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Plath AMS, de Lima PHC, Amicone A, Bissacco EG, Mosayebi M, Berton SBR, Ferguson SJ. Toward low-friction and high-adhesion solutions: Emerging strategies for nanofibrous scaffolds in articular cartilage engineering. BIOMATERIALS ADVANCES 2025; 169:214129. [PMID: 39642717 DOI: 10.1016/j.bioadv.2024.214129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Revised: 11/28/2024] [Accepted: 11/29/2024] [Indexed: 12/09/2024]
Abstract
Aging, trauma, pathology, and poor natural tissue regeneration are the leading causes of osteoarthritis (OA), an articular cartilage disease. Electrospun scaffolds have gained attention as potential matrices for the treatment of OA because of their high degree of ECM mimicry, which suits chondrocyte migration, adhesion, and proliferation. However, none of the products recently introduced in the market are nanofiber-based. This study aimed to review the scope and tribology of nanofibrous articular cartilage scaffolds. Herein, we briefly discuss cartilage lubrication and strategies for promoting cell adhesion in electrospun materials. Next, we discuss the emerging need to study the biotribological properties of scaffolds. Finally, we review new perspectives on surface functionalization, surface segregation, Janus membranes, layer-by-layer fabrication, and nanofibrous composites. We conclude that cell adhesion and low-friction conciliation remain poorly explored in the recent literature. The topic intersection might create novelties in the field.
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Affiliation(s)
| | - Pedro Henrique Correia de Lima
- Department of Physics and Chemistry, São Paulo State University (UNESP), Av. Brasil, 56, 15385007 Ilha Solteira, Brazil.
| | - Alessio Amicone
- Institute for Biomechanics, ETH Zurich, Gloriastrasse 37-39, 8092 Zurich, Switzerland
| | | | - Mahdieh Mosayebi
- Institute for Biomechanics, ETH Zurich, Gloriastrasse 37-39, 8092 Zurich, Switzerland
| | | | - Stephen J Ferguson
- Institute for Biomechanics, ETH Zurich, Gloriastrasse 37-39, 8092 Zurich, Switzerland
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Meinert C, Weekes A, Chang CW, Schrobback K, Gelmi A, Stevens MM, Hutmacher DW, Klein TJ. Crosslinking substrate regulates frictional properties of tissue-engineered cartilage and chondrocyte response to loading. COMMUNICATIONS MATERIALS 2025; 6:55. [PMID: 40162094 PMCID: PMC11949837 DOI: 10.1038/s43246-025-00781-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Accepted: 03/14/2025] [Indexed: 04/02/2025]
Abstract
Hydrogels are frequently used in regenerative medicine due to their hydrated, tissue-compatible nature, and tuneable mechanics. While many strategies enable bulk mechanical modulation, little attention is given to tuning surface tribology, and its impact on cellular behavior under mechanical stimuli. Here, we demonstrate that photocrosslinking hydrogels on hydrophobic substrates leads to significant, long-lasting reductions in surface friction, ideal for cartilage tissue regeneration. Gelatin methacryloyl and hyaluronic acid methacrylate hydrogels photocrosslinked on polytetrafluoroethylene possess more hydrated, lubricious surfaces, with lower friction coefficients and crosslinking densities than those crosslinked on glass. This facilitated self-lubrication via water exudation, limiting shear during biaxial stimulation. When subject to intermittent biaxial loading mimicking joint movement, low-friction chondrocyte-laden neo-tissues formed superior hyaline cartilage, confirming the benefits of reduced friction on tissue development. Finally, in situ photocrosslinking enabled precise hydrogel formation in a full-thickness cartilage defect, highlighting the clinical potential and emphasizing the importance of crosslinking substrate in regenerative medicine.
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Affiliation(s)
- Christoph Meinert
- Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, QLD Australia
- Gelomics Pty Ltd., Brisbane, QLD Australia
| | - Angus Weekes
- Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, QLD Australia
- Max Planck Queensland Centre (MPQC) for the Materials Science of Extracellular Matrices, Queensland University of Technology (QUT), Brisbane, QLD Australia
- School of Mechanical, Medical and Process Engineering, Faculty of Engineering, Queensland University of Technology (QUT), Brisbane, QLD Australia
| | - Chun-Wei Chang
- Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, QLD Australia
- Max Planck Queensland Centre (MPQC) for the Materials Science of Extracellular Matrices, Queensland University of Technology (QUT), Brisbane, QLD Australia
| | - Karsten Schrobback
- Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology (QUT), Brisbane, QLD Australia
| | - Amy Gelmi
- Department of Materials, Imperial College London, London, UK
| | - Molly M. Stevens
- Department of Materials, Imperial College London, London, UK
- Department of Bioengineering, Imperial College London, London, UK
- Institute of Biomedical Engineering, Imperial College London, London, UK
| | - Dietmar W. Hutmacher
- Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, QLD Australia
- Max Planck Queensland Centre (MPQC) for the Materials Science of Extracellular Matrices, Queensland University of Technology (QUT), Brisbane, QLD Australia
- School of Mechanical, Medical and Process Engineering, Faculty of Engineering, Queensland University of Technology (QUT), Brisbane, QLD Australia
| | - Travis J. Klein
- Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, QLD Australia
- School of Mechanical, Medical and Process Engineering, Faculty of Engineering, Queensland University of Technology (QUT), Brisbane, QLD Australia
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Fares MY, Daher M, Boufadel P, Haikal E, Haj Shehade T, Koa J, Khan AZ, Abboud JA. The use of autologous chondrocyte transplantation for the treatment of osteoarthritis: a systematic review of clinical trials. Cell Tissue Bank 2024; 26:5. [PMID: 39729188 DOI: 10.1007/s10561-024-10154-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Accepted: 12/12/2024] [Indexed: 12/28/2024]
Abstract
Tissue engineering and cartilage transplantation constitute an evolving field in the treatment of osteoarthritis, with therapeutic and clinical promise shown in autologous chondrocyte implantation. The aim of this systematic review is to explore current clinical trials that utilized autologous chondrocyte transplantation (ACT) and assess its efficacy in the treatment of osteoarthritis. PubMed, Ovid MEDLINE, and Google-Scholar (pages 1-20) were searched up until February 2023. Inclusion criteria consisted of clinical trials that involve autologous cartilage transplantation for the treatment of osteoarthritis. Clinical, imaging, arthroscopic, and histologic outcomes were assessed. A total of 15 clinical trials, involving 851 participants, were included in the study. All trials utilized ACT in the treatment of knee osteoarthritis through varying scaffolds: collagen-based (10 trials), polymer-based (2 trials), hyaluronic-acid based (2 trials), and spheroid technology (1 trial). Clinical improvement of patients undergoing ACT was noted in 14 trials; five showed superior clinical outcomes compared to the control group, while one showed inferiority compared to mesenchymal stem cells. Postoperative imaging was utilized to assess the degree of cartilage regeneration in 11 trials. Ten trials showed signs of cartilage recovery with ACT, four trials showed no difference, and two showed worse outcomes when compared to controls. Second-look-arthroscopy was performed in three trials, which reported varying degrees of improvement in cartilage regeneration. Histologic analysis was performed in four trials and generally showed promising results. While improved clinical outcomes were demonstrated, conflicting findings in postoperative outcome analysis raise questions about the unequivocal utility of ACT. Additional research with control groups, randomization, and appropriate blinding is required.
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Affiliation(s)
- Mohamad Y Fares
- Division of Shoulder and Elbow Surgery, Rothman Orthopaedic Institute, Philadelphia, PA, USA.
- Southern California Permanente Medical Group, Panorama City, CA, USA.
| | - Mohammad Daher
- Division of Shoulder and Elbow Surgery, Rothman Orthopaedic Institute, Philadelphia, PA, USA
- Southern California Permanente Medical Group, Panorama City, CA, USA
| | - Peter Boufadel
- Division of Shoulder and Elbow Surgery, Rothman Orthopaedic Institute, Philadelphia, PA, USA
- Southern California Permanente Medical Group, Panorama City, CA, USA
| | - Emil Haikal
- Division of Shoulder and Elbow Surgery, Rothman Orthopaedic Institute, Philadelphia, PA, USA
- Southern California Permanente Medical Group, Panorama City, CA, USA
| | - Tarek Haj Shehade
- Division of Shoulder and Elbow Surgery, Rothman Orthopaedic Institute, Philadelphia, PA, USA
- Southern California Permanente Medical Group, Panorama City, CA, USA
| | - Jonathan Koa
- Division of Shoulder and Elbow Surgery, Rothman Orthopaedic Institute, Philadelphia, PA, USA
- Southern California Permanente Medical Group, Panorama City, CA, USA
| | - Adam Z Khan
- Division of Shoulder and Elbow Surgery, Rothman Orthopaedic Institute, Philadelphia, PA, USA
- Southern California Permanente Medical Group, Panorama City, CA, USA
| | - Joseph A Abboud
- Division of Shoulder and Elbow Surgery, Rothman Orthopaedic Institute, Philadelphia, PA, USA
- Southern California Permanente Medical Group, Panorama City, CA, USA
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A S S, G MK. In vitro chondrogenic potential of marine biocomposite hydrogel construct for cartilage tissue engineering. JOURNAL OF BIOMATERIALS SCIENCE. POLYMER EDITION 2024; 35:2845-2866. [PMID: 39431438 DOI: 10.1080/09205063.2024.2391223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Accepted: 08/07/2024] [Indexed: 10/22/2024]
Abstract
Cartilage tissue engineering (CTE) is a field of regenerative medicine focused on constructing ideal substitutes for injured cartilage by effectively combining cells, scaffolds, and stimulatory factors. In vitro CTE employing chondrocytes and biopolymer-based hydrogels has the potential to repair damaged cartilage. In this research, primary chondrocytes were extracted from the rib cartilage of rats and seeded on a hydrogel construct named HACF, which is made from hydroxyapatite, alginate, chitosan, and fucoidan. We then evaluated in vitro chondrogenesis on HACF cartilage construct. The results revealed that the primary chondrocytes were successfully isolated from rat rib cartilage by collagenase D digestion and HACF cartilage construct was effectively synthesized. Chondrocyte viability and its differentiation inside the scaffold HACF were determined by MTT assay, NRU assay, live/dead assay, DAPI nuclear staining, flow cytometry analysis (FCA), mRNA expression studies, and quantification of extracellular matrix components in the HACF scaffold. The findings indicated excellent chondrocyte viability within the HACF scaffold, with no noticeable changes in morphology. Apoptosis was not detected in the chondrocytes cultured on these hydrogels, as confirmed by DAPI staining, live/dead assay, and FCA. This demonstrates that the cells were capable of proliferating, dividing, multiplying, and maintaining their integrity on HACF scaffold. The results also showed more collagen deposition and glycosaminoglycan synthesis showing the good health of chondrocytes on the HACF construct. It indicates that HACF is an ideal scaffold supporting stable cartilage matrix production, highlighting its suitability for cartilage tissue engineering.
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Affiliation(s)
- Sumayya A S
- Assistant Professor, Department of Biochemistry, T.K.M. College of Arts and Science, kollam-5, kerala, India
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5
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Semitela A, Marques PAAP, Completo A. Strategies to engineer articular cartilage with biomimetic zonal features: a review. Biomater Sci 2024; 12:5961-6005. [PMID: 39463257 DOI: 10.1039/d4bm00579a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/29/2024]
Abstract
Articular cartilage (AC) is a highly specialized tissue with restricted ability for self-regeneration, given its avascular and acellular nature. Although a considerable number of surgical treatments is available for the repair, reconstruction, and regeneration of AC defects, most of them do not prioritize the development of engineered cartilage with zonal stratification derived from biomimetic biochemical, biomechanical and topographic cues. In the absence of these zonal elements, engineered cartilage will exhibit increased susceptibility to failure and will neither be able to withstand the mechanical loading to which AC is subjected nor will it integrate well with the surrounding tissue. In this regard, new breakthroughs in the development of hierarchical stratified engineered cartilage are highly sought after. Initially, this review provides a comprehensive analysis of the composition and zonal organization of AC, aiming to enhance our understanding of the significance of the structure of AC for its function. Next, we direct our attention towards the existing in vitro and in vivo studies that introduce zonal elements in engineered cartilage to elicit appropriate AC regeneration by employing tissue engineering strategies. Finally, the advantages, challenges, and future perspectives of these approaches are presented.
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Affiliation(s)
- Angela Semitela
- Centre of Mechanical Technology and Automation (TEMA), Department of Mechanical Engineering, University of Aveiro, 3810-193 Aveiro, Portugal.
| | - Paula A A P Marques
- Centre of Mechanical Technology and Automation (TEMA), Department of Mechanical Engineering, University of Aveiro, 3810-193 Aveiro, Portugal.
| | - António Completo
- Centre of Mechanical Technology and Automation (TEMA), Department of Mechanical Engineering, University of Aveiro, 3810-193 Aveiro, Portugal.
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6
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Jia Y, Le H, Wang X, Zhang J, Liu Y, Ding J, Zheng C, Chang F. Double-edged role of mechanical stimuli and underlying mechanisms in cartilage tissue engineering. Front Bioeng Biotechnol 2023; 11:1271762. [PMID: 38053849 PMCID: PMC10694366 DOI: 10.3389/fbioe.2023.1271762] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Accepted: 10/11/2023] [Indexed: 12/07/2023] Open
Abstract
Mechanical stimuli regulate the chondrogenic differentiation of mesenchymal stem cells and the homeostasis of chondrocytes, thus affecting implant success in cartilage tissue engineering. The mechanical microenvironment plays fundamental roles in the maturation and maintenance of natural articular cartilage, and the progression of osteoarthritis Hence, cartilage tissue engineering attempts to mimic this environment in vivo to obtain implants that enable a superior regeneration process. However, the specific type of mechanical loading, its optimal regime, and the underlying molecular mechanisms are still under investigation. First, this review delineates the composition and structure of articular cartilage, indicating that the morphology of chondrocytes and components of the extracellular matrix differ from each other to resist forces in three top-to-bottom overlapping zones. Moreover, results from research experiments and clinical trials focusing on the effect of compression, fluid shear stress, hydrostatic pressure, and osmotic pressure are presented and critically evaluated. As a key direction, the latest advances in mechanisms involved in the transduction of external mechanical signals into biological signals are discussed. These mechanical signals are sensed by receptors in the cell membrane, such as primary cilia, integrins, and ion channels, which next activate downstream pathways. Finally, biomaterials with various modifications to mimic the mechanical properties of natural cartilage and the self-designed bioreactors for experiment in vitro are outlined. An improved understanding of biomechanically driven cartilage tissue engineering and the underlying mechanisms is expected to lead to efficient articular cartilage repair for cartilage degeneration and disease.
