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1
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Jiang Y, Li T, Liu B, Tian Y, Wang Y, Li T, Zhang D. Soyasaponin Bb/Gelatin-Methacryloyl Hydrogel for Cartilage Inflammation Inhibition. ACS OMEGA 2024; 9:49597-49608. [PMID: 39713654 PMCID: PMC11656367 DOI: 10.1021/acsomega.4c07489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 10/08/2024] [Accepted: 11/27/2024] [Indexed: 12/24/2024]
Abstract
The main causes of failure for cartilage tissue engineering implants are tissue integration, inflammation, and infection. The development of biomaterials with antiforeign body response (FBR) is of particular importance. Herein, we developed a hydrogel loaded with anti-inflammatory drugs to reduce the inflammatory response that follows implantation. The human chondrocytes were used for in vitro study, and cell-laden hydrogel samples were implanted with the backs of rabbits for in vivo study. Soyasaponin Bb (SsBb) as a traditional Chinese medicine could significantly (P < 0.05) downregulate the expression levels of inflammation-related markers including iNOS, COX-2, and IL-6 in chondrocytes induced by IL-1β through the NF-κB signaling pathway. The in vitro experiments demonstrated that a gelatin-methacryloyl (GelMA) hydrogel loaded with SsBb (SsBb/GelMA) could similarly reduce the gene and protein expression levels of inflammation-related markers (iNOS, COX-2, and IL-6). The in vivo anti-inflammatory effects of the SsBb/GelMA hydrogels were assessed by immunohistochemical staining. The results demonstrated that SsBb/GelMA hydrogels inhibited the inflammatory response and downregulated the expression of the inflammatory cytokine IL-6. Therefore, SsBb/GelMA hydrogels are promising candidates for promoting anti-inflammation and cartilage tissue regeneration of implant surfaces.
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Affiliation(s)
- Yuhan Jiang
- Department of Plastic and
Reconstructive Surgery, The First Hospital
of Jilin University, Changchun 130021, P. R. China
| | - Tenghai Li
- Department of Plastic and
Reconstructive Surgery, The First Hospital
of Jilin University, Changchun 130021, P. R. China
| | - Bingzhang Liu
- Department of Plastic and
Reconstructive Surgery, The First Hospital
of Jilin University, Changchun 130021, P. R. China
| | - Yufeng Tian
- Department of Plastic and
Reconstructive Surgery, The First Hospital
of Jilin University, Changchun 130021, P. R. China
| | - Yixin Wang
- Department of Plastic and
Reconstructive Surgery, The First Hospital
of Jilin University, Changchun 130021, P. R. China
| | - Tian Li
- Department of Plastic and
Reconstructive Surgery, The First Hospital
of Jilin University, Changchun 130021, P. R. China
| | - Duo Zhang
- Department of Plastic and
Reconstructive Surgery, The First Hospital
of Jilin University, Changchun 130021, P. R. China
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2
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Wang A, Ma X, Bian J, Jiao Z, Zhu Q, Wang P, Zhao Y. Signalling pathways underlying pulsed electromagnetic fields in bone repair. Front Bioeng Biotechnol 2024; 12:1333566. [PMID: 38328443 PMCID: PMC10847561 DOI: 10.3389/fbioe.2024.1333566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Accepted: 01/15/2024] [Indexed: 02/09/2024] Open
Abstract
Pulsed electromagnetic field (PEMF) stimulation is a prospective non-invasive and safe physical therapy strategy for accelerating bone repair. PEMFs can activate signalling pathways, modulate ion channels, and regulate the expression of bone-related genes to enhance osteoblast activity and promote the regeneration of neural and vascular tissues, thereby accelerating bone formation during bone repair. Although their mechanisms of action remain unclear, recent studies provide ample evidence of the effects of PEMF on bone repair. In this review, we present the progress of research exploring the effects of PEMF on bone repair and systematically elucidate the mechanisms involved in PEMF-induced bone repair. Additionally, the potential clinical significance of PEMF therapy in fracture healing is underscored. Thus, this review seeks to provide a sufficient theoretical basis for the application of PEMFs in bone repair.
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Affiliation(s)
- Aoao Wang
- Medical School of Chinese PLA, Beijing, China
| | - Xinbo Ma
- Department of Chemistry, Capital Normal University, Beijing, China
| | - Jiaqi Bian
- Senior Department of Orthopaedics, The Fourth Medical Center of PLA General Hospital, Beijing, China
| | | | - Qiuyi Zhu
- Medical School of Chinese PLA, Beijing, China
| | - Peng Wang
- Department of Neurosurgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yantao Zhao
- Senior Department of Orthopaedics, The Fourth Medical Center of PLA General Hospital, Beijing, China
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3
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Li Y, Li L, Li Y, Feng L, Wang B, Wang M, Wang H, Zhu M, Yang Y, Waldorff EI, Zhang N, Viohl I, Lin S, Bian L, Lee WYW, Li G. Enhancing cartilage repair with optimized supramolecular hydrogel-based scaffold and pulsed electromagnetic field. Bioact Mater 2023; 22:312-324. [PMID: 36263100 PMCID: PMC9576572 DOI: 10.1016/j.bioactmat.2022.10.010] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 10/05/2022] [Accepted: 10/05/2022] [Indexed: 11/05/2022] Open
Abstract
Functional tissue engineering strategies provide innovative approach for the repair and regeneration of damaged cartilage. Hydrogel is widely used because it could provide rapid defect filling and proper structure support, and is biocompatible for cell aggregation and matrix deposition. Efforts have been made to seek suitable scaffolds for cartilage tissue engineering. Here Alg-DA/Ac-β-CD/gelatin hydrogel was designed with the features of physical and chemical multiple crosslinking and self-healing properties. Gelation time, swelling ratio, biodegradability and biocompatibility of the hydrogels were systematically characterized, and the injectable self-healing adhesive hydrogel were demonstrated to exhibit ideal properties for cartilage repair. Furthermore, the new hydrogel design introduces a pre-gel state before photo-crosslinking, where increased viscosity and decreased fluidity allow the gel to remain in a semi-solid condition. This granted multiple administration routes to the hydrogels, which brings hydrogels the ability to adapt to complex clinical situations. Pulsed electromagnetic fields (PEMF) have been recognized as a promising solution to various health problems owing to their noninvasive properties and therapeutic potentials. PEMF treatment offers a better clinical outcome with fewer, if any, side effects, and wildly used in musculoskeletal tissue repair. Thereby we propose PEMF as an effective biophysical stimulation to be 4th key element in cartilage tissue engineering. In this study, the as-prepared Alg-DA/Ac-β-CD/gelatin hydrogels were utilized in the rat osteochondral defect model, and the potential application of PEMF in cartilage tissue engineering were investigated. PEMF treatment were proven to enhance the quality of engineered chondrogenic constructs in vitro, and facilitate chondrogenesis and cartilage repair in vivo. All of the results suggested that with the injectable self-healing adhesive hydrogel and PEMF treatment, this newly proposed tissue engineering strategy revealed superior clinical potential for cartilage defect treatment.
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Affiliation(s)
- Yucong Li
- Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong Special Administrative Region
| | - Linlong Li
- Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong Special Administrative Region
| | - Ye Li
- Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong Special Administrative Region
- Department of Rehabilitation Sciences, Hong Kong Polytechnic University, Hong Kong Special Administrative Region
| | - Lu Feng
- Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong Special Administrative Region
| | - Bin Wang
- Innovation Centre for Advanced Interdisciplinary Medicine, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Ming Wang
- Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong Special Administrative Region
| | - Haixing Wang
- Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong Special Administrative Region
| | - Meiling Zhu
- The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, PR China
| | - Yongkang Yang
- Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong Special Administrative Region
| | - Erik I. Waldorff
- Research & Clinical Affairs, Orthofix Medical Inc., Lewisville, TX, USA
| | - Nianli Zhang
- Research & Clinical Affairs, Orthofix Medical Inc., Lewisville, TX, USA
| | - Ingmar Viohl
- Research & Clinical Affairs, Orthofix Medical Inc., Lewisville, TX, USA
| | - Sien Lin
- Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong Special Administrative Region
| | - Liming Bian
- School of Biomedical Sciences and Engineering, National Engineering Research Center for Tissue Restoration and Reconstruction, Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou, PR China
| | - Wayne Yuk-Wai Lee
- Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong Special Administrative Region
- Department of Orthopaedics and Traumatology, SH Ho Scoliosis Research Laboratory, Joint Scoliosis Research Center of the Chinese University of Hong Kong and Nanjing University, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
| | - Gang Li
- Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong Special Administrative Region
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Liu X, Sun S, Wang N, Kang R, Xie L, Liu X. Therapeutic application of hydrogels for bone-related diseases. Front Bioeng Biotechnol 2022; 10:998988. [PMID: 36172014 PMCID: PMC9510597 DOI: 10.3389/fbioe.2022.998988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Accepted: 08/29/2022] [Indexed: 01/15/2023] Open
Abstract
Bone-related diseases caused by trauma, infection, and aging affect people’s health and quality of life. The prevalence of bone-related diseases has been increasing yearly in recent years. Mild bone diseases can still be treated with conservative drugs and can be cured confidently. However, serious bone injuries caused by large-scale trauma, fractures, bone tumors, and other diseases are challenging to heal on their own. Open surgery must be used for intervention. The treatment method also faces the problems of a long cycle, high cost, and serious side effects. Studies have found that hydrogels have attracted much attention due to their good biocompatibility and biodegradability and show great potential in treating bone-related diseases. This paper mainly introduces the properties and preparation methods of hydrogels, reviews the application of hydrogels in bone-related diseases (including bone defects, bone fracture, cartilage injuries, and osteosarcoma) in recent years. We also put forward suggestions according to the current development status, pointing out a new direction for developing high-performance hydrogels more suitable for bone-related diseases.
