used to evaluate repair tissue with the MOCART 2.0 score. Mosaicplasty and MACT showed good clinical and MRI results (IKDC subjective score 75.3 ± 21.8 and 81.8 ± 13.0, both p < 0.0005). Mosaicplasty presented a 10% reoperation rate and a 25% overall failure rate, while no failures were documented in MACT (p = 0.016). While size did not influence the results in the MACT group, mosaicplasty presented lower IKDC objective and Tegner scores in lesions bigger than 2 cm2 (p = 0.031 and p = 0.014, respectively). Mosaicplasty and MACT presented both satisfactory clinical and MRI results at long-term follow-up. However, for larger lesions, MACT presented better subjective and objective outcomes, as well as less failures, which should be considered when choosing the most suitable treatment for patients affected by knee cartilage lesions. Full article
(This article belongs to the Special Issue Cartilage Repair and Regeneration: Focus on Multi-Disciplinary Strategies)
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14 pages, 4240 KiB  
Article
Histopathological Signatures of the Femoral Head in Patients with Osteonecrosis and Potential Applications in a Multi-Targeted Approach: A Pilot Study
by Giovanna Desando, Livia Roseti, Isabella Bartolotti, Dante Dallari, Cesare Stagni and Brunella Grigolo
Appl. Sci. 2020, 10(11), 3945; https://doi.org/10.3390/app10113945 - 6 Jun 2020
Cited by 4 | Viewed by 2696
Abstract
(1) Background: Osteonecrosis (ON) of the femoral head is a disabling disease for which limited treatment options exist. Identifying therapeutic targets of its evolution could provide crucial insights into multi-targeted approaches. The aim of this pilot study was to assess the histopathological features [...] Read more.
(1) Background: Osteonecrosis (ON) of the femoral head is a disabling disease for which limited treatment options exist. Identifying therapeutic targets of its evolution could provide crucial insights into multi-targeted approaches. The aim of this pilot study was to assess the histopathological features of patients with non-traumatic femoral head (NTFH) and post-traumatic femoral head (PTFH) ON to produce a fresh vision for clinical use. (2) Methods: We got biopsies from patients with different ON stages, according to the ARCO system. Samples from multi-organ donors were used as controls. Histological and immunohistochemical evaluations were performed on the osteochondral unit. (3) Results: The PTFH group displayed several fibrotic reactions, a small stem cell pool and a lower international cartilage repair society (ICRS)-I score than NTFH, which instead presented intact cartilage similar to the controls. Immunostaining for collagen I and autotaxin confirmed these features in the PTFH group, which displayed top levels of MMP-13 involved in cartilage loss and reduced CB-2 in the underlying bone. Both groups manifested a similar pattern of apoptotic and pain mediators. (4) Conclusions: The different histopathological features suggest a multi-disciplinary and multi-targeted approach for ON. Further studies are necessary to measure the effect size to gain clinical evidence. Full article
(This article belongs to the Special Issue Cartilage Repair and Regeneration: Focus on Multi-Disciplinary Strategies)
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Review

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12 pages, 1523 KiB  
Review
New Insights on Mechanical Stimulation of Mesenchymal Stem Cells for Cartilage Regeneration
by Silvia Ravalli, Marta Anna Szychlinska, Giovanni Lauretta and Giuseppe Musumeci
Appl. Sci. 2020, 10(8), 2927; https://doi.org/10.3390/app10082927 - 23 Apr 2020
Cited by 20 | Viewed by 4689
Abstract
Successful tissue regeneration therapies require further understanding of the environment in which the cells are destined to be set. The aim is to structure approaches that aspire to a holistic view of biological systems and to scientific reliability. Mesenchymal stem cells represent a [...] Read more.
Successful tissue regeneration therapies require further understanding of the environment in which the cells are destined to be set. The aim is to structure approaches that aspire to a holistic view of biological systems and to scientific reliability. Mesenchymal stem cells represent a valuable resource for cartilage tissue engineering, due to their chondrogenic differentiation capacity. Promoting chondrogenesis, not only by growth factors but also by exogenous enhancers such as biomechanics, represents a technical enhancement. Tribological evaluation of the articular joint has demonstrated how mechanical stimuli play a pivotal role in cartilage repair and participate in the homeostasis of this tissue. Loading stresses, physiologically experienced by chondrocytes, can upregulate the production of proteins like glycosaminoglycan or collagen, fundamental for articular wellness, as well as promote and preserve cell viability. Therefore, there is a rising interest in the development of bioreactor devices that impose compression, shear stress, and hydrostatic pressure on stem cells. This strategy aims to mimic chondrogenesis and overcome complications like hypertrophic phenotyping and inappropriate mechanical features. This review will analyze the dynamics inside the joint, the natural stimuli experienced by the chondrocytes, and how the biomechanical stimuli can be applied to a stem cell culture in order to induce chondrogenesis. Full article
(This article belongs to the Special Issue Cartilage Repair and Regeneration: Focus on Multi-Disciplinary Strategies)
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