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Affiliation(s)
- Yao Jia
- Department of Orthopedics, The Second Hospital of Jilin University, Jilin, China
- The Second Bethune Clinical Medical College of Jilin University, Jilin, China
| | - Hanxiang Le
- Department of Orthopedics, The Second Hospital of Jilin University, Jilin, China
- The Fourth Treatment Area of Trauma Hip Joint Surgery Department, Tianjin Hospital, Tianjin, China
| | - Xianggang Wang
- Department of Orthopedics, The Second Hospital of Jilin University, Jilin, China
| | - Jiaxin Zhang
- Department of Orthopedics, The Second Hospital of Jilin University, Jilin, China
| | - Yan Liu
- The Second Bethune Clinical Medical College of Jilin University, Jilin, China
| | - Jiacheng Ding
- The Second Bethune Clinical Medical College of Jilin University, Jilin, China
| | - Changjun Zheng
- Department of Orthopedics, The Second Hospital of Jilin University, Jilin, China
| | - Fei Chang
- Department of Orthopedics, The Second Hospital of Jilin University, Jilin, China
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7
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Zhang Z, Mu Y, Zhou H, Yao H, Wang DA. Cartilage Tissue Engineering in Practice: Preclinical Trials, Clinical Applications, and Prospects. TISSUE ENGINEERING. PART B, REVIEWS 2023; 29:473-490. [PMID: 36964757 DOI: 10.1089/ten.teb.2022.0190] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/26/2023]
Abstract
Articular cartilage defects significantly compromise the quality of life in the global population. Although many strategies are needed to repair articular cartilage, including microfracture, autologous osteochondral transplantation, and osteochondral allograft, the therapeutic effects remain suboptimal. In recent years, with the development of cartilage tissue engineering, scientists have continuously improved the formulations of therapeutic cells, biomaterial-based scaffolds, and biological factors, which have opened new avenues for better therapeutics of cartilage lesions. This review focuses on advances in cartilage tissue engineering, particularly in preclinical trials and clinical applications, prospects, and challenges.
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Affiliation(s)
- Zhen Zhang
- Department of Biomedical Engineering, City University of Hong Kong, Kowloon, Hong Kong SAR
| | - Yulei Mu
- Department of Biomedical Engineering, City University of Hong Kong, Kowloon, Hong Kong SAR
| | - Huiqun Zhou
- Department of Biomedical Engineering, City University of Hong Kong, Kowloon, Hong Kong SAR
| | - Hang Yao
- School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, P.R. China
| | - Dong-An Wang
- Department of Biomedical Engineering, City University of Hong Kong, Kowloon, Hong Kong SAR
- Karolinska Institutet Ming Wai Lau Centre for Reparative Medicine, HKSTP, Sha Tin, Hong Kong SAR
- Shenzhen Research Institute, City University of Hong Kong, Shenzhen, P.R. China
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8
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Chen L, Zhou C, Jiang C, Huang X, Liu Z, Zhang H, Liang W, Zhao J. Translation of nanotechnology-based implants for orthopedic applications: current barriers and future perspective. Front Bioeng Biotechnol 2023; 11:1206806. [PMID: 37675405 PMCID: PMC10478008 DOI: 10.3389/fbioe.2023.1206806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Accepted: 07/21/2023] [Indexed: 09/08/2023] Open
Abstract
The objective of bioimplant engineering is to develop biologically compatible materials for restoring, preserving, or altering damaged tissues and/or organ functions. The variety of substances used for orthopedic implant applications has been substantially influenced by modern material technology. Therefore, nanomaterials can mimic the surface properties of normal tissues, including surface chemistry, topography, energy, and wettability. Moreover, the new characteristics of nanomaterials promote their application in sustaining the progression of many tissues. The current review establishes a basis for nanotechnology-driven biomaterials by demonstrating the fundamental design problems that influence the success or failure of an orthopedic graft, cell adhesion, proliferation, antimicrobial/antibacterial activity, and differentiation. In this context, extensive research has been conducted on the nano-functionalization of biomaterial surfaces to enhance cell adhesion, differentiation, propagation, and implant population with potent antimicrobial activity. The possible nanomaterials applications (in terms of a functional nanocoating or a nanostructured surface) may resolve a variety of issues (such as bacterial adhesion and corrosion) associated with conventional metallic or non-metallic grafts, primarily for optimizing implant procedures. Future developments in orthopedic biomaterials, such as smart biomaterials, porous structures, and 3D implants, show promise for achieving the necessary characteristics and shape of a stimuli-responsive implant. Ultimately, the major barriers to the commercialization of nanotechnology-derived biomaterials are addressed to help overcome the limitations of current orthopedic biomaterials in terms of critical fundamental factors including cost of therapy, quality, pain relief, and implant life. Despite the recent success of nanotechnology, there are significant hurdles that must be overcome before nanomedicine may be applied to orthopedics. The objective of this review was to provide a thorough examination of recent advancements, their commercialization prospects, as well as the challenges and potential perspectives associated with them. This review aims to assist healthcare providers and researchers in extracting relevant data to develop translational research within the field. In addition, it will assist the readers in comprehending the scope and gaps of nanomedicine's applicability in the orthopedics field.
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Affiliation(s)
- Long Chen
- Department of Orthopedics, Affiliated Hospital of Shaoxing University, Shaoxing, Zhejiang, China
| | - Chao Zhou
- Department of Orthopedics, Zhoushan Guanghua Hospital, Zhoushan, China
| | - Chanyi Jiang
- Department of Pharmacy, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan, China
| | - Xiaogang Huang
- Department of Orthopedics, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan, Zhejiang, China
| | - Zunyong Liu
- Department of Orthopedics, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan, Zhejiang, China
| | - Hengjian Zhang
- Department of Orthopedics, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan, Zhejiang, China
| | - Wenqing Liang
- Department of Orthopedics, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan, Zhejiang, China
| | - Jiayi Zhao
- Department of Orthopedics, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan, Zhejiang, China
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Singh D, Lindsay S, Gurbaxani S, Crawford A, Claeyssens F. Elastomeric Porous Poly(glycerol sebacate) Methacrylate (PGSm) Microspheres as 3D Scaffolds for Chondrocyte Culture and Cartilage Tissue Engineering. Int J Mol Sci 2023; 24:10445. [PMID: 37445620 DOI: 10.3390/ijms241310445] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 06/12/2023] [Accepted: 06/16/2023] [Indexed: 07/15/2023] Open
Abstract
Cartilage defects can be difficult to treat; therefore, tissue engineering of cartilage is emerging as a promising potential therapy. One interesting area of research explores the delivery of cells to the cartilage defect via scaffold-based cell delivery vehicles and microsurgery. This study explores the use of novel poly(glycerol sebacate) methacrylate (PGSm)-polymerised high internal phase emulsion (polyHIPE) microspheres as scaffolds with embedded cells for cartilage tissue engineering. Porous microsphere scaffolds (100 µm-1 mm diameter) were produced from emulsions consisting of water and a methacrylate-based photocurable resin of poly(glycerol sebacate). These resins were used in conjunction with a T-junction fluidic device and an ultraviolet (UV) curing lamp to produce porous microspheres with a tuneable size. This technique produced biodegradable PGSm microspheres with similar mechanical properties to cartilage. We further explore these microspheres as scaffolds for three-dimensional culture of chondrocytes. The microspheres proved to be very efficient scaffolds for primary chondrocyte culture and were covered by a dense extracellular matrix (ECM) network during the culture period, creating a tissue disk. The presence of glycosaminoglycans (GAGs) and collagen-II was confirmed, highlighting the utility of the PGSm microspheres as a delivery vehicle for chondrocytes. A number of imaging techniques were utilised to analyse the tissue disk and develop methodologies to characterise the resultant tissue. This study highlights the utility of porous PGSm microspheres for cartilage tissue engineering.
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Affiliation(s)
- Dharaminder Singh
- Kroto Research Institute, Department of Materials Science and Engineering, The University of Sheffield, Broad Lane, Sheffield S3 7HQ, UK
| | - Sarah Lindsay
- School of Clinical Dentistry, The University of Sheffield, Claremont Crescent, Sheffield S10 2TN, UK
| | - Shruti Gurbaxani
- School of Clinical Dentistry, The University of Sheffield, Claremont Crescent, Sheffield S10 2TN, UK
| | - Aileen Crawford
- School of Clinical Dentistry, The University of Sheffield, Claremont Crescent, Sheffield S10 2TN, UK
| | - Frederik Claeyssens
- Kroto Research Institute, Department of Materials Science and Engineering, The University of Sheffield, Broad Lane, Sheffield S3 7HQ, UK
- Insigneo Institute for in Silico Medicine, The University of Sheffield, Sheffield S10 2TN, UK
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10
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Kim B, Bouklas N, Cohen I, Bonassar LJ. Instabilities induced by mechanical loading determine the viability of chondrocytes grown on porous scaffolds. J Biomech 2023; 152:111591. [PMID: 37088031 DOI: 10.1016/j.jbiomech.2023.111591] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 02/08/2023] [Accepted: 04/11/2023] [Indexed: 04/25/2023]
Abstract
Tissue-engineered cartilage constructs have shown promise to treat focal cartilage defects in multiple clinical studies. Notably, products in clinical use or in late-stage clinical trials often utilize porous collagen scaffolds to provide mechanical support and attachment sites for chondrocytes. Under loading, both the local mechanical responses of collagen scaffolds and the corresponding cellular outcomes are poorly understood, despite their wide use. As such, the architecture of collagen scaffolds varies significantly among tissue-engineered cartilage products, but the effects of such architectures on construct mechanics and cell viability are not well understood. This study investigated the effects of local mechanical responses of collagen scaffolds on chondrocyte viability in tissue-engineered cartilage constructs. We utilized fast confocal microscopy combined with a strain mapping technique to analyze the architecture-dependent instabilities under quasi-static loading and subsequent chondrocyte death in honeycomb and sponge scaffolds. More specifically, we compared the isotropic and the orthotropic planes for each type of collagen scaffold. Under compression, both planes exhibited elastic, buckled, and densified deformation modes. In both loading directions, cell death was minimal in regions that experienced elastic deformation mode and a trend of increase in buckled mode. More interestingly, we saw a significant increase in cell death in densified mode. Overall, this study suggests that local instabilities are directly correlated to chondrocyte death in tissue-engineered cartilage constructs, highlighting the importance of understanding the architecture-dependent local mechanical responses under loading.
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Affiliation(s)
- Byumsu Kim
- Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, United States
| | - Nikolaos Bouklas
- Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, United States
| | - Itai Cohen
- Department of Physics, Cornell University, Ithaca, NY, United States
| | - Lawrence J Bonassar
- Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, United States; Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, United States.
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11
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Tolabi H, Davari N, Khajehmohammadi M, Malektaj H, Nazemi K, Vahedi S, Ghalandari B, Reis RL, Ghorbani F, Oliveira JM. Progress of Microfluidic Hydrogel-Based Scaffolds and Organ-on-Chips for the Cartilage Tissue Engineering. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2023:e2208852. [PMID: 36633376 DOI: 10.1002/adma.202208852] [Citation(s) in RCA: 39] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 12/09/2022] [Indexed: 05/09/2023]
Abstract
Cartilage degeneration is among the fundamental reasons behind disability and pain across the globe. Numerous approaches have been employed to treat cartilage diseases. Nevertheless, none have shown acceptable outcomes in the long run. In this regard, the convergence of tissue engineering and microfabrication principles can allow developing more advanced microfluidic technologies, thus offering attractive alternatives to current treatments and traditional constructs used in tissue engineering applications. Herein, the current developments involving microfluidic hydrogel-based scaffolds, promising structures for cartilage regeneration, ranging from hydrogels with microfluidic channels to hydrogels prepared by the microfluidic devices, that enable therapeutic delivery of cells, drugs, and growth factors, as well as cartilage-related organ-on-chips are reviewed. Thereafter, cartilage anatomy and types of damages, and present treatment options are briefly overviewed. Various hydrogels are introduced, and the advantages of microfluidic hydrogel-based scaffolds over traditional hydrogels are thoroughly discussed. Furthermore, available technologies for fabricating microfluidic hydrogel-based scaffolds and microfluidic chips are presented. The preclinical and clinical applications of microfluidic hydrogel-based scaffolds in cartilage regeneration and the development of cartilage-related microfluidic chips over time are further explained. The current developments, recent key challenges, and attractive prospects that should be considered so as to develop microfluidic systems in cartilage repair are highlighted.
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Affiliation(s)
- Hamidreza Tolabi
- New Technologies Research Center (NTRC), Amirkabir University of Technology, Tehran, 15875-4413, Iran
- Department of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran, 15875-4413, Iran
| | - Niyousha Davari
- Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, 143951561, Iran
| | - Mehran Khajehmohammadi
- Department of Mechanical Engineering, Faculty of Engineering, Yazd University, Yazd, 89195-741, Iran
- Medical Nanotechnology and Tissue Engineering Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, 8916877391, Iran
| | - Haniyeh Malektaj
- Department of Materials and Production, Aalborg University, Fibigerstraede 16, Aalborg, 9220, Denmark
| | - Katayoun Nazemi
- Drug Delivery, Disposition and Dynamics Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, 3052, Australia
| | - Samaneh Vahedi
- Department of Material Science and Engineering, Faculty of Engineering, Imam Khomeini International University, Qazvin, 34149-16818, Iran
| | - Behafarid Ghalandari
- State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China
| | - Rui L Reis
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, Guimarães, 4805-017, Portugal
- ICVS/3B's-PT Government Associate Laboratory, Braga, Guimarães, 4805-017, Portugal
| | - Farnaz Ghorbani
- Institute of Biomaterials, University of Erlangen-Nuremberg, Cauerstrasse 6, 91058, Erlangen, Germany
| | - Joaquim Miguel Oliveira
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, Guimarães, 4805-017, Portugal
- ICVS/3B's-PT Government Associate Laboratory, Braga, Guimarães, 4805-017, Portugal
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12
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Haq-Siddiqi NA, Britton D, Kim Montclare J. Protein-engineered biomaterials for cartilage therapeutics and repair. Adv Drug Deliv Rev 2023; 192:114647. [PMID: 36509172 DOI: 10.1016/j.addr.2022.114647] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Revised: 10/17/2022] [Accepted: 12/05/2022] [Indexed: 12/13/2022]
Abstract
Cartilage degeneration and injury are major causes of pain and disability that effect millions, and yet treatment options for conditions like osteoarthritis (OA) continue to be mainly palliative or involve complete replacement of injured joints. Several biomaterial strategies have been explored to address cartilage repair either by the delivery of therapeutics or as support for tissue repair, however the complex structure of cartilage tissue, its mechanical needs, and lack of regenerative capacity have hindered this goal. Recent advances in synthetic biology have opened new possibilities for engineered proteins to address these unique needs. Engineered protein and peptide-based materials benefit from inherent biocompatibility and nearly unlimited tunability as they utilize the body's natural building blocks to fabricate a variety of supramolecular structures. The pathophysiology and needs of OA cartilage are presented here, along with an overview of the current state of the art and next steps for protein-engineered repair strategies for cartilage.