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Affiliation(s)
- Xiyu Liu
- Third School of Clinical Medicine, Nanjing University of Traditional Chinese Medicine, Nanjing, China
| | - Shuoshuo Sun
- Third School of Clinical Medicine, Nanjing University of Traditional Chinese Medicine, Nanjing, China
| | - Nan Wang
- Third School of Clinical Medicine, Nanjing University of Traditional Chinese Medicine, Nanjing, China
| | - Ran Kang
- Third School of Clinical Medicine, Nanjing University of Traditional Chinese Medicine, Nanjing, China
- Department of Orthopedics, Nanjing Lishui Hospital of Traditional Chinese Medicine, Nanjing, China
- *Correspondence: Ran Kang, ; Lin Xie, ; Xin Liu,
| | - Lin Xie
- Third School of Clinical Medicine, Nanjing University of Traditional Chinese Medicine, Nanjing, China
- *Correspondence: Ran Kang, ; Lin Xie, ; Xin Liu,
| | - Xin Liu
- Third School of Clinical Medicine, Nanjing University of Traditional Chinese Medicine, Nanjing, China
- Department of Orthopedics, Nanjing Lishui Hospital of Traditional Chinese Medicine, Nanjing, China
- *Correspondence: Ran Kang, ; Lin Xie, ; Xin Liu,
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5
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Barati M, Darvishi B, Javidi MA, Mohammadian A, Shariatpanahi SP, Eisavand MR, Madjid Ansari A. Cellular stress response to extremely low-frequency electromagnetic fields (ELF-EMF): An explanation for controversial effects of ELF-EMF on apoptosis. Cell Prolif 2021; 54:e13154. [PMID: 34741480 PMCID: PMC8666288 DOI: 10.1111/cpr.13154] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 09/21/2021] [Accepted: 10/12/2021] [Indexed: 12/12/2022] Open
Abstract
Impaired apoptosis is one of the hallmarks of cancer, and almost all of the non‐surgical approaches of eradicating tumour cells somehow promote induction of apoptosis. Indeed, numerous studies have stated that non‐ionizing non‐thermal extremely low‐frequency magnetic fields (ELF‐MF) can modulate the induction of apoptosis in exposed cells; however, much controversy exists in observations. When cells are exposed to ELF‐EMF alone, very low or no statistically significant changes in apoptosis are observed. Contrarily, exposure to ELF‐EMF in the presence of a co‐stressor, including a chemotherapeutic agent or ionizing radiation, can either potentiate or inhibit apoptotic effects of the co‐stressor. In our idea, the main point neglected in interpreting these discrepancies is “the cellular stress responses” of cells following ELF‐EMF exposure and its interplay with apoptosis. The main purpose of the current review was to outline the triangle of ELF‐EMF, the cellular stress response of cells and apoptosis and to interpret and unify discrepancies in results based on it. Therefore, initially, we will describe studies performed on identifying the effect of ELF‐EMF on induction/inhibition of apoptosis and enumerate proposed pathways through which ELF‐EMF exposure may affect apoptosis; then, we will explain cellular stress response and cues for its induction in response to ELF‐EMF exposure; and finally, we will explain why such controversies have been observed by different investigators.
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Affiliation(s)
- Mojdeh Barati
- Integrative Oncology Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran
| | - Behrad Darvishi
- Recombinant Proteins Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran
| | - Mohammad Amin Javidi
- Integrative Oncology Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran
| | - Ali Mohammadian
- Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | | | - Mohammad Reza Eisavand
- Recombinant Proteins Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran
| | - Alireza Madjid Ansari
- Integrative Oncology Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran
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6
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Gao L, Cucchiarini M, Madry H. Cyst formation in the subchondral bone following cartilage repair. Clin Transl Med 2020; 10:e248. [PMID: 33377663 PMCID: PMC7733665 DOI: 10.1002/ctm2.248] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2020] [Revised: 11/23/2020] [Accepted: 11/27/2020] [Indexed: 12/20/2022] Open
Abstract
Subchondral bone cysts represent an early postoperative sign associated with many articular cartilage repair procedures. They may be defined as an abnormal cavity within the subchondral bone in close proximity of a treated cartilage defect with a possible communication to the joint cavity in the absence of osteoarthritis. Two synergistic mechanisms of subchondral cyst formation, the theory of internal upregulation of local proinflammatory factors, and the external hydraulic theory, are proposed to explain their occurrence. This review describes subchondral bone cysts in the context of articular cartilage repair to improve investigations of these pathological changes. It summarizes their epidemiology in both preclinical and clinical settings with a focus on individual cartilage repair procedures, examines an algorithm for subchondral bone analysis, elaborates on the underlying mechanism of subchondral cyst formation, and condenses the clinical implications and perspectives on subchondral bone cyst formation in cartilage repair.
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Affiliation(s)
- Liang Gao
- Center of Experimental OrthopaedicsSaarland University Medical Center and Saarland UniversityHomburgGermany
| | - Magali Cucchiarini
- Center of Experimental OrthopaedicsSaarland University Medical Center and Saarland UniversityHomburgGermany
| | - Henning Madry
- Center of Experimental OrthopaedicsSaarland University Medical Center and Saarland UniversityHomburgGermany
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7
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Dai W, Sun M, Leng X, Hu X, Ao Y. Recent Progress in 3D Printing of Elastic and High-Strength Hydrogels for the Treatment of Osteochondral and Cartilage Diseases. Front Bioeng Biotechnol 2020; 8:604814. [PMID: 33330436 PMCID: PMC7729093 DOI: 10.3389/fbioe.2020.604814] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Accepted: 11/03/2020] [Indexed: 11/13/2022] Open
Abstract
Despite considerable progress for the regenerative medicine, repair of full-thickness articular cartilage defects and osteochondral interface remains challenging. This low efficiency is largely due to the difficulties in recapitulating the stratified zonal architecture of articular cartilage and engineering complex gradients for bone-soft tissue interface. This has led to increased interest in three-dimensional (3D) printing technologies in the field of musculoskeletal tissue engineering. Printable and biocompatible hydrogels are attractive materials for 3D printing applications because they not only own high tunability and complexity, but also offer favorable biomimetic environments for live cells, such as porous structure, high water content, and bioactive molecule incorporation. However, conventional hydrogels are usually mechanically weak and brittle, which cannot reach the mechanical requirements for repair of articular cartilage defects and osteochondral interface. Therefore, the development of elastic and high-strength hydrogels for 3D printing in the repairment of cartilage defects and osteochondral interface is crucial. In this review, we summarized the recent progress in elastic and high-strength hydrogels for 3D printing and categorized them into six groups, namely ion bonds interactions, nanocomposites integrated in hydrogels, supramolecular guest-host interactions, hydrogen bonds interactions, dynamic covalent bonds interactions, and hydrophobic interactions. These 3D printed elastic and high-strength hydrogels may provide new insights for the treatment of osteochondral and cartilage diseases.