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Affiliation(s)
- Nada A Haq-Siddiqi
- Department of Chemical and Biomolecular Engineering, New York University Tandon School of Engineering, Brooklyn, NY 11201, United States
| | - Dustin Britton
- Department of Chemical and Biomolecular Engineering, New York University Tandon School of Engineering, Brooklyn, NY 11201, United States
| | - Jin Kim Montclare
- Department of Chemical and Biomolecular Engineering, New York University Tandon School of Engineering, Brooklyn, NY 11201, United States; Department of Chemistry, New York University, New York 10003, United States; Department of Radiology, New York University Grossman School of Medicine, New York 10016, United States; Department of Biomaterials, NYU College of Dentistry, New York, NY 10010, United States; Department of Biomedical Engineering, New York University Tandon School of Engineering, Brooklyn, NY 11201, United States.
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13
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Janacova V, Szomolanyi P, Kirner A, Trattnig S, Juras V. Adjacent cartilage tissue structure after successful transplantation: a quantitative MRI study using T 2 mapping and texture analysis. Eur Radiol 2022; 32:8364-8375. [PMID: 35737095 DOI: 10.1007/s00330-022-08897-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 05/03/2022] [Accepted: 05/19/2022] [Indexed: 11/28/2022]
Abstract
OBJECTIVES The aim of this study was to assess the texture of repair tissue and tissue adjacent to the repair site after matrix-associated chondrocyte transplantation (MACT) of the knee using gray-level co-occurrence matrix (GLCM) texture analysis of T2 quantitative maps. METHODS Twenty patients derived from the MRI sub-study of multicenter, single-arm phase III study underwent examination on a 3 T MR scanner, including a T2 mapping sequence 12 and 24 months after MACT. Changes between the time points in mean T2 values and 20 GLCM features were assessed for repair tissue, adjacent tissue, and reference cartilage. Differences in T2 values and selected GLCM features between the three cartilage sites at two time points were analyzed using linear mixed-effect models. RESULTS A significant decrease in T2 values after MACT, between time points, was observed only in repair cartilage (p < 0.001). Models showed significant differences in GLCM features between repair tissue and reference cartilage, namely, autocorrelation (p < 0.001), correlation (p = 0.015), homogeneity (p = 0.002), contrast (p < 0.001), and difference entropy (p = 0.047). The effect of time was significant in a majority of models with regard to GLCM features (except autocorrelation) (p ≤ 0.001). Values in repair and adjacent tissue became similar to reference tissue over time. CONCLUSIONS GLCM is a useful add-on to T2 mapping in the evaluation of knee cartilage after MACT by increasing the sensitivity to changes in cartilage structure. The results suggest that cartilage tissue adjacent to the repair site heals along with the cartilage implant. KEY POINTS • GLCM is a useful add-on to T2 mapping in the evaluation of knee cartilage after MACT by increasing the sensitivity to changes in cartilage structure. • Repair and adjacent tissue became similar to reference tissue over time. • The results suggest that cartilage tissue adjacent to the repair site heals along with the cartilage implant.
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Affiliation(s)
- Veronika Janacova
- High-Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, BT32, Lazarettgasse 14, 1090, Vienna, Austria
| | - Pavol Szomolanyi
- High-Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, BT32, Lazarettgasse 14, 1090, Vienna, Austria.,Institute of Measurement Science, Slovak Academy of Sciences, Bratislava, Slovakia
| | - Alexandra Kirner
- TETEC Tissue Engineering Technologies AG, Aspenhaustraße 18, 72770, Reutlingen, Germany
| | - Siegfried Trattnig
- High-Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, BT32, Lazarettgasse 14, 1090, Vienna, Austria. .,CD Laboratory for Clinical Molecular MR Imaging, Vienna, Austria. .,Austrian Cluster for Tissue Regeneration, Vienna, Austria. .,Institute for Clinical Molecular MRI in the Musculoskeletal System, Karl Landsteiner Society, Vienna, Austria.
| | - Vladimir Juras
- High-Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, BT32, Lazarettgasse 14, 1090, Vienna, Austria
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14
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Ashammakhi N, GhavamiNejad A, Tutar R, Fricker A, Roy I, Chatzistavrou X, Hoque Apu E, Nguyen KL, Ahsan T, Pountos I, Caterson EJ. Highlights on Advancing Frontiers in Tissue Engineering. TISSUE ENGINEERING. PART B, REVIEWS 2022; 28:633-664. [PMID: 34210148 PMCID: PMC9242713 DOI: 10.1089/ten.teb.2021.0012] [Citation(s) in RCA: 52] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Accepted: 07/15/2021] [Indexed: 01/05/2023]
Abstract
The field of tissue engineering continues to advance, sometimes in exponential leaps forward, but also sometimes at a rate that does not fulfill the promise that the field imagined a few decades ago. This review is in part a catalog of success in an effort to inform the process of innovation. Tissue engineering has recruited new technologies and developed new methods for engineering tissue constructs that can be used to mitigate or model disease states for study. Key to this antecedent statement is that the scientific effort must be anchored in the needs of a disease state and be working toward a functional product in regenerative medicine. It is this focus on the wildly important ideas coupled with partnered research efforts within both academia and industry that have shown most translational potential. The field continues to thrive and among the most important recent developments are the use of three-dimensional bioprinting, organ-on-a-chip, and induced pluripotent stem cell technologies that warrant special attention. Developments in the aforementioned areas as well as future directions are highlighted in this article. Although several early efforts have not come to fruition, there are good examples of commercial profitability that merit continued investment in tissue engineering. Impact statement Tissue engineering led to the development of new methods for regenerative medicine and disease models. Among the most important recent developments in tissue engineering are the use of three-dimensional bioprinting, organ-on-a-chip, and induced pluripotent stem cell technologies. These technologies and an understanding of them will have impact on the success of tissue engineering and its translation to regenerative medicine. Continued investment in tissue engineering will yield products and therapeutics, with both commercial importance and simultaneous disease mitigation.
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Affiliation(s)
- Nureddin Ashammakhi
- Department of Bioengineering, Henry Samueli School of Engineering, University of California, Los Angeles, California, USA
- Department of Biomedical Engineering, College of Engineering, Michigan State University, Michigan, USA
| | - Amin GhavamiNejad
- Advanced Pharmaceutics and Drug Delivery Laboratory, Leslie L. Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada
| | - Rumeysa Tutar
- Department of Chemistry, Faculty of Engineering, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Annabelle Fricker
- Department of Materials Science and Engineering, Faculty of Engineering, University of Sheffield, Sheffield, United Kingdom
| | - Ipsita Roy
- Department of Materials Science and Engineering, Faculty of Engineering, University of Sheffield, Sheffield, United Kingdom
- Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom
| | - Xanthippi Chatzistavrou
- Department of Chemical Engineering and Material Science, College of Engineering, Michigan State University, East Lansing, Michigan, USA
| | - Ehsanul Hoque Apu
- Department of Bioengineering, Henry Samueli School of Engineering, University of California, Los Angeles, California, USA
| | - Kim-Lien Nguyen
- Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, California, USA
- Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, and VA Greater Los Angeles Healthcare System, Los Angeles, California, USA
| | - Taby Ahsan
- RoosterBio, Inc., Frederick, Maryland, USA
| | - Ippokratis Pountos
- Academic Department of Trauma and Orthopaedics, University of Leeds, Leeds, United Kingdom
| | - Edward J. Caterson
- Division of Plastic Surgery, Department of Surgery, Nemours/Alfred I. du Pont Hospital for Children, Wilmington, Delaware, USA
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15
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Terzopoulou Z, Zamboulis A, Koumentakou I, Michailidou G, Noordam MJ, Bikiaris DN. Biocompatible Synthetic Polymers for Tissue Engineering Purposes. Biomacromolecules 2022; 23:1841-1863. [PMID: 35438479 DOI: 10.1021/acs.biomac.2c00047] [Citation(s) in RCA: 88] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Synthetic polymers have been an integral part of modern society since the early 1960s. Besides their most well-known applications to the public, such as packaging, construction, textiles and electronics, synthetic polymers have also revolutionized the field of medicine. Starting with the first plastic syringe developed in 1955 to the complex polymeric materials used in the regeneration of tissues, their contributions have never been more prominent. Decades of research on polymeric materials, stem cells, and three-dimensional printing contributed to the rapid progress of tissue engineering and regenerative medicine that envisages the potential future of organ transplantations. This perspective discusses the role of synthetic polymers in tissue engineering, their design and properties in relation to each type of application. Additionally, selected recent achievements of tissue engineering using synthetic polymers are outlined to provide insight into how they will contribute to the advancement of the field in the near future. In this way, we aim to provide a guide that will help scientists with synthetic polymer design and selection for different tissue engineering applications.
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Affiliation(s)
- Zoi Terzopoulou
- Laboratory of Chemistry and Technology of Polymers and Dyes, Department of Chemistry, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece
| | - Alexandra Zamboulis
- Laboratory of Chemistry and Technology of Polymers and Dyes, Department of Chemistry, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece
| | - Ioanna Koumentakou
- Laboratory of Chemistry and Technology of Polymers and Dyes, Department of Chemistry, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece
| | - Georgia Michailidou
- Laboratory of Chemistry and Technology of Polymers and Dyes, Department of Chemistry, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece
| | - Michiel Jan Noordam
- Laboratory of Chemistry and Technology of Polymers and Dyes, Department of Chemistry, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece
| | - Dimitrios N Bikiaris
- Laboratory of Chemistry and Technology of Polymers and Dyes, Department of Chemistry, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece
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16
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Shestovskaya MV, Bozhkova SA, Sopova JV, Khotin MG, Bozhokin MS. Methods of Modification of Mesenchymal Stem Cells and Conditions of Their Culturing for Hyaline Cartilage Tissue Engineering. Biomedicines 2021; 9:biomedicines9111666. [PMID: 34829895 PMCID: PMC8615732 DOI: 10.3390/biomedicines9111666] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 11/04/2021] [Accepted: 11/05/2021] [Indexed: 12/24/2022] Open
Abstract
The use of mesenchymal stromal cells (MSCs) for tissue engineering of hyaline cartilage is a topical area of regenerative medicine that has already entered clinical practice. The key stage of this procedure is to create conditions for chondrogenic differentiation of MSCs, increase the synthesis of hyaline cartilage extracellular matrix proteins by these cells and activate their proliferation. The first such works consisted in the indirect modification of cells, namely, in changing the conditions in which they are located, including microfracturing of the subchondral bone and the use of 3D biodegradable scaffolds. The most effective methods for modifying the cell culture of MSCs are protein and physical, which have already been partially introduced into clinical practice. Genetic methods for modifying MSCs, despite their effectiveness, have significant limitations. Techniques have not yet been developed that allow studying the effectiveness of their application even in limited groups of patients. The use of MSC modification methods allows precise regulation of cell culture proliferation, and in combination with the use of a 3D biodegradable scaffold, it allows obtaining a hyaline-like regenerate in the damaged area. This review is devoted to the consideration and comparison of various methods used to modify the cell culture of MSCs for their use in regenerative medicine of cartilage tissue.
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Affiliation(s)
- Maria V. Shestovskaya
- Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky Ave. 4, 194064 St. Petersburg, Russia; (M.V.S.); (J.V.S.); (M.G.K.)
| | - Svetlana A. Bozhkova
- Vreden National Medical Research Center of Traumatology and Orthopedics, Academica Baykova Str., 8, 195427 St. Petersburg, Russia;
| | - Julia V. Sopova
- Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky Ave. 4, 194064 St. Petersburg, Russia; (M.V.S.); (J.V.S.); (M.G.K.)
- Center of Transgenesis and Genome Editing, St. Petersburg State University, Universitetskaja Emb., 7/9, 199034 St. Petersburg, Russia
| | - Mikhail G. Khotin
- Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky Ave. 4, 194064 St. Petersburg, Russia; (M.V.S.); (J.V.S.); (M.G.K.)
| | - Mikhail S. Bozhokin
- Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky Ave. 4, 194064 St. Petersburg, Russia; (M.V.S.); (J.V.S.); (M.G.K.)
- Vreden National Medical Research Center of Traumatology and Orthopedics, Academica Baykova Str., 8, 195427 St. Petersburg, Russia;
- Correspondence:
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17
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Horbert V, Xin L, Föhr P, Huber R, Burgkart RH, Kinne RW. In Vitro Cartilage Regeneration with a Three-Dimensional Polyglycolic Acid (PGA) Implant in a Bovine Cartilage Punch Model. Int J Mol Sci 2021; 22:11769. [PMID: 34769199 PMCID: PMC8583898 DOI: 10.3390/ijms222111769] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 10/25/2021] [Accepted: 10/26/2021] [Indexed: 12/19/2022] Open
Abstract
Resorbable polyglycolic acid (PGA) chondrocyte grafts are clinically established for human articular cartilage defects. Long-term implant performance was addressed in a standardized in vitro model. PGA implants (+/- bovine chondrocytes) were placed inside cartilage rings punched out of bovine femoral trochleas (outer Ø 6 mm; inner defect Ø 2 mm) and cultured for 84 days (12 weeks). Cartilage/PGA hybrids were subsequently analyzed by histology (hematoxylin/eosin; safranin O), immunohistochemistry (aggrecan, collagens 1 and 2), protein assays, quantitative real-time polymerase chain reactions, and implant push-out force measurements. Cartilage/PGA hybrids remained vital with intact matrix until 12 weeks, limited loss of proteoglycans from "host" cartilage or cartilage-PGA interface, and progressively diminishing release of proteoglycans into the supernatant. By contrast, the collagen 2 content in cartilage and cartilage-PGA interface remained approximately constant during culture (with only little collagen 1). Both implants (+/- cells) displayed implant colonization and progressively increased aggrecan and collagen 2 mRNA, but significantly decreased push-out forces over time. Cell-loaded PGA showed significantly accelerated cell colonization and significantly extended deposition of aggrecan. Augmented chondrogenic differentiation in PGA and cartilage/PGA-interface for up to 84 days suggests initial cartilage regeneration. Due to the PGA resorbability, however, the model exhibits limitations in assessing the "lateral implant bonding".
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Affiliation(s)
- Victoria Horbert
- Experimental Rheumatology Unit, Orthopedic Professorship, Jena University Hospital, Waldkliniken Eisenberg GmbH, 07607 Eisenberg, Germany; (V.H.); (L.X.)
| | - Long Xin
- Experimental Rheumatology Unit, Orthopedic Professorship, Jena University Hospital, Waldkliniken Eisenberg GmbH, 07607 Eisenberg, Germany; (V.H.); (L.X.)