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Affiliation(s)
- Wenli Dai
- Beijing Key Laboratory of Sports Injuries, Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Muyang Sun
- Beijing Key Laboratory of Sports Injuries, Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Xi Leng
- Medical Imaging Center, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xiaoqing Hu
- Beijing Key Laboratory of Sports Injuries, Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
| | - Yingfang Ao
- Beijing Key Laboratory of Sports Injuries, Institute of Sports Medicine, Peking University Third Hospital, Beijing, China
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8
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Lu Z, Zhou S, Vaida J, Gao G, Stewart A, Parenti J, Yan L, Pei M. Unfavorable Contribution of a Tissue-Engineering Cartilage Graft to Osteochondral Defect Repair in Young Rabbits. Front Cell Dev Biol 2020; 8:595518. [PMID: 33195273 PMCID: PMC7658375 DOI: 10.3389/fcell.2020.595518] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2020] [Accepted: 10/12/2020] [Indexed: 11/17/2022] Open
Abstract
A stem cell-based tissue-engineering approach is a promising strategy for treatment of cartilage defects. However, there are conflicting data in the feasibility of using this approach in young recipients. A young rabbit model with an average age of 7.7 months old was used to evaluate the effect of a tissue-engineering approach on the treatment of osteochondral defects. Following in vitro evaluation of proliferation and chondrogenic capacity of infrapatellar fat pad-derived stem cells (IPFSCs) after expansion on either tissue culture plastic (TCP) or decellularized extracellular matrix (dECM), a premature tissue construct engineered from pretreated IPFSCs was used to repair osteochondral defects in young rabbits. We found that dECM expanded IPFSCs exhibited higher proliferation and chondrogenic differentiation compared to TCP expanded cells in both pellet and tissue construct culture systems. Six weeks after creation of bilateral osteochondral defects in the femoral trochlear groove of rabbits, the Empty group (left untreated) had the best cartilage resurfacing with the highest score in Modified O’Driscoll Scale (MODS) than the other groups; however, this score had no significant difference compared to that of 15-week samples, indicating that young rabbits stop growing cartilage once they reach 9 months old. Interestingly, implantation of premature tissue constructs from both dECM and TCP groups exhibited significantly improved cartilage repair at 15 weeks compared to those at six weeks (about 9 months old), indicating that a tissue-engineering approach is able to repair adult cartilage defects. We also found that implanted pre-labeled cells in premature tissue constructs were undetectable in resurfaced cartilage at both time points. This study suggests that young rabbits (less than 9 months old) might respond differently to the classical tissue-engineering approach that is considered as a potential treatment for cartilage defects in adult rabbits.
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Affiliation(s)
- Zhihua Lu
- Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics, West Virginia University, Morgantown, WV, United States.,Department of Orthopedics, Clinical Medical College of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou, China
| | - Sheng Zhou
- Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics, West Virginia University, Morgantown, WV, United States
| | - Justin Vaida
- Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics, West Virginia University, Morgantown, WV, United States
| | - Gongming Gao
- Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics, West Virginia University, Morgantown, WV, United States
| | - Amanda Stewart
- Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics, West Virginia University, Morgantown, WV, United States
| | - Joshua Parenti
- Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics, West Virginia University, Morgantown, WV, United States
| | - Lianqi Yan
- Department of Orthopedics, Clinical Medical College of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou, China
| | - Ming Pei
- Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics, West Virginia University, Morgantown, WV, United States.,WVU Cancer Institute, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV, United States
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9
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Hu H, Yang W, Zeng Q, Chen W, Zhu Y, Liu W, Wang S, Wang B, Shao Z, Zhang Y. Promising application of Pulsed Electromagnetic Fields (PEMFs) in musculoskeletal disorders. Biomed Pharmacother 2020; 131:110767. [PMID: 33152929 DOI: 10.1016/j.biopha.2020.110767] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 09/06/2020] [Accepted: 09/17/2020] [Indexed: 12/13/2022] Open
Abstract
Increasing evidence suggests that an exogenous electromagnetic field might be involved in many biologic processes which are of great importance for therapeutic interventions. Pulsed electromagnetic fields (PEMFs) are known to be a noninvasive, safe and effective therapy agent without apparent side effects. Numerous studies have shown that PEMFs possess the potential to become a stand-alone or adjunctive treatment modality for treating musculoskeletal disorders. However, several issues remain unresolved. Prior to their widely clinical application, further researches from well-designed, high-quality studies are still required to standardize the treatment parameters and derive the optimal protocol for health-care decision making. In this review, we aim to provide current evidence on the mechanism of action, clinical applications, and controversies of PEMFs in musculoskeletal disorders.
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Affiliation(s)
- Hongzhi Hu
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China.
| | - Wenbo Yang
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
| | - Qianwen Zeng
- Department of Pediatrics, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China.
| | - Wei Chen
- Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China
| | - YanBin Zhu
- Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China
| | - Weijian Liu
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Shangyu Wang
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Baichuan Wang
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
| | - Zengwu Shao
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
| | - Yingze Zhang
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China.
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10
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Desai S, Jayasuriya CT. Implementation of Endogenous and Exogenous Mesenchymal Progenitor Cells for Skeletal Tissue Regeneration and Repair. Bioengineering (Basel) 2020; 7:E86. [PMID: 32759659 PMCID: PMC7552784 DOI: 10.3390/bioengineering7030086] [Citation(s) in RCA: 9] [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: 06/21/2020] [Revised: 07/25/2020] [Accepted: 07/30/2020] [Indexed: 02/06/2023] Open
Abstract
Harnessing adult mesenchymal stem/progenitor cells to stimulate skeletal tissue repair is a strategy that is being actively investigated. While scientists continue to develop creative and thoughtful ways to utilize these cells for tissue repair, the vast majority of these methodologies can ultimately be categorized into two main approaches: (1) Facilitating the recruitment of endogenous host cells to the injury site; and (2) physically administering into the injury site cells themselves, exogenously, either by autologous or allogeneic implantation. The aim of this paper is to comprehensively review recent key literature on the use of these two approaches in stimulating healing and repair of different skeletal tissues. As expected, each of the two strategies have their own advantages and limitations (which we describe), especially when considering the diverse microenvironments of different skeletal tissues like bone, tendon/ligament, and cartilage/fibrocartilage. This paper also discusses stem/progenitor cells commonly used for repairing different skeletal tissues, and it lists ongoing clinical trials that have risen from the implementation of these cells and strategies. Lastly, we discuss our own thoughts on where the field is headed in the near future.
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Affiliation(s)
| | - Chathuraka T. Jayasuriya
- Department of Orthopaedics, Warren Alpert Medical School of Brown University and the Rhode Island Hospital, Providence, RI 02903, USA;
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11
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Tsai CC, Kuo SH, Lu TY, Cheng NC, Shie MY, Yu J. Enzyme-Cross-linked Gelatin Hydrogel Enriched with an Articular Cartilage Extracellular Matrix and Human Adipose-Derived Stem Cells for Hyaline Cartilage Regeneration of Rabbits. ACS Biomater Sci Eng 2020; 6:5110-5119. [PMID: 33455262 DOI: 10.1021/acsbiomaterials.9b01756] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Hyaline cartilage regeneration remains clinically challenging. In this study, microbial transglutaminase was used to cross-link gelatin. The articular cartilage extracellular matrix (cECM), mainly comprising collagen type II and glycosaminoglycans (GAGs), which can support chondrogenesis, was enclosed in this enzyme-catalyzed hydrogel. After human adipose-derived stem cells (hASCs) were encapsulated in the hydrogel enriched with the cECM, the results demonstrated that the enzymatic cross-linking reaction is of low cytotoxicity. Moreover, the stem cells showed great proliferation and chondrogenic differentiation potential in the hydrogel. Most importantly, we assessed the therapeutic effects of applying a hydrogel enriched with the cECM and hASCs to repair a full-thickness osteochondral defect. At 8 weeks after surgery, the GCC group (hydrogel encapsulating cells and the cECM) exhibited a smooth articular surface with transparent new hyaline-like tissue macroscopically. According to histological analysis, inflammatory responses were hardly observed, and sound chondrocytes were aligned in the newly formed chondral layer. In addition, the GCC group exhibited significant improvement in the GAG content between weeks 4 and 8. In summary, the implantation of a gelatin hydrogel enriched with the cECM and hASCs could facilitate the hyaline cartilage regeneration significantly in rabbit knee joint models.
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Affiliation(s)
- Ching-Cheng Tsai
- Department of Chemical Engineering, National Taiwan University, No.1, Sec. 4, Roosevelt Rd., Da'an Dist., Taipei City 10617, Taiwan
| | - Shuo-Hsiu Kuo
- Department of Chemical Engineering, National Taiwan University, No.1, Sec. 4, Roosevelt Rd., Da'an Dist., Taipei City 10617, Taiwan
| | - Ting-Yu Lu
- Department of Chemical Engineering, National Taiwan University, No.1, Sec. 4, Roosevelt Rd., Da'an Dist., Taipei City 10617, Taiwan
| | - Nai-Chen Cheng
- Department of Surgery, National Taiwan University Hospital, No.1, Changde St., Zhongzheng Dist., Taipei City 10048, Taiwan
| | - Ming-You Shie
- Department of Dentistry, China Medical University, No.91 Hsueh-Shih Rd., Taichung City 40402, Taiwan
| | - Jiashing Yu
- Department of Chemical Engineering, National Taiwan University, No.1, Sec. 4, Roosevelt Rd., Da'an Dist., Taipei City 10617, Taiwan
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Lullini G, Cammisa E, Setti S, Sassoli I, Zaffagnini S, Marcheggiani Muccioli GM. Role of pulsed electromagnetic fields after joint replacements. World J Orthop 2020; 11:285-293. [PMID: 32572365 PMCID: PMC7298453 DOI: 10.5312/wjo.v11.i6.285] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Revised: 05/14/2020] [Accepted: 05/28/2020] [Indexed: 02/06/2023] Open
Abstract
Although the rate of patients reporting satisfaction is generally high after joint replacement surgery, up to 23% after total hip replacement and 34% after total knee arthroplasty of treated subjects report discomfort or pain 1 year after surgery. Moreover, chronic or subacute inflammation is reported in some cases even a long time after surgery. Another open and debated issue in prosthetic surgery is implant survivorship, especially when related to good prosthesis bone ingrowth. Pulsed Electro Magnetic Fields (PEMFs) treatment, although initially recommended after total joint replacement to promote bone ingrowth and to reduce inflammation and pain, is not currently part of usual clinical practice. The purpose of this review was to analyze existing literature on PEMFs effects in joint replacement surgery and to report results of clinical studies and current indications. We selected all currently available prospective studies or RCT on the use of PEMFs in total joint replacement with the purpose of investigating effects of PEMFs on recovery, pain relief and patients’ satisfaction following hip, knee or shoulder arthroplasty. All the studies analyzed reported no adverse effects, and good patient compliance to the treatment. The available literature shows that early control of joint inflammation process in the first days after surgery through the use of PEMFs should be considered an effective completion of the surgical procedure to improve the patient’s functional recovery.
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Affiliation(s)
- Giada Lullini
- Laboratorio di Analisi del Movimento e di valutazione funzionale protesi, IRCCS Istituto Ortopedico Rizzoli - DIBINEM - University of Bologna, Bologna 40100, Italy
| | - Eugenio Cammisa
- II Orthopaedic and Traumatology Clinic, IRCCS Istituto Ortopedico Rizzoli - DIBINEM - University of Bologna, Bologna 40100, Italy
| | - Stefania Setti
- Laboratory of Clinical Biophysics, IGEA S.p.A. Clinical Biophysics, 41012 Carpi (Mo), Italy
| | - Iacopo Sassoli
- II Orthopaedic and Traumatology Clinic, IRCCS Istituto Ortopedico Rizzoli - DIBINEM - University of Bologna, Bologna 40100, Italy
| | - Stefano Zaffagnini
- II Orthopaedic and Traumatology Clinic, IRCCS Istituto Ortopedico Rizzoli - DIBINEM - University of Bologna, Bologna 40100, Italy
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13
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Stefani RM, Barbosa S, Tan AR, Setti S, Stoker AM, Ateshian GA, Cadossi R, Vunjak-Novakovic G, Aaron RK, Cook JL, Bulinski JC, Hung CT. Pulsed electromagnetic fields promote repair of focal articular cartilage defects with engineered osteochondral constructs. Biotechnol Bioeng 2020; 117:1584-1596. [PMID: 31985051 PMCID: PMC8845061 DOI: 10.1002/bit.27287] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Revised: 12/14/2019] [Accepted: 01/24/2020] [Indexed: 12/13/2022]
Abstract
Articular cartilage injuries are a common source of joint pain and dysfunction. We hypothesized that pulsed electromagnetic fields (PEMFs) would improve growth and healing of tissue-engineered cartilage grafts in a direction-dependent manner. PEMF stimulation of engineered cartilage constructs was first evaluated in vitro using passaged adult canine chondrocytes embedded in an agarose hydrogel scaffold. PEMF coils oriented parallel to the articular surface induced superior repair stiffness compared to both perpendicular PEMF (p = .026) and control (p = .012). This was correlated with increased glycosaminoglycan deposition in both parallel and perpendicular PEMF orientations compared to control (p = .010 and .028, respectively). Following in vitro optimization, the potential clinical translation of PEMF was evaluated in a preliminary in vivo preclinical adult canine model. Engineered osteochondral constructs (∅ 6 mm × 6 mm thick, devitalized bone base) were cultured to maturity and implanted into focal defects created in the stifle (knee) joint. To assess expedited early repair, animals were assessed after a 3-month recovery period, with microfracture repairs serving as an additional clinical control. In vivo, PEMF led to a greater likelihood of normal chondrocyte (odds ratio [OR]: 2.5, p = .051) and proteoglycan (OR: 5.0, p = .013) histological scores in engineered constructs. Interestingly, engineered constructs outperformed microfracture in clinical scoring, regardless of PEMF treatment (p < .05). Overall, the studies provided evidence that PEMF stimulation enhanced engineered cartilage growth and repair, demonstrating a potential low-cost, low-risk, noninvasive treatment modality for expediting early cartilage repair.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Clark T. Hung
- Columbia University, New York, NY
- Clark T. Hung, 351 Engineering Terrace Building, Mail Code 8904, 1210 Amsterdam Avenue, New York, NY 10027, Tel: (212) 854-6542, Fax: (212) 854-8725,
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Ye W, Guo H, Yang X, Yang L, He C. Pulsed Electromagnetic Field Versus Whole Body Vibration on Cartilage and Subchondral Trabecular Bone in Mice With Knee Osteoarthritis. Bioelectromagnetics 2020; 41:298-307. [PMID: 32277513 DOI: 10.1002/bem.22263] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Revised: 01/17/2020] [Accepted: 03/29/2020] [Indexed: 02/05/2023]
Abstract
Pulsed electromagnetic field (PEMF) and whole body vibration (WBV) interventions are expected to be important strategies for management of osteoarthritis (OA). The aim of the study was to investigate the comparative effectiveness of PEMF versus WBV on cartilage and subchondral trabecular bone in mice with knee OA (KOA) induced by surgical destabilization of the medial meniscus (DMM). Forty 12-week-old male C57/BL mice were randomly divided into four groups (n = 10): Control, OA, PEMF, and WBV. OA was induced (OA, PEMF, and WBV groups) by surgical DMM of right knee joint. Mice in PEMF group received 1 h/day PEMF exposure with 75 Hz, 1.6 mT for 4 weeks, and the WBV group was exposed to WBV for 20 min/day with 5 Hz, 4 mm, 0.3 g peak acceleration for 4 weeks. Micro-computed tomography (micro-CT), histology, and immunohistochemistry analyses were performed to evaluate the changes in cartilage and microstructure of trabecular bone. The bone volume fraction (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) increased, and bone surface/bone volume (BS/BV) decreased by micro-CT analysis in PEMF and WBV groups. The Osteoarthritis Research Society International (OARSI) scores in PEMF and WBV groups were significantly lower than in the OA group. Immunohistochemical results showed that PEMF and WBV promoted expressions of Aggrecan, and inhibited expressions of IL-1β, ADAMTS4, and MMP13. Superior results are seen in PEMF group compared with WBV group. Both PEMF and WBV were effective, could delay cartilage degeneration and preserve subchondral trabecular bone microarchitecture, and PEMF was found to be superior to WBV. Bioelectromagnetics. 2020;41:298-307 © 2020 Bioelectromagnetics Society.