- Department of Orthopedics, Tongde Hospital of Zhejiang Province, Hangzhou 310012, China
| | - Peter Föhr
- Biomechanics Laboratory, Chair of Orthopedics and Sport Orthopedics, Technische Universität München, 81675 Munich, Germany; (P.F.); (R.H.B.)
| | - René Huber
- Institute of Clinical Chemistry, Hannover Medical School, 30625 Hannover, Germany;
| | - Rainer H. Burgkart
- Biomechanics Laboratory, Chair of Orthopedics and Sport Orthopedics, Technische Universität München, 81675 Munich, Germany; (P.F.); (R.H.B.)
| | - Raimund W. Kinne
- Experimental Rheumatology Unit, Orthopedic Professorship, Jena University Hospital, Waldkliniken Eisenberg GmbH, 07607 Eisenberg, Germany; (V.H.); (L.X.)
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18
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Dieterle MP, Husari A, Rolauffs B, Steinberg T, Tomakidi P. Integrins, cadherins and channels in cartilage mechanotransduction: perspectives for future regeneration strategies. Expert Rev Mol Med 2021; 23:e14. [PMID: 34702419 PMCID: PMC8724267 DOI: 10.1017/erm.2021.16] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Revised: 09/16/2021] [Accepted: 09/20/2021] [Indexed: 02/07/2023]
Abstract
Articular cartilage consists of hyaline cartilage, is a major constituent of the human musculoskeletal system and has critical functions in frictionless joint movement and articular homoeostasis. Osteoarthritis (OA) is an inflammatory disease of articular cartilage, which promotes joint degeneration. Although it affects millions of people, there are no satisfying therapies that address this disease at the molecular level. Therefore, tissue regeneration approaches aim at modifying chondrocyte biology to mitigate the consequences of OA. This requires appropriate biochemical and biophysical stimulation of cells. Regarding the latter, mechanotransduction of chondrocytes and their precursor cells has become increasingly important over the last few decades. Mechanotransduction is the transformation of external biophysical stimuli into intracellular biochemical signals, involving sensor molecules at the cell surface and intracellular signalling molecules, so-called mechano-sensors and -transducers. These signalling events determine cell behaviour. Mechanotransducing ion channels and gap junctions additionally govern chondrocyte physiology. It is of great scientific and medical interest to induce a specific cell behaviour by controlling these mechanotransduction pathways and to translate this knowledge into regenerative clinical therapies. This review therefore focuses on the mechanotransduction properties of integrins, cadherins and ion channels in cartilaginous tissues to provide perspectives for cartilage regeneration.
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Affiliation(s)
- Martin Philipp Dieterle
- Division of Oral Biotechnology, Center for Dental Medicine, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106Freiburg, Germany
| | - Ayman Husari
- Division of Oral Biotechnology, Center for Dental Medicine, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106Freiburg, Germany
- Department of Orthodontics, Center for Dental Medicine, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106Freiburg, Germany
| | - Bernd Rolauffs
- Department of Orthopedics and Trauma Surgery, G.E.R.N. Research Center for Tissue Replacement, Regeneration & Neogenesis, Medical Center – Albert-Ludwigs-University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, 79085Freiburg im Breisgau, Germany
| | - Thorsten Steinberg
- Division of Oral Biotechnology, Center for Dental Medicine, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106Freiburg, Germany
| | - Pascal Tomakidi
- Division of Oral Biotechnology, Center for Dental Medicine, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106Freiburg, Germany
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Qiao K, Chen Q, Cao Y, Li J, Xu G, Liu J, Cui X, Tian K, Zhang W. Diagnostic and Therapeutic Role of Extracellular Vesicles in Articular Cartilage Lesions and Degenerative Joint Diseases. Front Bioeng Biotechnol 2021; 9:698614. [PMID: 34422779 PMCID: PMC8371972 DOI: 10.3389/fbioe.2021.698614] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Accepted: 06/28/2021] [Indexed: 01/15/2023] Open
Abstract
Two leading contributors to the global disability are cartilage lesions and degenerative joint diseases, which are characterized by the progressive cartilage destruction. Current clinical treatments often fail due to variable outcomes and an unsatisfactory long-term repair. Cell-based therapies were once considered as an effective solution because of their anti-inflammatory and immunosuppression characteristics as well as their differentiation capacity to regenerate the damaged tissue. However, stem cell-based therapies have inherent limitations, such as a high tumorigenicity risk, a low retention, and an engraftment rate, as well as strict regulatory requirements, which result in an underwhelming therapeutic effect. Therefore, the non-stem cell-based therapy has gained its popularity in recent years. Extracellular vesicles (EVs), in particular, like the paracrine factors secreted by stem cells, have been proven to play a role in mediating the biological functions of target cells, and can achieve the therapeutic effect similar to stem cells in cartilage tissue engineering. Therefore, a comprehensive review of the therapeutic role of EVs in cartilage lesions and degenerative joint diseases can be discussed both in terms of time and favorability. In this review, we summarized the physiological environment of a joint and its pathological alteration after trauma and consequent changes in EVs, which are lacking in the current literature studies. In addition, we covered the potential working mechanism of EVs in the repair of the cartilage and the joint and also discussed the potential therapeutic applications of EVs in future clinical use.
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Affiliation(s)
- Kai Qiao
- First Affiliated Hospital, Dalian Medical University, Dalian, China
| | - Qi Chen
- First Affiliated Hospital, Dalian Medical University, Dalian, China
| | - Yiguo Cao
- First Affiliated Hospital, Dalian Medical University, Dalian, China
| | - Jie Li
- First Affiliated Hospital, Dalian Medical University, Dalian, China
| | - Gang Xu
- First Affiliated Hospital, Dalian Medical University, Dalian, China
| | - Jiaqing Liu
- Qingdao University of Science and Technology, Qingdao, China
| | - Xiaolin Cui
- First Affiliated Hospital, Dalian Medical University, Dalian, China
- Department of Orthopaedic Surgery and Musculoskeletal Medicine, University of Otago, Christchurch, New Zealand
| | - Kang Tian
- First Affiliated Hospital, Dalian Medical University, Dalian, China
- Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
| | - Weiguo Zhang
- First Affiliated Hospital, Dalian Medical University, Dalian, China
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20
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[Cartilage repair procedures for early osteoarthritis]. DER ORTHOPADE 2021; 50:356-365. [PMID: 33844031 DOI: 10.1007/s00132-021-04099-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 03/10/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND Commonly used cartilage repair procedures have been established for focal cartilage lesions; however, degenerative lesions with accompanying changes of other intraarticular structures are much more common in clinical practice. This stage, in which classic radiological signs of osteoarthritis are absent, is called early osteoarthritis and is characterized by impaired joint homeostasis with biomechanical and biochemical changes that can have a negative effect on regenerative cartilage therapy procedures. INDICATION Cartilage repair procedures are indicated for symptomatic focal early osteoarthritis, defined as cartilage degeneration ICRS grades I or II around a focal cartilage defect ICRS grades III or IV. In more advanced osteoarthritis with significant narrowing of the joint space, cartilage repair procedures are generally contraindicated. THERAPY The most studied cartilage repair procedure for early osteoarthritis is autologous chondrocyte implantation, which has shown acceptable results in case series, although higher failure rates are to be expected compared to focal, traumatic cartilage lesions. The use of bone marrow-stimulating techniques seems to be limited in early osteoarthritis and should only be used in cases of lesion < 2 cm2 and very little surrounding cartilage degeneration. Concomitant surgical procedures, especially unloading osteotomies, are very important.
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21
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Zak L, Kleiner A, Albrecht C, Tichy B, Aldrian S. Third-Generation Autologous Chondrocyte Implantation at the Knee Joint Using the Igor Scaffold: A Case Series With 2-Year Follow-up. Orthop J Sports Med 2021; 9:2325967120969237. [PMID: 33553440 PMCID: PMC7841690 DOI: 10.1177/2325967120969237] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Accepted: 06/30/2020] [Indexed: 12/18/2022] Open
Abstract
Background: For large, locally restricted cartilage defects in young patients, third-generation matrix-supported autologous chondrocyte implantation (ACI) with a variety of scaffolds has shown good mid- to long-term results. Purpose/Hypothesis: This study aimed to monitor the clinical and radiological outcomes of patients who received ACI at the knee joint using the Igor scaffold (IGOR–Institute for Tissue and Organ Reconstruction) at 2-year follow-up. Our hypothesis was that there would be improvements in postoperative subjective scores and cartilage repair tissue quality. Study Design: Case series; Level of evidence, 4. Methods: A total of 21 patients (12 male and 9 female) were available for 2-year follow-up after third-generation ACI using the Igor scaffold. All were clinically assessed using the Knee injury and Osteoarthritis Outcome Score (KOOS), Tegner Activity Scale, Brittberg score, International Knee Documentation Committee (IKDC) Subjective Knee Form, Noyes Sports Activity Rating Scale, and visual analog scale for pain. For morphological evaluation, the magnetic resonance observation of cartilage repair tissue (MOCART) and MOCART 2.0 scores were calculated using 3-T magnetic resonance imaging performed at 3, 6, 12, and 24 months postoperatively. Results were compared between baseline and 24 months postoperatively. Results: After 2 years, the clinical and radiological scores showed good to excellent results in the majority of patients. On the IKDC, 10 patients were graded as excellent, 4 as good, 5 as fair, and 2 as severe; on the KOOS, 7 patients were graded as excellent, 8 as good, 4 as fair, and 2 as severe. From baseline to latest follow-up, visual analog scale pain scores decreased from 5.6 ± 3.2 (mean ± SD) to 1.5 ± 2; KOOS results increased from 51 ± 20.7 to 75.2 ± 15.4; and the Tegner score improved from 2.2 ± 1.8 to 4.3 ± 1.3. The MOCART and MOCART 2.0 scores were comparable at 2-year follow-up, with mean values of 74 ± 10 and 78 ± 13, respectively. Satisfactory filling and integration were found in 90.5%. Overall, 16 of 21 patients (76.1%) were satisfied with the surgery and would undergo the procedure again. Conclusion: Third-generation ACI using the Igor scaffold showed improvements in clinical and radiological results that were comparable with other scaffolds for patients with large traumatic or degenerative cartilage defects. Patients reported a decrease in pain and an increase in activity, with the majority reporting good results.
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Affiliation(s)
- Lukas Zak
- Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Vienna, Austria
- Lukas Zak, MD, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria ()
| | - Anne Kleiner
- Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Vienna, Austria
| | - Christian Albrecht
- First Orthopaedic Department, Orthopaedic Hospital Speising, Vienna, Austria
| | - Brigitte Tichy
- Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Vienna, Austria
| | - Silke Aldrian
- Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Vienna, Austria
- Austrian Cluster of Tissue Regeneration, Vienna, Austria
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Evolution of hydrogels for cartilage tissue engineering of the knee: A systematic review and meta-analysis of clinical studies. Joint Bone Spine 2020; 88:105096. [PMID: 33157230 DOI: 10.1016/j.jbspin.2020.105096] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 10/06/2020] [Indexed: 01/03/2023]
Abstract
INTRODUCTION In recent years, studies have boosted our knowledge about the biology and disorders of articular cartilage. In this regard, the design of hydrogel-based scaffolds has advanced to improve cartilage repair. However, the efficacy of knee cartilage repair using hydrogels remains unclear. The aim of systematic review and meta-analysis was to scrutinize the efficiency of hydrogel-based therapy in correcting cartilage defects of knee (femoral condyle, patella, tibia plateau and trochlea). METHODS The search was conducted in PubMed to gather articles published from 2004/1/1 to 2019/10/01, addressing the effects of implant of hydrogel on knee joint cartilage regeneration. The Cochrane Collaboration's tool for estimating the risk of bias was applied to check the quality of articles. The clinical data for meta-analysis was recorded using the visual analog scale (VAS), Lysholm score, WOMAC, and IKDC. The guidelines of Cochrane Handbook for Systematic Reviews of Interventions were utilized to conduct the review and meta-analysis in the RevMan 5.3 software. RESULTS The search resulted in 50 clinical trials that included 2846 patients, 986 of whom received cell-based hydrogel implants while 1860 patients used hydrogel without cell. There were significant differences comparing the pain scores based on the VAS (MD: -2.97; 95% CI: -3.15 to -2.79, P<0.00001) and WOMAC (MD: -25.22; 95% CI: -31.22 to -19.22, P<0.00001) between pre- and post-treatment with hydrogels. Furthermore, there were significant improvements in the functional scores based on the IKDC total score (MD: 30.67; P<0.00001) and the Lysholm knee scale (MD: 29.26; 95% CI: 26.74 to 31.78, P<0.00001). According to the Lysholm and IKDC score and after cumulative functional analysis, there was a significant improvement in this parameter (MD: 29.25; 95% CI: 27.26 to 31.25, P<0.00001). CONCLUSIONS This meta-analysis indicated clinically and statistically significant improvements in the pain score (VAS and WOMAC) and the functional score (IKDC and Lysholm) after the administration of hydrogel compared to pretreatment status. So, the current evidence shows the efficiency of hydrogel-based therapy in correcting and repairing knee cartilage defects.
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23
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Rahmani Del Bakhshayesh A, Babaie S, Tayefi Nasrabadi H, Asadi N, Akbarzadeh A, Abedelahi A. An overview of various treatment strategies, especially tissue engineering for damaged articular cartilage. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2020; 48:1089-1104. [DOI: 10.1080/21691401.2020.1809439] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Azizeh Rahmani Del Bakhshayesh
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Tissue Engineering, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Soraya Babaie
- Department of Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hamid Tayefi Nasrabadi
- Department of Tissue Engineering, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Nahideh Asadi
- Department of Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Abolfazl Akbarzadeh
- Department of Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ali Abedelahi
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Tissue Engineering, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
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24
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Xue J, Pisignano D, Xia Y. Maneuvering the Migration and Differentiation of Stem Cells with Electrospun Nanofibers. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2020; 7:2000735. [PMID: 32775158 PMCID: PMC7404157 DOI: 10.1002/advs.202000735] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 04/30/2020] [Indexed: 05/21/2023]
Abstract
Electrospun nanofibers have been extensively explored as a class of scaffolding materials for tissue regeneration, because of their unique capability to mimic some features and functions of the extracellular matrix, including the fibrous morphology and mechanical properties, and to a certain extent the chemical/biological cues. This work reviews recent progress in applying electrospun nanofibers to direct the migration of stem cells and control their differentiation into specific phenotypes. First, the physicochemical properties that make electrospun nanofibers well-suited as a supporting material to expand stem cells by controlling their migration and differentiation are introduced. Then various systems are analyzed in conjunction with mesenchymal, neuronal, and embryonic stem cells, as well as induced pluripotent stem cells. Finally, some perspectives on the challenges and future opportunities in combining electrospun nanofibers with stem cells are offered to address clinical issues.
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Affiliation(s)
- Jiajia Xue
- The Wallace H. Coulter Department of Biomedical EngineeringGeorgia Institute of Technology and Emory UniversityAtlantaGA30332USA
| | - Dario Pisignano
- Dipartimento di FisicaUniversità di PisaLargo B. Pontecorvo 3PisaI‐56127Italy
- NESTIstituto Nanoscienze‐CNRPiazza S. Silvestro 12PisaI‐56127Italy
| | - Younan Xia
- The Wallace H. Coulter Department of Biomedical EngineeringGeorgia Institute of Technology and Emory UniversityAtlantaGA30332USA
- School of Chemistry and BiochemistrySchool of Chemical and Biomolecular EngineeringGeorgia Institute of TechnologyAtlantaGA30332USA
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25
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Niethammer TR, Altmann D, Holzgruber M, Gülecyüz MF, Notohamiprodjo S, Baur-Melnyk A, Müller PE. Patient-Reported and Magnetic Resonance Imaging Outcomes of Third-Generation Autologous Chondrocyte Implantation After 10 Years. Arthroscopy 2020; 36:1928-1938. [PMID: 32200064 DOI: 10.1016/j.arthro.2020.03.009] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2019] [Revised: 02/27/2020] [Accepted: 03/01/2020] [Indexed: 02/02/2023]
Abstract
PURPOSE To evaluate the long-term clinical and radiologic outcomes of third-generation autologous chondrocyte implantation (ACI) for the treatment of focal cartilage defects of the knee. METHODS Data capture was carried out between 2004 and 2018. Included were patients with cartilage defects of the knee joint with an International Cartilage Repair Society grade of III or higher treated with third-generation ACI who had a minimum follow-up period of 10 years. International Knee Documentation Committee scores and assessment of pain at rest and on movement using visual analog scale scores were captured preoperatively and at 6 months postoperatively, as well as annually thereafter. In addition, we performed magnetic resonance imaging examinations in 13 cases after 10 years. The MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score was used to evaluate the ACI cartilage. RESULTS A total of 54 patients met the inclusion criteria. Of these, 30 reached the 10-year follow-up point and were included in this assessment. At 10 years postoperatively, all clinical outcome parameters showed a statistically significant improvement compared with the preoperative situation, with a responder rate of 70%. The average MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score after 10 years was 59.2 points (range, 20-100 points), and over 60% of the evaluated patients showed good integration of the implant at 10 years postoperatively. CONCLUSIONS The clinical and radiologic findings of this study show that third-generation ACI is a suitable and effective option in the treatment of full-thickness cartilage defects of the knee. At 10 years after surgery, third-generation ACI shows stable results and leads to significant improvement in all clinical outcome parameters. Despite these results, revision surgery after third-generation ACI is common and was needed in 23% of patients in this study. LEVEL OF EVIDENCE Level IV, therapeutic case series.
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Affiliation(s)
- Thomas R Niethammer
- Department of Orthopaedics, Physical Medicine and Rehabilitation, University Hospital, LMU Munich, Munich, Germany; Department of Radiology, University Hospital, LMU Munich, Munich, Germany.
| | - Daniel Altmann
- Department of Orthopaedics, Physical Medicine and Rehabilitation, University Hospital, LMU Munich, Munich, Germany; Department of Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Martin Holzgruber
- Department of Orthopaedics, Physical Medicine and Rehabilitation, University Hospital, LMU Munich, Munich, Germany; Department of Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Mehmet F Gülecyüz
- Department of Orthopaedics, Physical Medicine and Rehabilitation, University Hospital, LMU Munich, Munich, Germany; Department of Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Susan Notohamiprodjo
- Department of Orthopaedics, Physical Medicine and Rehabilitation, University Hospital, LMU Munich, Munich, Germany; Department of Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Andrea Baur-Melnyk
- Department of Orthopaedics, Physical Medicine and Rehabilitation, University Hospital, LMU Munich, Munich, Germany; Department of Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Peter E Müller
- Department of Orthopaedics, Physical Medicine and Rehabilitation, University Hospital, LMU Munich, Munich, Germany; Department of Radiology, University Hospital, LMU Munich, Munich, Germany
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26
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Clinical Application Status of Articular Cartilage Regeneration Techniques: Tissue-Engineered Cartilage Brings New Hope. Stem Cells Int 2020; 2020:5690252. [PMID: 32676118 PMCID: PMC7345961 DOI: 10.1155/2020/5690252] [Citation(s) in RCA: 65] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2019] [Revised: 05/22/2020] [Accepted: 05/28/2020] [Indexed: 12/16/2022] Open
Abstract
Hyaline articular cartilage lacks blood vessels, lymphatics, and nerves and is characterised by limited self-repair ability following injury. Traditional techniques of articular cartilage repair and regeneration all have certain limitations. The development of tissue engineering technology has brought hope to the regeneration of articular cartilage. The strategies of tissue-engineered articular cartilage can be divided into three types: “cell-scaffold construct,” cell-free, and scaffold-free. In “cell-scaffold construct” strategies, seed cells can be autologous chondrocytes or stem. Among them, some commercial products with autologous chondrocytes as seed cells, such as BioSeed®-C and CaReS®, have been put on the market and some products are undergoing clinical trials, such as NOVOCART® 3D. The stem cells are mainly pluripotent stem cells and mesenchymal stem cells from different sources. Cell-free strategies that indirectly utilize the repair and regeneration potential of stem cells have also been used in clinical settings, such as TruFit and MaioRegen. Finally, the scaffold-free strategy is also a new development direction, and the short-term repair results of related products, such as NOVOCART® 3D, are encouraging. In this paper, the commonly used techniques of articular cartilage regeneration in surgery are reviewed. By studying different strategies and different seed cells, the clinical application status of tissue-engineered articular cartilage is described in detail.
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27
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Eftekhari A, Maleki Dizaj S, Sharifi S, Salatin S, Rahbar Saadat Y, Zununi Vahed S, Samiei M, Ardalan M, Rameshrad M, Ahmadian E, Cucchiarini M. The Use of Nanomaterials in Tissue Engineering for Cartilage Regeneration; Current Approaches and Future Perspectives. Int J Mol Sci 2020; 21:E536. [PMID: 31947685 PMCID: PMC7014227 DOI: 10.3390/ijms21020536] [Citation(s) in RCA: 72] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2019] [Revised: 01/06/2020] [Accepted: 01/08/2020] [Indexed: 01/16/2023] Open
Abstract
The repair and regeneration of articular cartilage represent important challenges for orthopedic investigators and surgeons worldwide due to its avascular, aneural structure, cellular arrangement, and dense extracellular structure. Although abundant efforts have been paid to provide tissue-engineered grafts, the use of therapeutically cell-based options for repairing cartilage remains unsolved in the clinic. Merging a clinical perspective with recent progress in nanotechnology can be helpful for developing efficient cartilage replacements. Nanomaterials, < 100 nm structural elements, can control different properties of materials by collecting them at nanometric sizes. The integration of nanomaterials holds promise in developing scaffolds that better simulate the extracellular matrix (ECM) environment of cartilage to enhance the interaction of scaffold with the cells and improve the functionality of the engineered-tissue construct. This technology not only can be used for the healing of focal defects but can also be used for extensive osteoarthritic degenerative alterations in the joint. In this review paper, we will emphasize the recent investigations of articular cartilage repair/regeneration via biomaterials. Also, the application of novel technologies and materials is discussed.
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Affiliation(s)
- Aziz Eftekhari
- Pharmacology and Toxicology Department, Maragheh University of Medical Sciences, 5515878151 Maragheh, Iran
| | - Solmaz Maleki Dizaj
- Dental and Periodontal Research Center, Tabriz University of Medical Sciences, 5166614756 Tabriz, Iran
| | - Simin Sharifi
- Dental and Periodontal Research Center, Tabriz University of Medical Sciences, 5166614756 Tabriz, Iran
| | - Sara Salatin
- Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tabriz University of Medical Science, 5166614756 Tabriz, Iran
| | - Yalda Rahbar Saadat
- Nutrition Research Center, Tabriz University of Medical Sciences, 5166614756 Tabriz, Iran
| | - Sepideh Zununi Vahed
- Kidney Research Center, Tabriz University of Medical Sciences, 5166614756 Tabriz, Iran
| | - Mohammad Samiei
- Faculty of Dentistry, Tabriz University of Medical Sciences, 5166614756 Tabriz, Iran
| | - Mohammadreza Ardalan
- Kidney Research Center, Tabriz University of Medical Sciences, 5166614756 Tabriz, Iran
| | - Maryam Rameshrad
- Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, 9414975516 Bojnurd, Iran
| | - Elham Ahmadian
- Kidney Research Center, Tabriz University of Medical Sciences, 5166614756 Tabriz, Iran
- Student Research Committee, Tabriz University of Medical Sciences, 5166614756 Tabriz, Iran
| | - Magali Cucchiarini
- Center of Experimental Orthopaedics, Saarland University Medical Center, D-66421 Homburg/Saar, Germany
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Ebert JR, Smith A, Janes GC, Wood DJ. Association Between Isokinetic Knee Strength and Perceived Function and Patient Satisfaction With Sports and Recreational Ability After Matrix-Induced Autologous Chondrocyte Implantation. Orthop J Sports Med 2019; 7:2325967119885873. [PMID: 31903396 PMCID: PMC6923694 DOI: 10.1177/2325967119885873] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
Background: Returning to a sound level of activity after matrix-induced autologous
chondrocyte implantation (MACI) is important to patients. Evaluating the
patient’s level of satisfaction with his or her sports and recreational
ability is critical. Purpose: To investigate (1) satisfaction with sports and recreational ability after
MACI and (2) the role that knee strength plays in self-reported knee
function and satisfaction. Study Design: Case-control study; Level of evidence, 3. Methods: Isokinetic knee strength was assessed in 97 patients at 1, 2, and 5 years
after MACI to calculate hamstrings-quadriceps ratios and peak knee extensor
and flexor torque limb symmetry indices (LSIs). The Sports and Recreation
subscale of the Knee injury and Osteoarthritis Outcome Score (KOOS
Sports/Rec) was completed. A satisfaction scale was used to evaluate how
satisfied the patients were with their ability to return to recreational
activities and their ability to participate in sport. Associations between
knee strength LSI, KOOS Sports/Rec, and satisfaction with recreational and
sporting activities were assessed through use of multivariable linear and
logistic regression, with adjustment for confounders. Mediation analysis was
conducted to assess the extent to which self-reported knee function mediated
associations between strength LSI and satisfaction. Results: Satisfaction with the ability to return to recreational activities was
achieved in 82.4%, 85.6%, and 85.9% of patients at 1, 2, and 5 years,
respectively, and satisfaction with sports participation was achieved in
55.7%, 73.2%, and 68.5% of patients at 1, 2, and 5 years, respectively. Knee
extension torque LSIs were associated with KOOS Sports/Rec after adjustment
for confounders over 1, 2, and 5 years (5-year regression coefficient, 6.0
points; 95% CI, 1.4-10.7; P = .012). KOOS Sports/Rec was
associated with the likelihood of being satisfied at all time points
(recreation: 5-year adjusted odds ratio [OR], 2.26; 95% CI, 1.48-3.46;
P < .001; and sports: 5-year adjusted OR, 1.98; 95%
CI, 1.47-2.68; P < .001). In a multivariable mediation
model, the knee extension torque LSI was associated with satisfaction
directly (standardized coefficient, 0.16; 95% CI, 0.03-0.28;
P = .017) and indirectly via KOOS Sports/Rec
(standardized coefficient, 0.19; 95% CI, 0.01-0.38; P =
.027), the latter representing 55% of the total association of knee
extension torque LSI with satisfaction. Conclusion: Knee extensor symmetry was associated with satisfaction in recreational and
sporting ability, both directly and indirectly, via self-reported sports and
recreation–related knee function. Restoring strength deficits after MACI is
important for achieving optimal outcomes.
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Affiliation(s)
- Jay R Ebert
- School of Human Sciences (Exercise and Sport Science), University of Western Australia, Crawley, Perth, Western Australia, Australia
| | - Anne Smith
- School of Physiotherapy and Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, Western Australia, Australia
| | - Gregory C Janes
- Perth Orthopaedic and Sports Medicine Centre, West Perth, Western Australia, Australia
| | - David J Wood
- School of Surgery (Orthopaedics), University of Western Australia, Crawley, Perth, Western Australia, Australia
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Kwon H, Brown WE, Lee CA, Wang D, Paschos N, Hu JC, Athanasiou KA. Surgical and tissue engineering strategies for articular cartilage and meniscus repair. Nat Rev Rheumatol 2019; 15:550-570. [PMID: 31296933 PMCID: PMC7192556 DOI: 10.1038/s41584-019-0255-1] [Citation(s) in RCA: 413] [Impact Index Per Article: 68.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/07/2019] [Indexed: 12/30/2022]
Abstract
Injuries to articular cartilage and menisci can lead to cartilage degeneration that ultimately results in arthritis. Different forms of arthritis affect ~50 million people in the USA alone, and it is therefore crucial to identify methods that will halt or slow the progression to arthritis, starting with the initiating events of cartilage and meniscus defects. The surgical approaches in current use have a limited capacity for tissue regeneration and yield only short-term relief of symptoms. Tissue engineering approaches are emerging as alternatives to current surgical methods for cartilage and meniscus repair. Several cell-based and tissue-engineered products are currently in clinical trials for cartilage lesions and meniscal tears, opening new avenues for cartilage and meniscus regeneration. This Review provides a summary of surgical techniques, including tissue-engineered products, that are currently in clinical use, as well as a discussion of state-of-the-art tissue engineering strategies and technologies that are being developed for use in articular cartilage and meniscus repair and regeneration. The obstacles to clinical translation of these strategies are also included to inform the development of innovative tissue engineering approaches.
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Affiliation(s)
- Heenam Kwon
- Department of Biomedical Engineering, University of California Irvine, Irvine, CA, USA
| | - Wendy E Brown
- Department of Biomedical Engineering, University of California Irvine, Irvine, CA, USA
| | - Cassandra A Lee
- Department of Orthopaedic Surgery, University of California Davis Medical Center, Sacramento, CA, USA
| | - Dean Wang
- Department of Orthopaedic Surgery, University of California Irvine Medical Center, Orange, CA, USA
| | - Nikolaos Paschos
- Division of Sports Medicine, Department of Orthopaedic Surgery, New England Baptist Hospital, Tufts University School of Medicine, Boston, MA, USA
| | - Jerry C Hu
- Department of Biomedical Engineering, University of California Irvine, Irvine, CA, USA
| | - Kyriacos A Athanasiou
- Department of Biomedical Engineering, University of California Irvine, Irvine, CA, USA.