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Affiliation(s)
- Wenwen Ye
- Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, People's Republic of China
- School of Rehabilitation Sciences, West China School of Medicine, Sichuan University, Chengdu, People's Republic of China
- Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Hua Guo
- Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, People's Republic of China
- School of Rehabilitation Sciences, West China School of Medicine, Sichuan University, Chengdu, People's Republic of China
- Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Xiaotian Yang
- Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, People's Republic of China
- School of Rehabilitation Sciences, West China School of Medicine, Sichuan University, Chengdu, People's Republic of China
- Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Lin Yang
- Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, People's Republic of China
- School of Rehabilitation Sciences, West China School of Medicine, Sichuan University, Chengdu, People's Republic of China
- Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Chengqi He
- Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, People's Republic of China
- School of Rehabilitation Sciences, West China School of Medicine, Sichuan University, Chengdu, People's Republic of China
- Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, People's Republic of China
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Bao W, Li M, Yang Y, Wan Y, Wang X, Bi N, Li C. Advancements and Frontiers in the High Performance of Natural Hydrogels for Cartilage Tissue Engineering. Front Chem 2020; 8:53. [PMID: 32117879 PMCID: PMC7028759 DOI: 10.3389/fchem.2020.00053] [Citation(s) in RCA: 81] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2019] [Accepted: 01/17/2020] [Indexed: 12/14/2022] Open
Abstract
Cartilage injury originating from trauma or osteoarthritis is a common joint disease that can bring about an increasing social and economic burden in modern society. On account of its avascular, neural, and lymphatic characteristics, the poor migration ability of chondrocytes, and a low number of progenitor cells, the self-healing ability of cartilage defects has been significantly limited. Natural hydrogels, occurring abundantly with characteristics such as high water absorption, biodegradation, adjustable porosity, and biocompatibility like that of the natural extracellular matrix (ECM), have been developed into one of the most suitable scaffold biomaterials for the regeneration of cartilage in material science and tissue engineering. Notably, natural hydrogels derived from sources such as animal or human cadaver tissues possess the bionic mechanical behaviors of physiological cartilage that are required for usage as articular cartilage substitutes, by which the enhanced chondrogenic phenotype ability may be achieved by facilely embedding living cells, controlling degradation profiles, and releasing stimulatory growth factors. Hence, we summarize an overview of strategies and developments of the various kinds and functions of natural hydrogels for cartilage tissue engineering in this review. The main concepts and recent essential research found that great challenges like vascularity, clinically relevant size, and mechanical performances were still difficult to overcome because the current limitations of technologies need to be severely addressed in practical settings, particularly in unpredictable preclinical trials and during future forays into cartilage regeneration using natural hydrogel scaffolds with high mechanical properties. Therefore, the grand aim of this current review is to underpin the importance of preparation, modification, and application for the high performance of natural hydrogels for cartilage tissue engineering, which has been achieved by presenting a promising avenue in various fields and postulating real-world respective potentials.
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Affiliation(s)
- Wuren Bao
- School of Nursing, Inner Mongolia University for Nationalities, Tongliao, China
| | - Menglu Li
- Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics & Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China
| | - Yanyu Yang
- Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics & Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China
- College of Science and Engineering, Zhengzhou University, Zhengzhou, China
| | - Yi Wan
- Orthopaedic Department, The 8th Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Xing Wang
- Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics & Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Na Bi
- Orthopaedic Department, The 8th Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Chunlin Li
- Orthopaedic Department, The 8th Medical Center of Chinese PLA General Hospital, Beijing, China
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Zheng L, Li D, Wang W, Zhang Q, Zhou X, Liu D, Zhang J, You Z, Zhang J, He C. Bilayered Scaffold Prepared from a Kartogenin-Loaded Hydrogel and BMP-2-Derived Peptide-Loaded Porous Nanofibrous Scaffold for Osteochondral Defect Repair. ACS Biomater Sci Eng 2019; 5:4564-4573. [PMID: 33448830 DOI: 10.1021/acsbiomaterials.9b00513] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Recently, a bilayered scaffold with an anisotropic structure mimicking a native osteochondral tissue shows considerable potential for treating osteochondral defects. Herein, a bilayered scaffold consisting of biomimetic cartilage and a subchondral bone architecture was constructed for repairing osteochondral defect. A hydrogel prepared by the Schiff base reaction of gelatin, silk fibroin, and oxidized dextran was designed as the cartilage layer, while a nanofibrous scaffold with a macroporous structure prepared from the polymer blend of poly(l-lactic acid)/poly(lactic-co-glycolic acid)/poly(ε-caprolactone) using the dual phase separation technique served as a subchondral layer. The subchondral layer was then treated with polydopamine coating for osteogenic factor immobilization. To facilitate the chondrogenic and osteogenic differentiation of bone marrow mesenchymal stem cells on the bilayered scaffold, the cartilage-inducing drug kartogenin (KGN) and osteogenic-inducing factor bone morphogenetic protein 2-derived peptides (P24 peptides) were, respectively, loaded on the subchondral layer. Next, the in vitro release of KGN and P24 peptide from the corresponding layer was monitored, respectively, and the results showed that both the release time of KGN and P24 peptides would last for more than 28 days. The in vitro results indicated that the KGN-loaded cartilage layer and P24 peptides-loaded subchondral layer were capable of supporting cell proliferation, and induced the chondrogenic and osteogenic differentiation, respectively. Furthermore, the in vivo experiments suggested that the bilayered scaffold significantly accelerated the regeneration of the osteochondral tissue in the rabbit knee joint model. Consequently, this bilayered scaffold loaded with KGN and P24 peptides would be a promising candidate for repairing osteochondral defect.
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Affiliation(s)
| | - Dejian Li
- Department of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201301, China
| | | | | | | | | | | | | | - Jundong Zhang
- Tenth People's Hospital Affiliated to Tongji University, Shanghai 200072, China
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Signaling pathways involved in anti-inflammatory effects of Pulsed Electromagnetic Field in microglial cells. Cytokine 2019; 125:154777. [PMID: 31400640 DOI: 10.1016/j.cyto.2019.154777] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Revised: 06/14/2019] [Accepted: 07/09/2019] [Indexed: 11/27/2022]
Abstract
Literature studies suggest important protective effects of low-frequency, low-energy pulsed electromagnetic fields (PEMFs) on inflammatory pathways affecting joint and cerebral diseases. However, it is not clear on which bases they affect neuroprotection and the mechanism responsible is yet unknown. Therefore the aim of this study was to identify the molecular targets of PEMFs anti-neuroinflammatory action. The effects of PEMF exposure in cytokine production by lipopolysaccharide (LPS)-activated N9 microglial cells as well as the pathways involved, including adenylyl cyclase (AC), phospholipase C (PLC), protein kinase C epsilon (PKC-ε) and delta (PKC-δ), p38, ERK1/2, JNK1/2 mitogen activated protein kinases (MAPK), Akt and caspase 1, were investigated. In addition, the ability of PEMFs to modulate ROS generation, cell invasion and phagocytosis, was addressed. PEMFs reduced the LPS-increased production of TNF-α and IL-1β in N9 cells, through a pathway involving JNK1/2. Furthermore, they decreased the LPS-induced release of IL-6, by a mechanism not dependent on AC, PLC, PKC-ε, PKC-δ, p38, ERK1/2, JNK1/2, Akt and caspase 1. Importantly, a significant effect of PEMFs in the reduction of crucial cell functions specific of microglia like ROS generation, cell invasion and phagocytosis was found. PEMFs inhibit neuroinflammation in N9 cells through a mechanism involving, at least in part, the activation of JNK MAPK signalling pathway and may be relevant to treat a variety of diseases characterized by neuroinflammation.
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18
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Electrical stimulation-based bone fracture treatment, if it works so well why do not more surgeons use it? Eur J Trauma Emerg Surg 2019; 46:245-264. [PMID: 30955053 DOI: 10.1007/s00068-019-01127-z] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2018] [Accepted: 03/29/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND Electrical stimulation (EStim) has been proven to promote bone healing in experimental settings and has been used clinically for many years and yet it has not become a mainstream clinical treatment. METHODS To better understand this discrepancy we reviewed 72 animal and 69 clinical studies published between 1978 and 2017, and separately asked 161 orthopedic surgeons worldwide about their awareness, experience, and acceptance of EStim for treating fracture patients. RESULTS Of the 72 animal studies, 77% reported positive outcomes, and the most common model, bone, fracture type, and method of administering EStim were dog, tibia, large bone defects, and DC, respectively. Of the 69 clinical studies, 73% reported positive outcomes, and the most common bone treated, fracture type, and method of administration were tibia, delayed/non-unions, and PEMF, respectively. Of the 161 survey respondents, most (73%) were aware of the positive outcomes reported in the literature, yet only 32% used EStim in their patients. The most common fracture they treated was delayed/non-unions, and the greatest problems with EStim were high costs and inconsistent results. CONCLUSION Despite their awareness of EStim's pro-fracture healing effects few orthopedic surgeons use it in their patients. Our review of the literature and survey indicate that this is due to confusion in the literature due to the great variation in methods reported, and the inconsistent results associated with this treatment approach. In spite of this surgeons seem to be open to using this treatment if advancements in the technology were able to provide an easy to use, cost-effective method to deliver EStim in their fracture patients.