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Andriolo L, Reale D, Di Martino A, Zaffagnini S, Vannini F, Ferruzzi A, Filardo G. High Rate of Failure After Matrix-Assisted Autologous Chondrocyte Transplantation in Osteoarthritic Knees at 15 Years of Follow-up. Am J Sports Med 2019; 47:2116-2122. [PMID: 31211592 DOI: 10.1177/0363546519855029] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Chondral and osteochondral lesions in osteoarthritic knees of young patients remain challenging for orthopaedic surgeons, due to a combination of high functional demands and limited indications for joint replacement in this population. The possibility of extending the indication of cartilage regenerative procedures to these patients may allow the delay of metal resurfacing. PURPOSE To analyze the potential of a cartilage regenerative approach to provide clinical benefits in young patients with osteoarthritic knees, documenting outcomes in terms of clinical improvement as well as failures, in particular regarding knee replacement, at long-term follow-up. STUDY DESIGN Case series; Level of evidence, 4. METHODS A total of 41 patients (mean ± SD age, 43 ± 9 years) who had cartilage lesions (4 ± 2 cm2) in osteoarthritic knees (Kellgren-Lawrence grade 2 or 3) underwent matrix-assisted autologous chondrocyte transplantation (MACT) as a salvage procedure. Patients were evaluated with International Knee Documentation Committee (IKDC), EuroQol visual analog scale (EQ-VAS), and Tegner scores before surgery; at 1, 2, 5, and 9 years after surgery; and at a final follow-up at a mean of 15 years after surgery (range, 14-18 years). Failures were also recorded. RESULTS An improvement was observed in all scores after surgery, but a progressive worsening over time was noted. The mean ± SD IKDC score improved from 38.6 ± 16.2 to a maximum of 66.0 ± 18.6 at 2 years (P < .0005), with a subsequent deterioration until the final evaluation at 56.2 ± 21.7 (P = .024). A similar trend was confirmed by EQ-VAS scores. Tegner scores improved at all follow-up points but did not reach the preinjury level. Patients who underwent combined surgery obtained significantly lower results. Only 13 patients (32%) had an IKDC score higher than 70. During the follow-up period, 21 patients underwent reoperation (18 with knee replacement) and 3 more patients experienced clinical failure, for a total surgical and clinical failure rate of 59% at 15 years. CONCLUSION The use of cartilage regenerative surgical procedures, such as MACT, as salvage procedures for young, active patients affected by chondral and osteochondral lesions in osteoarthritic knees led to a limited improvement, with the majority of patients experiencing failure at long-term follow-up. Although a minor subpopulation experienced favorable and stable improvement, the use of MACT for such a challenging indication remains questionable until responding patients can be profiled.
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Affiliation(s)
- Luca Andriolo
- II Orthopaedic and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Davide Reale
- II Orthopaedic and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Alessandro Di Martino
- II Orthopaedic and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Stefano Zaffagnini
- II Orthopaedic and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Francesca Vannini
- I Orthopaedic and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Alberto Ferruzzi
- I Orthopaedic and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Giuseppe Filardo
- Applied and Translational Research Center, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
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Kreuz PC, Kalkreuth RH, Niemeyer P, Uhl M, Erggelet C. Long-Term Clinical and MRI Results of Matrix-Assisted Autologous Chondrocyte Implantation for Articular Cartilage Defects of the Knee. Cartilage 2019; 10:305-313. [PMID: 29429373 PMCID: PMC6585297 DOI: 10.1177/1947603518756463] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
OBJECTIVE To evaluate the long-term clinical and radiological outcome of matrix-assisted autologous chondrocyte implantation (mACI) for articular cartilage defects in the knee joint. DESIGN Clinical evaluation was assessed in 21 patients with full-thickness cartilage defects, International Cartilage Repair Society (ICRS) grade IV. Clinical scoring was performed preoperatively and 12 years after transplantation using the International Knee Documentation Committee (IKDC) score, the Lysholm score, the Knee injury and Osteoarthritis Outcome Score (KOOS), and the Noyes sports activity rating scale. Morphologic evaluation of the repair tissue was assessed by magnetic resonance imaging (MRI) in 14 patients using the Kreuz-Henderson score. RESULTS Clinical evaluation revealed significant improvement in the IKDC, the Lysholm, the KOOS, and the Noyes score. Morphological evaluation by MRI showed moderate to complete defect filling in 10 of 14 patients, demonstrating normal to nearly normal values in mean 74.29% of all assessed parameters. Significant correlation of the parameter cartilage signal and clinical outcome was found with the IKDC, Lysholm, and KOOS subscales ADL (activities of daily living) and QoL (quality of life). CONCLUSIONS The clinical and radiological outcomes 12 years after transplantation suggest the confirmation of the promising results of the mid-term follow-up. This study therefore provides first indications that the implantation of mACI might be a suitable option for long-term cartilage repair. Future controlled studies need to address the exact parameters influencing the long-term outcome of mACI.
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Affiliation(s)
- Peter Cornelius Kreuz
- Department of Orthopaedic Surgery, University Medical Center Rostock, Rostock, Germany
| | - Richard Horst Kalkreuth
- Department of Orthopedic Surgery and Traumatology, Freiburg University Hospital, Freiburg, Germany,Richard Horst Kalkreuth, MD, Department of Orthopedic Surgery and Traumatology, Freiburg University Hospital, Hugstetter Str. 55, 79106 Freiburg, Germany.
| | - Philipp Niemeyer
- Department of Orthopedic Surgery and Traumatology, Freiburg University Hospital, Freiburg, Germany
| | - Markus Uhl
- Department of Radiology, RKK-Klinikum Freiburg, Freiburg, Germany
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Abstract
Tissue engineering (TE) and regenerative medicine are progressively developed areas due to many novel tissue replacements and implementation strategies. Increasing knowledge involving the fabrication of biomaterials with advanced physicochemical and biological characteristics, successful isolation and preparation of stem cells, incorporation of growth and differentiation factors, and biomimetic environments gives us a unique opportunity to develop various types of scaffolds for TE. The current strategies for soft tissue reconstitution or regeneration highlight the importance of novel regenerative therapies in cases of significant soft tissue loss and in cases of congenital defects, disease, trauma and ageing. Various types of biomaterials and scaffolds have been tested for soft tissue regeneration. The synthetic types of materials have gained great attention due to high versatility, tunability and easy functionalization for better biocompatibility. This article reviews the current materials that are usually the most used for the fabrication of scaffolds for soft TE; in addition, the types of scaffolds together with examples of their applications for the regenerative purposes of soft tissue, as well as their major physicochemical characteristics regarding the increased applicability of these materials in medicine, are reviewed.
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Affiliation(s)
- O Janoušková
- Department of Biological Models, Institute of Macromolecular Chemistry of the Czech Academy of Sciences, Prague 6, Czech Republic.
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Graceffa V, Vinatier C, Guicheux J, Stoddart M, Alini M, Zeugolis DI. Chasing Chimeras - The elusive stable chondrogenic phenotype. Biomaterials 2018; 192:199-225. [PMID: 30453216 DOI: 10.1016/j.biomaterials.2018.11.014] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Revised: 11/02/2018] [Accepted: 11/09/2018] [Indexed: 12/27/2022]
Abstract
The choice of the best-suited cell population for the regeneration of damaged or diseased cartilage depends on the effectiveness of culture conditions (e.g. media supplements, three-dimensional scaffolds, mechanical stimulation, oxygen tension, co-culture systems) to induce stable chondrogenic phenotype. Herein, advances and shortfalls in in vitro, preclinical and clinical setting of various in vitro microenvironment modulators on maintaining chondrocyte phenotype or directing stem cells towards chondrogenic lineage are critically discussed. Chondrocytes possess low isolation efficiency, limited proliferative potential and rapid phenotypic drift in culture. Mesenchymal stem cells are relatively readily available, possess high proliferation potential, exhibit great chondrogenic differentiation capacity, but they tend to acquire a hypertrophic phenotype when exposed to chondrogenic stimuli. Embryonic and induced pluripotent stem cells, despite their promising in vitro and preclinical data, are still under-investigated. Although a stable chondrogenic phenotype remains elusive, recent advances in in vitro microenvironment modulators are likely to develop clinically- and commercially-relevant therapies in the years to come.
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Affiliation(s)
- Valeria Graceffa
- Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, National University of Ireland Galway (NUI Galway), Galway, Ireland
| | - Claire Vinatier
- INSERMU1229, Regenerative Medicine and Skeleton (RMeS), University of Nantes, UFR Odontologie & CHU Nantes, PHU 4 OTONN, 44042 Nantes, France
| | - Jerome Guicheux
- INSERMU1229, Regenerative Medicine and Skeleton (RMeS), University of Nantes, UFR Odontologie & CHU Nantes, PHU 4 OTONN, 44042 Nantes, France
| | - Martin Stoddart
- AO Research Institute, Clavadelerstrasse 8, 7270 Davos, Switzerland
| | - Mauro Alini
- AO Research Institute, Clavadelerstrasse 8, 7270 Davos, Switzerland
| | - Dimitrios I Zeugolis
- Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, National University of Ireland Galway (NUI Galway), Galway, Ireland.
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Salam N, Toumpaniari S, Gentile P, Marina Ferreira A, Dalgarno K, Partridge S. Assessment of Migration of Human MSCs through Fibrin Hydrogels as a Tool for Formulation Optimisation. MATERIALS 2018; 11:ma11091781. [PMID: 30235852 PMCID: PMC6164849 DOI: 10.3390/ma11091781] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Revised: 09/15/2018] [Accepted: 09/17/2018] [Indexed: 12/13/2022]
Abstract
Control of cell migration is fundamental to the performance of materials for cell delivery, as for cells to provide any therapeutic effect, they must migrate out from the delivery material. Here the influence of fibrinogen concentration on the migration of encapsulated human mesenchymal stem cells (hMSCs) from a cell spheroid through fibrin hydrogels is tracked over time. Fibrin was chosen as a model material as it is routinely employed as a haemostatic agent and more recently has been applied as a localised delivery vehicle for potential therapeutic cell populations. The hydrogels consisted of 5 U/mL thrombin and between 5 and 50 mg/mL fibrinogen. Microstructural and viscoelastic properties of different compositions were evaluated using SEM and rheometry. Increasing the fibrinogen concentration resulted in a visibly denser matrix with smaller pores and higher stiffness. hMSCs dispersed within the fibrin gels maintained cell viability post-encapsulation, however, the migration of cells from an encapsulated spheroid revealed that denser fibrin matrices inhibit cell migration. This study provides the first quantitative study on the influence of fibrinogen concentration on 3D hMSC migration within fibrin gels, which can be used to guide material selection for scaffold design in tissue engineering and for the clinical application of fibrin sealants.
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Affiliation(s)
- Nasseem Salam
- School of Medicine Medical Sciences and Nutrition, University of Aberdeen, King's College, Aberdeen AB24 3FX, UK.
| | - Sotiria Toumpaniari
- Department of Materials Science and Metallurgy, University of Cambridge, 27 Charles Babbage Road, Cambridge CB3 0FS, UK.
| | - Piergiorgio Gentile
- School of Engineering, Newcastle University, Newcastle upon Tyne NE1 7RU, UK.
| | - Ana Marina Ferreira
- School of Engineering, Newcastle University, Newcastle upon Tyne NE1 7RU, UK.
| | - Kenneth Dalgarno
- School of Engineering, Newcastle University, Newcastle upon Tyne NE1 7RU, UK.
| | - Simon Partridge
- Materials and Engineering Research Institute, Sheffield Hallam University, City Campus, Howard Street, Sheffield S1 1WB, UK.
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Cengiz IF, Pereira H, de Girolamo L, Cucchiarini M, Espregueira-Mendes J, Reis RL, Oliveira JM. Orthopaedic regenerative tissue engineering en route to the holy grail: disequilibrium between the demand and the supply in the operating room. J Exp Orthop 2018; 5:14. [PMID: 29790042 PMCID: PMC5964057 DOI: 10.1186/s40634-018-0133-9] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2017] [Accepted: 05/17/2018] [Indexed: 12/13/2022] Open
Abstract
Orthopaedic disorders are very frequent, globally found and often partially unresolved despite the substantial advances in science and medicine. Their surgical intervention is multifarious and the most favourable treatment is chosen by the orthopaedic surgeon on a case-by-case basis depending on a number of factors related with the patient and the lesion. Numerous regenerative tissue engineering strategies have been developed and studied extensively in laboratory through in vitro experiments and preclinical in vivo trials with various established animal models, while a small proportion of them reached the operating room. However, based on the available literature, the current strategies have not yet achieved to fully solve the clinical problems. Thus, the gold standards, if existing, remain unchanged in the clinics, notwithstanding the known limitations and drawbacks. Herein, the involvement of regenerative tissue engineering in the clinical orthopaedics is reviewed. The current challenges are indicated and discussed in order to describe the current disequilibrium between the needs and solutions made available in the operating room. Regenerative tissue engineering is a very dynamic field that has a high growth rate and a great openness and ability to incorporate new technologies with passion to edge towards the Holy Grail that is functional tissue regeneration. Thus, the future of clinical solutions making use of regenerative tissue engineering principles for the management of orthopaedic disorders is firmly supported by the clinical need.
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Affiliation(s)
- Ibrahim Fatih Cengiz
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal. .,ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
| | - Hélder Pereira
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal.,ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.,Ripoll y De Prado Sports Clinic: Murcia-Madrid FIFA Medical Centre of Excellence, Madrid, Spain.,Orthopedic Department Centro Hospitalar Póvoa de Varzim, Vila do Conde, Portugal
| | - Laura de Girolamo
- Orthopaedic Biotechnology Laboratory, IRCCS Galeazzi Orthopaedic Institute, Milan, Italy
| | - Magali Cucchiarini
- Center of Experimental Orthopaedics, Saarland University Medical Center, Kirrbergerstr Bldg 37, D-66421, Homburg/Saar, Germany
| | - João Espregueira-Mendes
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal.,ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.,Clínica do Dragão, Espregueira-Mendes Sports Centre - FIFA Medical Centre of Excellence, Porto, Portugal.,Dom Henrique Research Centre, Porto, Portugal.,Orthopedic Department, University of Minho, Braga, Portugal
| | - Rui L Reis
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal.,ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.,The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Avepark, 4805-017 Barco, Guimarães, Portugal
| | - Joaquim Miguel Oliveira
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal.,ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.,Clínica do Dragão, Espregueira-Mendes Sports Centre - FIFA Medical Centre of Excellence, Porto, Portugal.,The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Avepark, 4805-017 Barco, Guimarães, Portugal
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Synthetic Materials for Osteochondral Tissue Engineering. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 1058:31-52. [DOI: 10.1007/978-3-319-76711-6_2] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Kreuz PC, Kalkreuth RH, Niemeyer P, Uhl M, Erggelet C. Treatment of a Focal Articular Cartilage Defect of the Talus with Polymer-Based Autologous Chondrocyte Implantation: A 12-Year Follow-Up Period. J Foot Ankle Surg 2018. [PMID: 28633793 DOI: 10.1053/j.jfas.2017.03.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Autologous chondrocyte implantation (ACI) is a first-line treatment option for large articular cartilage defects. Although well-established for cartilage defects in the knee, studies of the long-term outcomes of matrix-assisted ACI to treat cartilage defects in the ankle are rare. In the present report, we describe for the first time the long-term clinical and radiologic results 12 years after polymer-based matrix-assisted ACI treat a full-thickness talar cartilage defect in a 25-year-old male patient. The clinical outcome was assessed using the visual analog scale and Freiburg ankle score, magnetic resonance imaging evaluation using the Henderson-Kreuz scoring system and T2 mapping. Clinical assessment revealed improved visual analog scale and Freiburg ankle scores. The radiologic analysis and T2 relaxation time values indicated the formation of hyaline-like repair tissue. Polymer-based autologous chondrocytes has been shown to be a safe and clinically effective long-term treatment of articular cartilage defects in the talus.
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Affiliation(s)
- Peter Cornelius Kreuz
- Professor, Orthopaedic Surgeon, Department of Orthopaedic Surgery, University Medical Center Rostock, Rostock, Germany
| | - Richard Horst Kalkreuth
- Medical Student, Department of Orthopedic Surgery and Traumatology, Freiburg University Hospital, Freiburg, Germany.
| | - Philipp Niemeyer
- Professor, Orthopaedic Surgeon, Department of Orthopedic Surgery and Traumatology, Freiburg University Hospital, Freiburg, Germany
| | - Markus Uhl
- Professor, Clinical Radiologist, Department of Radiology, RKK-Klinikum Freiburg, Freiburg, Germany
| | - Christoph Erggelet
- Professor, Orthopaedic Surgeon, alphaclinic Zurich, International Centers for Sports Medicine and Joint Surgery, Zurich, Switzerland
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Bicho D, Pina S, Reis RL, Oliveira JM. Commercial Products for Osteochondral Tissue Repair and Regeneration. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 1058:415-428. [PMID: 29691833 DOI: 10.1007/978-3-319-76711-6_19] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
The osteochondral tissue represents a complex structure composed of four interconnected structures, namely hyaline cartilage, a thin layer of calcified cartilage, subchondral bone, and cancellous bone. Due to the several difficulties associated with its repair and regeneration, researchers have developed several studies aiming to restore the native tissue, some of which had led to tissue-engineered commercial products. In this sense, this chapter discusses the good manufacturing practices, regulatory medical conditions and challenges on clinical translations that should be fulfilled regarding the safety and efficacy of the new commercialized products. Furthermore, we review the current osteochondral products that are currently being marketed and applied in the clinical setting, emphasizing the advantages and difficulties of each one.
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Affiliation(s)
- Diana Bicho
- 3B's Research Group-Biomaterials, Biodegradables and Biomimetics, European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho, Barco GMR, Portugal. .,ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
| | - Sandra Pina
- 3B's Research Group-Biomaterials, Biodegradables and Biomimetics, European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho, Barco GMR, Portugal.,ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Rui L Reis
- 3B's Research Group-Biomaterials, Biodegradables and Biomimetics, European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho, Barco GMR, Portugal.,ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.,The Discoveries Centre for Regenerative and Precision Medicine, University of Minho, Barco, Guimarães, Portugal
| | - J Miguel Oliveira
- 3B's Research Group-Biomaterials, Biodegradables and Biomimetics, European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho, Barco GMR, Portugal.,ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.,The Discoveries Centre for Regenerative and Precision Medicine, University of Minho, Barco, Guimarães, Portugal
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Coleman MC, Brouillette MJ, Andresen NS, Oberley-Deegan RE, Martin JM. Differential Effects of Superoxide Dismutase Mimetics after Mechanical Overload of Articular Cartilage. Antioxidants (Basel) 2017; 6:E98. [PMID: 29189731 PMCID: PMC5745508 DOI: 10.3390/antiox6040098] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2017] [Revised: 11/20/2017] [Accepted: 11/28/2017] [Indexed: 01/17/2023] Open
Abstract
Post-traumatic osteoarthritis can develop as a result of the initial mechanical impact causing the injury and also as a result of chronic changes in mechanical loading of the joint. Aberrant mechanical loading initiates excessive production of reactive oxygen species, oxidative damage, and stress that appears to damage mitochondria in the surviving chondrocytes. To probe the benefits of increasing superoxide removal with small molecular weight superoxide dismutase mimetics under severe loads, we applied both impact and overload injury scenarios to bovine osteochondral explants using characterized mechanical platforms with and without GC4403, MnTE-2-PyP, and MnTnBuOE-2-PyP. In impact scenarios, each of these mimetics provides some dose-dependent protection from cell death and loss of mitochondrial content while in repeated overloading scenarios only MnTnBuOE-2-PyP provided a clear benefit to chondrocytes. These results support the hypothesis that superoxide is generated in excess after impact injuries and suggest that superoxide production within the lipid compartment may be a critical mediator of responses to chronic overload. This is an important nuance distinguishing roles of superoxide, and thus superoxide dismutases, in mediating damage to cellular machinery in hyper-acute impact scenarios compared to chronic scenarios.
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Affiliation(s)
- Mitchell C Coleman
- Department of Orthopedics and Rehabilitation, University of Iowa, Iowa City, IA 52242, USA.
| | - Marc J Brouillette
- Department of Orthopedics and Rehabilitation, University of Iowa, Iowa City, IA 52242, USA.
| | - Nicholas S Andresen
- Department of Orthopedics and Rehabilitation, University of Iowa, Iowa City, IA 52242, USA.
| | - Rebecca E Oberley-Deegan
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
| | - James M Martin
- Department of Orthopedics and Rehabilitation, University of Iowa, Iowa City, IA 52242, USA.
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Bell AD, Hurtig MB, Quenneville E, Rivard GÉ, Hoemann CD. Effect of a Rapidly Degrading Presolidified 10 kDa Chitosan/Blood Implant and Subchondral Marrow Stimulation Surgical Approach on Cartilage Resurfacing in a Sheep Model. Cartilage 2017; 8:417-431. [PMID: 28934884 PMCID: PMC5613897 DOI: 10.1177/1947603516676872] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Objective This study tested the hypothesis that presolidified chitosan-blood implants are retained in subchondral bone channels perforated in critical-size sheep cartilage defects, and promote bone repair and hyaline-like cartilage resurfacing versus blood implant. Design Cartilage defects (10 × 10 mm) with 3 bone channels (1 drill, 2 Jamshidi biopsy, 2 mm diameter), and 6 small microfracture holes were created bilaterally in n = 11 sheep knee medial condyles. In one knee, 10 kDa chitosan-NaCl/blood implant (presolidified using recombinant factor VIIa or tissue factor), was inserted into each drill and Jamshidi hole. Contralateral knee defects received presolidified whole blood clot. Repair tissues were assessed histologically, biochemically, biomechanically, and by micro-computed tomography after 1 day ( n = 1) and 6 months ( n = 10). Results Day 1 defects showed a 60% loss of subchondral bone plate volume fraction along with extensive subchondral hematoma. Chitosan implant was resident at day 1, but had no effect on any subsequent repair parameter compared with blood implant controls. At 6 months, bone defects exhibited remodeling and hypomineralized bone repair and were partly resurfaced with tissues containing collagen type II and scant collagen type I, 2-fold lower glycosaminoglycan and fibril modulus, and 4.5-fold higher permeability compared with intact cartilage. Microdrill holes elicited higher histological ICRS-II overall assessment scores than Jamshidi holes (50% vs. 30%, P = 0.041). Jamshidi biopsy holes provoked sporadic osteonecrosis in n = 3 debrided condyles. Conclusions Ten kilodalton chitosan was insufficient to improve repair. Microdrilling is a feasible subchondral marrow stimulation surgical approach with the potential to elicit poroelastic tissues with at least half the compressive modulus as intact articular cartilage.
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Affiliation(s)
- Angela D. Bell
- Department of Clinical Studies, University of Guelph, Guelph, Ontario, Canada
| | - Mark B. Hurtig
- Department of Clinical Studies, University of Guelph, Guelph, Ontario, Canada
| | | | | | - Caroline D. Hoemann
- Department of Chemical Engineering, Institute of Biomedical Engineering, Ecole Polytechnique, Montreal, Quebec, Canada,Caroline D. Hoemann, Department of Chemical Engineering, Institute of Biomedical Engineering, École Polytechnique, Montreal, Quebec, H3C 3A7, Canada.
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Flórez Cabrera A, González Duque MI, Fontanlla MR. Terapias Celulares y Productos de Ingeniería de Tejidos para el Tratamiento de Lesiones Condrales de Rodilla. REVISTA COLOMBIANA DE BIOTECNOLOGÍA 2017. [DOI: 10.15446/rev.colomb.biote.v19n2.70276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
El cartílago articular es un tejido vulnerable a las lesiones de diferente etiología; siendo uno de los más afectados, el cartílago de la rodilla. Aunque la mayoría de los tratamientos convencionales reducen los síntomas, generalmente conducen a la formación de fibrocartílago; el cual, posee características diferentes a las del cartílago hialino de las articulaciones. Son pocas las aproximaciones terapéuticas que promueven el reemplazo del tejido dañado por cartílago hialino funcional; las más exitosas son las denominadas terapias avanzadas, que aplican células y productos de ingeniería de tejidos con el fin de estimular la regeneración del cartílago. La mayoría de ellas se basan en colocar soportes hechos con biomateriales de diferente origen, que sembrados o no con células exógenas o endógenas, reemplazan al cartílago dañado y promueven su regeneración. Este trabajo revisa algunas de las aproximaciones terapéuticas enfocadas en la regeneración del cartílago articular de rodilla; así como, los biomateriales más empleados en la elaboración de soportes para terapia celular e ingeniería de tejido cartilaginoso.
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Zeineddine HA, Frush TJ, Saleh ZM, El-Othmani MM, Saleh KJ. Applications of Tissue Engineering in Joint Arthroplasty: Current Concepts Update. Orthop Clin North Am 2017; 48:275-288. [PMID: 28577777 DOI: 10.1016/j.ocl.2017.03.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Research in tissue engineering has undoubtedly achieved significant milestones in recent years. Although it is being applied in several disciplines, tissue engineering's application is particularly advanced in orthopedic surgery and in degenerative joint diseases. The literature is full of remarkable findings and trials using tissue engineering in articular cartilage disease. With the vast and expanding knowledge, and with the variety of techniques available at hand, the authors aimed to review the current concepts and advances in the use of cell sources in articular cartilage tissue engineering.
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Affiliation(s)
- Hussein A Zeineddine
- Department of Surgery, University of Chicago Medical Center, 5841 South Maryland Avenue, Chicago, IL 60637, USA
| | - Todd J Frush
- Department of Orthopaedics and Sports Medicine, Detroit Medical Center, University Health Center (UHC) 9B, 4201 Saint Antoine Street, Detroit, MI 48201-2153, USA
| | - Zeina M Saleh
- Department of Surgery, American University of Beirut Medical Center, Bliss Street, Riad El-Solh, Beirut 11072020, Lebanon
| | - Mouhanad M El-Othmani
- Department of Orthopaedics and Sports Medicine, Musculoskeletal Institute of Excellence, Detroit Medical Center, University Health Center (UHC) 9B, 4201 Saint Antoine Street, Detroit, MI 48201-2153, USA
| | - Khaled J Saleh
- Department of Orthopaedics and Sports Medicine, Detroit Medical Center, University Health Center (UHC) 9B, 4201 Saint Antoine Street, Detroit, MI 48201-2153, USA.
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Ebert JR, Edwards PK, Fallon M, Ackland TR, Janes GC, Wood DJ. Two-Year Outcomes of a Randomized Trial Investigating a 6-Week Return to Full Weightbearing After Matrix-Induced Autologous Chondrocyte Implantation. Am J Sports Med 2017; 45:838-848. [PMID: 27881381 DOI: 10.1177/0363546516673837] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Matrix-induced autologous chondrocyte implantation (MACI) has demonstrated encouraging outcomes in treating patients with knee cartilage defects. Postoperatively, the time required to attain full weightbearing (WB) remains conservative. HYPOTHESIS We hypothesized that patients would have no significant clinical or radiological differences or graft complications after an 8-week or 6-week return to full WB after MACI. STUDY DESIGN Randomized controlled trial; Level of evidence, 1. METHODS A total of 37 knees (n = 35 patients) were randomly allocated to either an 8-week return to full WB that we considered current best practice based on the existing literature (CR group; n = 19 knees) or an accelerated 6-week WB approach (AR group; n = 18 knees). Patients were evaluated preoperatively and at 1, 2, 3, 6, 12, and 24 months after surgery, using the Knee Injury and Osteoarthritis Outcome Score, 36-Item Short Form Health Survey, visual analog pain scale, 6-minute walk test, and active knee range of motion. Isokinetic dynamometry was used to assess peak knee extension and flexion strength and limb symmetry indices (LSIs) between the operated and nonoperated limbs. Magnetic resonance imaging (MRI) was undertaken to evaluate the quality and quantity of repair tissue as well as to calculate an MRI composite score. RESULTS Significant improvements ( P < .05) were observed in all subjective scores, active knee flexion and extension, 6-minute capacity, peak knee extensor torque in the operated limb, and knee extensor LSI, although no group differences existed. Although knee flexor LSIs were above 100% for both groups at 12 and 24 months after surgery, LSIs for knee extensor torque at 24 months were 93.7% and 87.5% for the AR and CR groups, respectively. The MRI composite score and pertinent graft parameters significantly improved over time ( P < .05), with some superior in the AR group at 24 months. All patients in the AR group (100%) demonstrated good to excellent infill at 24 months, compared with 83% of patients in the CR group. Two cases of graft failure were observed, both in the CR group. At 24 months, 83% of patients in the CR group and 88% in the AR group were satisfied with the results of their MACI surgery. CONCLUSION Patients in the AR group who reduced the length of time spent ambulating on crutches produced comparable outcomes up to 24 months, without compromising graft integrity.