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Massari L, Benazzo F, Falez F, Perugia D, Pietrogrande L, Setti S, Osti R, Vaienti E, Ruosi C, Cadossi R. Biophysical stimulation of bone and cartilage: state of the art and future perspectives. INTERNATIONAL ORTHOPAEDICS 2019; 43:539-551. [PMID: 30645684 PMCID: PMC6399199 DOI: 10.1007/s00264-018-4274-3] [Citation(s) in RCA: 73] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Accepted: 12/03/2018] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Biophysical stimulation is a non-invasive therapy used in orthopaedic practice to increase and enhance reparative and anabolic activities of tissue. METHODS A sistematic web-based search for papers was conducted using the following titles: (1) pulsed electromagnetic field (PEMF), capacitively coupled electrical field (CCEF), low intensity pulsed ultrasound system (LIPUS) and biophysical stimulation; (2) bone cells, bone tissue, fracture, non-union, prosthesis and vertebral fracture; and (3) chondrocyte, synoviocytes, joint chondroprotection, arthroscopy and knee arthroplasty. RESULTS Pre-clinical studies have shown that the site of interaction of biophysical stimuli is the cell membrane. Its effect on bone tissue is to increase proliferation, synthesis and release of growth factors. On articular cells, it creates a strong A2A and A3 adenosine-agonist effect inducing an anti-inflammatory and chondroprotective result. In treated animals, it has been shown that the mineralisation rate of newly formed bone is almost doubled, the progression of the osteoarthritic cartilage degeneration is inhibited and quality of cartilage is preserved. Biophysical stimulation has been used in the clinical setting to promote the healing of fractures and non-unions. It has been successfully used on joint pathologies for its beneficial effect on improving function in early OA and after knee surgery to limit the inflammation of periarticular tissues. DISCUSSION The pooled result of the studies in this review revealed the efficacy of biophysical stimulation for bone healing and joint chondroprotection based on proven methodological quality. CONCLUSION The orthopaedic community has played a central role in the development and understanding of the importance of the physical stimuli. Biophysical stimulation requires care and precision in use if it is to ensure the success expected of it by physicians and patients.
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Affiliation(s)
- Leo Massari
- University of Ferrara, Via Vigne 4, 44121, Ferrara, Italy.
| | - Franco Benazzo
- IRCCS Foundation "San Matteo" Hospital, University of Pavia, 27100, Pavia, Italy
| | | | | | | | | | | | | | - Carlo Ruosi
- Federico II University Naples, 80100, Naples, Italy
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Maglio M, Tschon M, Sicuro L, Lolli R, Fini M. Osteochondral tissue cultures: Between limits and sparks, the next step for advanced in vitro models. J Cell Physiol 2018; 234:5420-5435. [DOI: 10.1002/jcp.27457] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Accepted: 08/29/2018] [Indexed: 01/01/2023]
Affiliation(s)
- Melania Maglio
- Laboratory of Preclinical and Surgical Studies, Rizzoli RIT Department IRCCS Rizzoli Orthopaedic Institute Bologna Italy
| | - Matilde Tschon
- Laboratory of Preclinical and Surgical Studies, Rizzoli RIT Department IRCCS Rizzoli Orthopaedic Institute Bologna Italy
| | - Laura Sicuro
- Laboratory of Preclinical and Surgical Studies, Rizzoli RIT Department IRCCS Rizzoli Orthopaedic Institute Bologna Italy
| | - Roberta Lolli
- Laboratory of Preclinical and Surgical Studies, Rizzoli RIT Department IRCCS Rizzoli Orthopaedic Institute Bologna Italy
| | - Milena Fini
- Laboratory of Biomechanics and Technology Innovation IRCCS IRCCS Rizzoli Orthopaedic Institute Bologna Italy
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21
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Kim YM, Lim HM, Ro HS, Ki GE, Seo YK. Pulsed Electromagnetic Fields Increase Pigmentation through the p-ERK/p-p38 Pathway in Zebrafish ( Danio rerio). Int J Mol Sci 2018; 19:E3211. [PMID: 30336610 PMCID: PMC6214121 DOI: 10.3390/ijms19103211] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Revised: 10/15/2018] [Accepted: 10/15/2018] [Indexed: 12/16/2022] Open
Abstract
Melanogenesis is a biological process resulting in the production of melanin pigment, which plays an important role in the prevention of sun-induced skin injury, and determines hair and skin color. So, a wide variety of approaches have been proposed to increase the synthesis of melanin. This study evaluated the effects of pulsed electromagnetic fields (PEMFs) on the pigmentation of zebrafish (Danio rerio) in vivo. We stimulated pigmentation in zebrafish by using specific frequencies and intensities of PEMFs. This study focuses on pigmentation using PEMFs, and finds that PEMFs, at an optimal intensity and frequency, upregulate pigmentation by the stimulated expression of tyrosinase-related protein 1 (TRP1), dopachrome tautomerase (DCT) through extracellular signal-regulated kinase(ERK) phosphorylation, and p38 phosphorylation signaling pathways in zebrafish. These results suggest that PEMFs, at an optimal intensity and frequency, are a useful tool in treating gray hair, with reduced melanin synthesis in the hair shaft or hypopigmentation-related skin disorders.
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Affiliation(s)
- Yu-Mi Kim
- Department of Medical Biotechnology (BK21 Plus Team), Dongguk University, Goyang-si 10326, Korea.
| | - Han-Moi Lim
- Department of Medical Biotechnology (BK21 Plus Team), Dongguk University, Goyang-si 10326, Korea.
| | | | - Ga-Eun Ki
- Department of Medical Biotechnology (BK21 Plus Team), Dongguk University, Goyang-si 10326, Korea.
| | - Young-Kwon Seo
- Department of Medical Biotechnology (BK21 Plus Team), Dongguk University, Goyang-si 10326, Korea.
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Rouabhia M, Mighri N, Mao J, Park HJ, Mighri F, Ajji A, Zhang Z. Surface treatment with amino acids of porous collagen based scaffolds to improve cell adhesion and proliferation. CAN J CHEM ENG 2018. [DOI: 10.1002/cjce.23205] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- Mahmoud Rouabhia
- Groupe de Recherche en Écologie Buccale; Faculté de Médecine Dentaire; Université Laval; 2420 rue de la Terrasse Québec QC G1V 0A6 Canada
| | - Nabila Mighri
- Groupe de Recherche en Écologie Buccale; Faculté de Médecine Dentaire; Université Laval; 2420 rue de la Terrasse Québec QC G1V 0A6 Canada
- Axe Médecine régénératrice; Centre de Recherche du CHU de Québec; Département de Chirurgie; Faculté de Médecine; Université Laval; Québec QC G1L 3L5 Canada
| | - Jifu Mao
- Axe Médecine régénératrice; Centre de Recherche du CHU de Québec; Département de Chirurgie; Faculté de Médecine; Université Laval; Québec QC G1L 3L5 Canada
| | - Hyun Jin Park
- Groupe de Recherche en Écologie Buccale; Faculté de Médecine Dentaire; Université Laval; 2420 rue de la Terrasse Québec QC G1V 0A6 Canada
- Axe Médecine régénératrice; Centre de Recherche du CHU de Québec; Département de Chirurgie; Faculté de Médecine; Université Laval; Québec QC G1L 3L5 Canada
| | - Frej Mighri
- Department of Chemical Engineering; Université Laval; 1065 avenue de la Médecine Québec QC G1V 0A6 Canada
| | - Abdallah Ajji
- Department of Chemical Engineering; École Polytechnique de Montréal; Montréal QC H3C 3A7 Canada
| | - Ze Zhang
- Axe Médecine régénératrice; Centre de Recherche du CHU de Québec; Département de Chirurgie; Faculté de Médecine; Université Laval; Québec QC G1L 3L5 Canada
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Collarile M, Sambri A, Lullini G, Cadossi M, Zorzi C. Biophysical stimulation improves clinical results of matrix-assisted autologous chondrocyte implantation in the treatment of chondral lesions of the knee. Knee Surg Sports Traumatol Arthrosc 2018. [PMID: 28624853 DOI: 10.1007/s00167-017-4605-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
PURPOSE The purpose of the present study was to evaluate the effects of pulsed electromagnetic fields (PEMFs) on clinical outcome in patients who underwent arthroscopic matrix-assisted autologous chondrocyte implantation (MACI) for chondral lesions of the knee. METHODS Thirty patients affected by grade III and IV International Cartilage Repair Society chondral lesions of the knee underwent MACI. After surgery, patients were randomly assigned to either experimental group (PEMFs 4 h per day for 60 days) or control group . Clinical outcome was evaluated through International Knee Documentation Committee (IKDC) subjective knee evaluation form, Visual Analog Scale, Short Form-36 (SF-36) and EuroQoL before surgery and 1, 2, 6, and 60 months postoperative. RESULTS Mean size of chondral lesion was 2.4 ± 0.6 cm2 in the PEMFs group and 2.5 ± 0.5 cm2 in the control one. No differences were found between groups at baseline. IKDC score increased in both groups till 6 months, but afterward improvement was observed only in the experimental group with a significant difference between groups at 60 months (p = 0.001). A significant difference between groups was recorded at 60 months for SF-36 (p = 0.006) and EuroQol (p = 0.020). A significant pain reduction was observed in the experimental group at 1-, 2- and 60-month follow-up. CONCLUSION Biophysical stimulation with PEMFs improves clinical outcome after arthroscopic MACI for chondral lesions of the knee in the short- and long-term follow-up. Biophysical stimulation should be considered as an effective tool in order to ameliorate clinical results of regenerative medicine. The use of PEMFs represents an innovative therapeutic approach for the survival of cartilage-engineered constructs and consequently the success of orthopaedic surgery. LEVEL OF EVIDENCE II.
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Affiliation(s)
- Marco Collarile
- Ospedale Sacro Cuore Don Calabria, Via Don Sempreboni 5, 37024, Negrar, VR, Italy
| | - Andrea Sambri
- Istituto Ortopedico Rizzoli, Via Cesare Pupilli 1, 40136, Bologna, Italy.
| | - Giada Lullini
- Istituto Ortopedico Rizzoli, Via Cesare Pupilli 1, 40136, Bologna, Italy
| | - Matteo Cadossi
- Istituto Ortopedico Rizzoli, Via Cesare Pupilli 1, 40136, Bologna, Italy
| | - Claudio Zorzi
- Ospedale Sacro Cuore Don Calabria, Via Don Sempreboni 5, 37024, Negrar, VR, Italy
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Tribe HC, McEwan J, Taylor H, Oreffo ROC, Tare RS. Mesenchymal Stem Cells: Potential Role in the Treatment of Osteochondral Lesions of the Ankle. Biotechnol J 2017; 12:1700070. [PMID: 29068173 PMCID: PMC5765412 DOI: 10.1002/biot.201700070] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Revised: 10/13/2017] [Indexed: 12/11/2022]
Abstract
Given articular cartilage has a limited repair potential, untreated osteochondral lesions of the ankle can lead to debilitating symptoms and joint deterioration necessitating joint replacement. While a wide range of reparative and restorative surgical techniques have been developed to treat osteochondral lesions of the ankle, there is no consensus in the literature regarding which is the ideal treatment. Tissue engineering strategies, encompassing stem cells, somatic cells, biomaterials, and stimulatory signals (biological and mechanical), have a potentially valuable role in the treatment of osteochondral lesions. Mesenchymal stem cells (MSCs) are an attractive resource for regenerative medicine approaches, given their ability to self-renew and differentiate into multiple stromal cell types, including chondrocytes. Although MSCs have demonstrated significant promise in in vitro and in vivo preclinical studies, their success in treating osteochondral lesions of the ankle is inconsistent, necessitating further clinical trials to validate their application. This review highlights the role of MSCs in cartilage regeneration and how the application of biomaterials and stimulatory signals can enhance chondrogenesis. The current treatments for osteochondral lesions of the ankle using regenerative medicine strategies are reviewed to provide a clinical context. The challenges for cartilage regeneration, along with potential solutions and safety concerns are also discussed.
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Affiliation(s)
- Howard C. Tribe
- Bone and Joint Research Group, Centre for Human Development, Stem Cells and RegenerationFaculty of MedicineUniversity of SouthamptonSouthamptonSO16 6YDUK
- Foot and Ankle Orthopaedic DepartmentRoyal Bournemouth HospitalBournemouthBH7 7DWUK
| | - Josephine McEwan
- Bone and Joint Research Group, Centre for Human Development, Stem Cells and RegenerationFaculty of MedicineUniversity of SouthamptonSouthamptonSO16 6YDUK
| | - Heath Taylor
- Foot and Ankle Orthopaedic DepartmentRoyal Bournemouth HospitalBournemouthBH7 7DWUK
| | - Richard O. C. Oreffo
- Bone and Joint Research Group, Centre for Human Development, Stem Cells and RegenerationFaculty of MedicineUniversity of SouthamptonSouthamptonSO16 6YDUK
| | - Rahul S. Tare
- Bone and Joint Research Group, Centre for Human Development, Stem Cells and RegenerationFaculty of MedicineUniversity of SouthamptonSouthamptonSO16 6YDUK
- Bioengineering Science, Mechanical Engineering DepartmentFaculty of Engineering and the EnvironmentUniversity of SouthamptonSouthamptonSO17 1BJUK
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Iwasa K, Reddi AH. Pulsed Electromagnetic Fields and Tissue Engineering of the Joints. TISSUE ENGINEERING PART B-REVIEWS 2017; 24:144-154. [PMID: 29020880 DOI: 10.1089/ten.teb.2017.0294] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Bone and joint formation, maintenance, and regeneration are regulated by both chemical and physical signals. Among the physical signals there is an increasing realization of the role of pulsed electromagnetic fields (PEMF) in the treatment of nonunions of bone fractures. The discovery of the piezoelectric properties of bone by Fukada and Yasuda in 1953 in Japan established the foundation of this field. Pioneering research by Bassett and Brighton and their teams resulted in the approval by the Food and Drug Administration (FDA) of the use of PEMF in the treatment of fracture healing. Although PEMF has potential applications in joint regeneration in osteoarthritis (OA), this evolving field is still in its infancy and offers novel opportunities. METHODS We have systematically reviewed the literature on the influence of PEMF in joints, including articular cartilage, tendons, and ligaments, of publications from 2000 to 2016. CONCLUSIONS PEMF stimulated chondrocyte proliferation, differentiation, and extracellular matrix synthesis by release of anabolic morphogens such as bone morphogenetic proteins and anti-inflammatory cytokines by adenosine receptors A2A and A3 in both in vitro and in vivo investigations. It is noteworthy that in clinical translational investigations a beneficial effect was observed on improving function in OA knees. However, additional systematic studies on the mechanisms of action of PEMF on joints and tissues therein, articular cartilage, tendons, and ligaments are required.
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Affiliation(s)
- Kenjiro Iwasa
- Department of Orthopaedic Surgery, Lawrence Ellison Center for Tissue Regeneration and Repair, School of Medicine, University of California , Davis, Davis, California
| | - A Hari Reddi
- Department of Orthopaedic Surgery, Lawrence Ellison Center for Tissue Regeneration and Repair, School of Medicine, University of California , Davis, Davis, California
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Magnetic Fields and Reactive Oxygen Species. Int J Mol Sci 2017; 18:ijms18102175. [PMID: 29057846 PMCID: PMC5666856 DOI: 10.3390/ijms18102175] [Citation(s) in RCA: 131] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Revised: 09/30/2017] [Accepted: 10/13/2017] [Indexed: 12/21/2022] Open
Abstract
Reactive oxygen species (ROS) ubiquitously exist in mammalian cells to participate in various cellular signaling pathways. The intracellular ROS levels are dependent on the dynamic balance between ROS generation and elimination. In this review, we summarize reported studies about the influences of magnetic fields (MFs) on ROS levels. Although in most cases, MFs increased ROS levels in human, mouse, rat cells, and tissues, there are also studies showing that ROS levels were decreased or not affected by MFs. Multiple factors could cause these discrepancies, including but not limited to MF type/intensity/frequency, exposure time and assay time-point, as well as different biological samples examined. It will be necessary to investigate the influences of different MFs on ROS in various biological samples systematically and mechanistically, which will be helpful for people to get a more complete understanding about MF-induced biological effects. In addition, reviewing the roles of MFs in ROS modulation may open up new scenarios of MF application, which could be further and more widely adopted into clinical applications, particularly in diseases that ROS have documented pathophysiological roles.