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Affiliation(s)
- Jay R Ebert
- School of Sport Science, Exercise and Health, University of Western Australia, Crawley, Australia
| | - Peter K Edwards
- School of Sport Science, Exercise and Health, University of Western Australia, Crawley, Australia
| | | | - Timothy R Ackland
- School of Sport Science, Exercise and Health, University of Western Australia, Crawley, Australia
| | - Gregory C Janes
- Perth Orthopaedic and Sports Medicine Centre, West Perth, Australia
| | - David J Wood
- School of Surgery (Orthopaedics), University of Western Australia, Crawley, Australia
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Ebert JR, Fallon M, Wood DJ, Janes GC. A Prospective Clinical and Radiological Evaluation at 5 Years After Arthroscopic Matrix-Induced Autologous Chondrocyte Implantation. Am J Sports Med 2017; 45:59-69. [PMID: 27587741 DOI: 10.1177/0363546516663493] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND While midterm outcomes after matrix-induced autologous chondrocyte implantation (MACI) are encouraging, the procedure permits an arthroscopic approach that may reduce the morbidity of arthrotomy and permit accelerated rehabilitation. HYPOTHESIS A significant improvement in clinical and radiological outcomes after arthroscopic MACI will exist through to 5 years after surgery. STUDY DESIGN Case series; Level of evidence, 4. METHODS We prospectively evaluated the first 31 patients (15 male, 16 female) who underwent MACI via arthroscopic surgery to address symptomatic tibiofemoral chondral lesions. MACI was followed by a structured rehabilitation program in all patients. Clinical scores were administered preoperatively and at 3 and 6 months as well as 1, 2, and 5 years after surgery. These included the Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm knee scale (LKS), Tegner activity scale (TAS), visual analog scale for pain, Short Form-36 Health Survey (SF-36), active knee motion, and 6-minute walk test. Isokinetic dynamometry was used to assess peak knee extension and flexion strength and limb symmetry indices (LSIs) between the operated and nonoperated limbs. High-resolution magnetic resonance imaging (MRI) was performed at 3 months and at 1, 2, and 5 years postoperatively to evaluate graft repair as well as calculate the MRI composite score. RESULTS There was a significant improvement ( P < .05) in all KOOS subscale scores, LKS and TAS scores, the SF-36 physical component score, pain frequency and severity, active knee flexion and extension, and 6-minute walk distance. Isokinetic knee extension strength significantly improved, and all knee extension and flexion LSIs were above 90% (apart from peak knee extension strength at 1 year). At 5 years, 93% of patients were satisfied with MACI to relieve their pain, 90% were satisfied with improving their ability to undertake daily activities, and 80% were satisfied with the improvement in participating in sport. Graft infill ( P = .033) and the MRI composite score ( P = .028) significantly improved over time, with 90% of patients demonstrating good to excellent tissue infill at 5 years. There were 2 graft failures at 5 years after surgery. CONCLUSION The arthroscopically performed MACI technique demonstrated good clinical and radiological outcomes up to 5 years, with high levels of patient satisfaction.
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Affiliation(s)
- Jay R Ebert
- School of Sport Science, Exercise and Health, University of Western Australia, Crawley, Australia
| | | | - David J Wood
- School of Surgery (Orthopaedics), University of Western Australia, Crawley, Australia
| | - Gregory C Janes
- Perth Orthopaedic and Sports Medicine Centre, West Perth, Australia
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Narayanan G, Vernekar VN, Kuyinu EL, Laurencin CT. Poly (lactic acid)-based biomaterials for orthopaedic regenerative engineering. Adv Drug Deliv Rev 2016; 107:247-276. [PMID: 27125191 PMCID: PMC5482531 DOI: 10.1016/j.addr.2016.04.015] [Citation(s) in RCA: 253] [Impact Index Per Article: 28.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2016] [Revised: 03/09/2016] [Accepted: 04/17/2016] [Indexed: 02/07/2023]
Abstract
Regenerative engineering converges tissue engineering, advanced materials science, stem cell science, and developmental biology to regenerate complex tissues such as whole limbs. Regenerative engineering scaffolds provide mechanical support and nanoscale control over architecture, topography, and biochemical cues to influence cellular outcome. In this regard, poly (lactic acid) (PLA)-based biomaterials may be considered as a gold standard for many orthopaedic regenerative engineering applications because of their versatility in fabrication, biodegradability, and compatibility with biomolecules and cells. Here we discuss recent developments in PLA-based biomaterials with respect to processability and current applications in the clinical and research settings for bone, ligament, meniscus, and cartilage regeneration.
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Affiliation(s)
- Ganesh Narayanan
- Institute for Regenerative Engineering, University of Connecticut Health Center, Farmington, CT 06030, USA; Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA; Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT 06030, USA
| | - Varadraj N Vernekar
- Institute for Regenerative Engineering, University of Connecticut Health Center, Farmington, CT 06030, USA; Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA; Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT 06030, USA
| | - Emmanuel L Kuyinu
- Institute for Regenerative Engineering, University of Connecticut Health Center, Farmington, CT 06030, USA; Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA; Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT 06030, USA
| | - Cato T Laurencin
- Institute for Regenerative Engineering, University of Connecticut Health Center, Farmington, CT 06030, USA; Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA; Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT 06030, USA; School of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA; Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA; Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT 06269, USA; Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USA; Department of Materials Science and Engineering, University of Connecticut, Storrs, CT 06269, USA.
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Abstract
Background and purpose - Cartilage damage can develop due to trauma, resulting in focal chondral or osteochondral defects, or as more diffuse loss of cartilage in a generalized organ disease such as osteoarthritis. A loss of cartilage function and quality is also seen with increasing age. There is a spectrum of diseases ranging from focal cartilage defects with healthy surrounding cartilage to focal lesions in degenerative cartilage, to multiple and diffuse lesions in osteoarthritic cartilage. At the recent Aarhus Regenerative Orthopaedics Symposium (AROS) 2015, regenerative challenges in an ageing population were discussed by clinicians and basic scientists. A group of clinicians was given the task of discussing the role of tissue engineering in the treatment of degenerative cartilage lesions in ageing patients. We present the outcomes of our discussions on current treatment options for such lesions, with particular emphasis on different biological repair techniques and their supporting level of evidence. Results and interpretation - Based on the studies on treatment of degenerative lesions and early OA, there is low-level evidence to suggest that cartilage repair is a possible treatment for such lesions, but there are conflicting results regarding the effect of advanced age on the outcome. We concluded that further improvements are needed for direct repair of focal, purely traumatic defects before we can routinely use such repair techniques for the more challenging degenerative lesions. Furthermore, we need to identify trigger mechanisms that start generalized loss of cartilage matrix, and induce subchondral bone changes and concomitant synovial pathology, to maximize our treatment methods for biological repair in degenerative ageing joints.
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Affiliation(s)
- Mats Brittberg
- Cartilage Research Unit, University of Gothenburg, Region Halland Orthopaedics, Kungsbacka Hospital, Kungsbacka, Sweden,Correspondence:
| | - Andreas H Gomoll
- Harvard Medical School, Cartilage Repair Center, Brigham and Women’s Hospital, Boston, MA
| | - José A Canseco
- Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA
| | - Jack Far
- Indiana University School of Medicine, OrthoIndy Cartilage Restoration Center, Indianapolis, IN, USA
| | - Martin Lind
- Division of Sports Traumatology, Department of Orthopedics, Aarhus University Hospital, Århus, Denmark
| | - James Hui
- Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University Singapore, Singapore
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Gille J, Behrens P, Schulz AP, Oheim R, Kienast B. Matrix-Associated Autologous Chondrocyte Implantation: A Clinical Follow-Up at 15 Years. Cartilage 2016; 7:309-15. [PMID: 27688839 PMCID: PMC5029570 DOI: 10.1177/1947603516638901] [Citation(s) in RCA: 64] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
INTRODUCTION A prospective clinical investigation was carried out in order to clarify whether Matrix-associated autologous chondrocyte implantation (MACI) results in clinical improvement at long-term follow-up. HYPOTHESIS MACI will result in clinical improvement at long-term follow-up. STUDY DESIGN Case series; level of evidence, 4. METHODS Thirty-eight patients were treated with MACI. These patients were evaluated for up to a mean of 16 years (range 15-17 years) after the intervention. Three different scores (Lysholm-Gilquist score, International Cartilage Repair Society score, and Tegner score) formed the basis of this study. Overall, we were able to obtain valid preoperative and postoperative results from 18 (47%) of 38 patients. In 1 patient, both knees were treated. In 4 patients, an arthroplasty was implanted over the course of time; thus they were excluded from this case series. In conclusion, follow-up of 15 knees was performed in the recent series. RESULTS In subjective rating, 12 out of 14 patients (86%) rated the function of their knee as much better or better than before the index procedure. All numerical outcome scores showed significant improvement compared to the preoperative value (preoperative/postoperative at 5 years/postoperative at 15 years): Lysholm score 59.6 (±24.6)/78.6 (±21.5)/82.7 (±11.3), International Knee Documentation Committee score 50.6 (±22.7)/64.7 (±21.6)/69.7 (±18.7), Tegner score 3.0 (±2.2)/3.6 (±1.5)/5.2 (±1.7). CONCLUSION The significantly improved results on 3 scores after 15 years suggest that MACI represents a suitable treatment of local cartilage defects in the knee.
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Affiliation(s)
- Justus Gille
- University of Schleswig-Holstein, Luebeck, Germany,Justus Gille, University of Schleswig-Holstein, Ratzeburger Allee 160, Luebeck, 23538, Germany.
| | | | | | - Ralf Oheim
- BG Trauma Hospital Hamburg, Hamburg, Germany
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Cross LM, Thakur A, Jalili NA, Detamore M, Gaharwar AK. Nanoengineered biomaterials for repair and regeneration of orthopedic tissue interfaces. Acta Biomater 2016; 42:2-17. [PMID: 27326917 DOI: 10.1016/j.actbio.2016.06.023] [Citation(s) in RCA: 87] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2016] [Revised: 06/07/2016] [Accepted: 06/16/2016] [Indexed: 12/21/2022]
Abstract
UNLABELLED Orthopedic interface tissue engineering aims to mimic the structure and function of soft-to-hard tissue junctions, particularly bone-ligament, bone-tendon, and bone-cartilage interfaces. A range of engineering approaches has been proposed to mimic the gradient architecture, physical properties and chemical characteristics of interface tissues using conventional polymeric biomaterials. Recent developments in nanomaterials and nanofabrication technologies introduce a range of synthesis and fabrication tools to effectively engineer the structure and function of native tissue interfaces. In this review, we will focus on nanoengineered strategies used to replicate the structural and functional aspects of native biological tissues for engineering bone-cartilage, bone-ligament, and bone-tendon interfaces. This review will also highlight some of the emerging applications and future potential of nanomaterials and fabrication technologies in engineering tissue interfaces. STATEMENT OF SIGNIFICANCE A major challenge in engineering interfaces is to control the physical and structural characteristics of an artificial environment. The use of nanomaterials and nanoengineered strategies allow for greater control over the changes in structure and function at molecular and nanometer length scale. This review focuses on advanced nanomaterials and nanofabrication approaches developed to emulate bone-cartilage, bone-ligament, and bone-tendon interface regions. Some of the emerging nanoengineered biomaterials proposed to mimic tissue interfaces are also highlighted.
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Affiliation(s)
- Lauren M Cross
- Department of Biomedical Engineering, Texas A&M University, College Station, TX 77841, USA
| | - Ashish Thakur
- Department of Biomedical Engineering, Texas A&M University, College Station, TX 77841, USA
| | - Nima A Jalili
- Department of Biomedical Engineering, Texas A&M University, College Station, TX 77841, USA
| | - Michael Detamore
- Department of Chemical and Petroleum Engineering, University of Kansas, Lawrence, KS 66045, USA
| | - Akhilesh K Gaharwar
- Department of Biomedical Engineering, Texas A&M University, College Station, TX 77841, USA; Department of Materials Science and Engineering, Texas A&M University, College Station, TX 77841, USA; Center for Remote Health Technologies and Systems, Texas A&M University, College Station, TX 77843, USA.
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Sun AX, Numpaisal PO, Gottardi R, Shen H, Yang G, Tuan RS. Cell and Biomimetic Scaffold-Based Approaches for Cartilage Regeneration. ACTA ACUST UNITED AC 2016. [DOI: 10.1053/j.oto.2016.06.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Aae TF, Randsborg PH, Breen AB, Visnes H, Vindfeld S, Sivertsen EA, Løken S, Brinchmann J, Hanvold HA, Årøen A. Norwegican Cartilage Project - a study protocol for a double-blinded randomized controlled trial comparing arthroscopic microfracture with arthroscopic debridement in focal cartilage defects in the knee. BMC Musculoskelet Disord 2016; 17:292. [PMID: 27422025 PMCID: PMC4947343 DOI: 10.1186/s12891-016-1156-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2016] [Accepted: 07/02/2016] [Indexed: 01/30/2023] Open
Abstract
Background Focal lesions to the articular cartilage in the knee might have demolishing consequences to the knee. There exists a wide range of possible surgical procedures targeting these injuries, however no significant differences have been found between these procedures. This may support that the improvement is a result of rehabilitation, and not the surgery itself. Arthroscopic microfracture (MF) treatment has gained popularity, and has become the treatment of choice in patients with knee cartilage defects globally. In this study we want to increase knowledge, both clinical and economic, about arthroscopic microfracture (AF) compared to arthroscopic debridement (AD) and physical rehabilitation both in the short run, and in the long run. Methods/Design To compare arthroscopic microfracture with arthroscopic debridement and physiotherapy for the treatment of focal cartilage lesions in the knee, a long-term, double-blinded, randomized controlled multicenter trial will be conducted. A total of 114 men and non-pregnant women with a symptomatic focal full thickness cartilage lesion in the knee less than 2 cm2 will be included in the study. The two treatment allocations will receive identical rehabilitation, which is made up of 3 phases: accommodation, rehabilitation and return to activity. Follow up is 24 months, where all will be invited to participate in late follow ups after 5 and 10 years. The Knee Injury and Osteoarthritis Outcome Score (KOOS) knee-related quality of life (QoL) subscore is the primary endpoint. Clinical parameters, questionnaires and radiologic modalities (Magnetic Resonance Imaging (MRI) and x-ray) will be used as secondary endpoints. Discussion This is an ongoing multicenter study with a high level of evidence to compare arthroscopic microfracture with arthroscopic debridement and physiotherapy for the treatment of isolated symptomatic full thickness cartilage lesions in the knee joint. Trial registration ClinicalTrials.gov ID: NCT02637505 (December 15, 2015).
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Affiliation(s)
- Tommy Frøseth Aae
- Department of Orthopedic Surgery, Kristiansund Hospital, Kristiansund, Norway.
| | - Per-Henrik Randsborg
- Department of Orthopedic Surgery, Akershus University Hospital, Lørenskog, Norway
| | - Anne Berg Breen
- Department of Orthopedic Surgery, Ålesund Hospital, Ålesund, Norway
| | - Håvard Visnes
- Department of Orthopedic Surgery, Haukeland University Hospital, Bergen, Norway
| | - Søren Vindfeld
- Department of Orthopedic Surgery, Haraldsplass Deaconess Hospital, Deaconess, Norway
| | | | - Sverre Løken
- Department of Orthopedics, Oslo University Hospital, Oslo, Norway
| | - Jan Brinchmann
- Department of Immunology and Norwegian Center for Stem Cell Research, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | | | - Asbjørn Årøen
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Oslo Sports Trauma Research Centre, Norwegian School of Sport Sciences, Oslo, Norway
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