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Tschon M, Veronesi F, Contartese D, Sartori M, Martini L, Vincenzi F, Ravani A, Varani K, Fini M. Effects of pulsed electromagnetic fields and platelet rich plasma in preventing osteoclastogenesis in an in vitro model of osteolysis. J Cell Physiol 2017; 233:2645-2656. [PMID: 28786478 DOI: 10.1002/jcp.26143] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2017] [Accepted: 08/07/2017] [Indexed: 12/17/2022]
Abstract
Osteolysis is the main limiting cause for the survival of an orthopedic prosthesis and is accompanied by an enhancement in osteoclastogenesis and inflammation, due by wear debris formation. Unfortunately therapeutic treatments, besides revision surgery, are not available. The aim of the present study was to evaluate the effects of Pulsed Electro Magnetic Fields (PEMFs) and platelet rich plasma (PRP), alone or in combination, in an in vitro model of osteolysis. Rats peripheral blood mononuclear cells were cultured on Ultra High Molecular Weight Polyethylene particles and divided into four groups of treatments: (1) PEMF stimulation (12 hr/day, 2.5 mT, 75 Hz, 1.3 ms pulse duration); (2) 10% PRP; (3) combination of PEMFs, and PRP; (4) no treatment. Treatments were performed for 3 days and cell viability, osteoclast number, expression of genes related to osteoclastogenesis and inflammation and production of pro-inflammatory cytokines were assessed up to 14 days. PEMF stimulation exerted best results because it increased cell viability at early time points and counteracted osteoclastogenesis at 14 days. On the contrary, PRP increased osteoclastogenesis and reduced cell viability in comparison to PEMFs alone. The combination of PEMFs and PRP increased cell viability over time and reduced osteoclastogenesis in comparison to PRP alone. However, these positive results did not exceed the level achieved by PEMF alone. At longer time points PEMF could not counteract osteoclastogenesis increased by PRP. Regarding inflammation, all treatments maintained the production of pro-inflammatory cytokines at low level, although PRP increased the level of interleukin 1 beta.
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Affiliation(s)
- Matilde Tschon
- Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna, Italy
| | - Francesca Veronesi
- Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna, Italy
| | - Deyanira Contartese
- Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna, Italy
| | - Maria Sartori
- Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, Research Innovation and Technology Department (RIT), Rizzoli Orthopaedic Institute, Bologna, Italy
| | - Lucia Martini
- Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna, Italy
| | - Fabrizio Vincenzi
- Department of Medical Sciences, Laboratory of Cellular and Molecular Pharmacology, University of Ferrara, Ferrara, Italy
| | - Annalisa Ravani
- Department of Medical Sciences, Laboratory of Cellular and Molecular Pharmacology, University of Ferrara, Ferrara, Italy
| | - Katia Varani
- Department of Medical Sciences, Laboratory of Cellular and Molecular Pharmacology, University of Ferrara, Ferrara, Italy
| | - Milena Fini
- Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna, Italy
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Yang J, Zhang YS, Yue K, Khademhosseini A. Cell-laden hydrogels for osteochondral and cartilage tissue engineering. Acta Biomater 2017; 57:1-25. [PMID: 28088667 PMCID: PMC5545789 DOI: 10.1016/j.actbio.2017.01.036] [Citation(s) in RCA: 431] [Impact Index Per Article: 53.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2016] [Revised: 12/21/2016] [Accepted: 01/10/2017] [Indexed: 12/11/2022]
Abstract
Despite tremendous advances in the field of regenerative medicine, it still remains challenging to repair the osteochondral interface and full-thickness articular cartilage defects. This inefficiency largely originates from the lack of appropriate tissue-engineered artificial matrices that can replace the damaged regions and promote tissue regeneration. Hydrogels are emerging as a promising class of biomaterials for both soft and hard tissue regeneration. Many critical properties of hydrogels, such as mechanical stiffness, elasticity, water content, bioactivity, and degradation, can be rationally designed and conveniently tuned by proper selection of the material and chemistry. Particularly, advances in the development of cell-laden hydrogels have opened up new possibilities for cell therapy. In this article, we describe the problems encountered in this field and review recent progress in designing cell-hydrogel hybrid constructs for promoting the reestablishment of osteochondral/cartilage tissues. Our focus centers on the effects of hydrogel type, cell type, and growth factor delivery on achieving efficient chondrogenesis and osteogenesis. We give our perspective on developing next-generation matrices with improved physical and biological properties for osteochondral/cartilage tissue engineering. We also highlight recent advances in biomanufacturing technologies (e.g. molding, bioprinting, and assembly) for fabrication of hydrogel-based osteochondral and cartilage constructs with complex compositions and microarchitectures to mimic their native counterparts. STATEMENT OF SIGNIFICANCE Despite tremendous advances in the field of regenerative medicine, it still remains challenging to repair the osteochondral interface and full-thickness articular cartilage defects. This inefficiency largely originates from the lack of appropriate tissue-engineered biomaterials that replace the damaged regions and promote tissue regeneration. Cell-laden hydrogel systems have emerged as a promising tissue-engineering platform to address this issue. In this article, we describe the fundamental problems encountered in this field and review recent progress in designing cell-hydrogel constructs for promoting the reestablishment of osteochondral/cartilage tissues. Our focus centers on the effects of hydrogel composition, cell type, and growth factor delivery on achieving efficient chondrogenesis and osteogenesis. We give our perspective on developing next-generation hydrogel/inorganic particle/stem cell hybrid composites with improved physical and biological properties for osteochondral/cartilage tissue engineering. We also highlight recent advances in biomanufacturing and bioengineering technologies (e.g. 3D bioprinting) for fabrication of hydrogel-based osteochondral and cartilage constructs.
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Affiliation(s)
- Jingzhou Yang
- Biomaterials Innovation Research Center, Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston 02115, MA, USA; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Guangzhou Women and Children's Medical Center, Sun Yat-sen University, Guangzhou 510623, Guangdong, People's Republic of China
| | - Yu Shrike Zhang
- Biomaterials Innovation Research Center, Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston 02115, MA, USA; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
| | - Kan Yue
- Biomaterials Innovation Research Center, Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston 02115, MA, USA; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
| | - Ali Khademhosseini
- Biomaterials Innovation Research Center, Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston 02115, MA, USA; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Bioindustrial Technologies, College of Animal Bioscience and Technology, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea; Department of Physics, King Abdulaziz University, Jeddah 21569, Saudi Arabia.
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Vincenzi F, Ravani A, Pasquini S, Merighi S, Gessi S, Setti S, Cadossi R, Borea PA, Varani K. Pulsed Electromagnetic Field Exposure Reduces Hypoxia and Inflammation Damage in Neuron-Like and Microglial Cells. J Cell Physiol 2016; 232:1200-1208. [PMID: 27639248 DOI: 10.1002/jcp.25606] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2016] [Accepted: 09/14/2016] [Indexed: 12/11/2022]
Abstract
In the present study, the effect of low-frequency, low-energy pulsed electromagnetic fields (PEMFs) has been investigated by using different cell lines derived from neuron-like cells and microglial cells. In particular, the primary aim was to evaluate the effect of PEMF exposure in inflammation- and hypoxia-induced injury in two different neuronal cell models, the human neuroblastoma-derived SH-SY5Y cells and rat pheochromocytoma PC12 cells and in N9 microglial cells. In neuron-like cells, live/dead and apoptosis assays were performed in hypoxia conditions from 2 to 48 h. Interestingly, PEMF exposure counteracted hypoxia damage significantly reducing cell death and apoptosis. In the same cell lines, PEMFs inhibited the activation of the hypoxia-inducible factor 1α (HIF-1α), the master transcriptional regulator of cellular response to hypoxia. The effect of PEMF exposure on reactive oxygen species (ROS) production in both neuron-like and microglial cells was investigated considering their key role in ischemic injury. PEMFs significantly decreased hypoxia-induced ROS generation in PC12, SH-SY5Y, and N9 cells after 24 or 48 h of incubation. Moreover, PEMFs were able to reduce some of the most well-known pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-8 release in N9 microglial cells stimulated with different concentrations of LPS for 24 or 48 h of incubation time. These results show a protective effect of PEMFs on hypoxia damage in neuron-like cells and an anti-inflammatory effect in microglial cells suggesting that PEMFs could represent a potential therapeutic approach in cerebral ischemic conditions. J. Cell. Physiol. 232: 1200-1208, 2017. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Fabrizio Vincenzi
- Department of Medical Sciences, Institute of Pharmacology, University of Ferrara, Ferrara, Italy
| | - Annalisa Ravani
- Department of Medical Sciences, Institute of Pharmacology, University of Ferrara, Ferrara, Italy
| | - Silvia Pasquini
- Department of Medical Sciences, Institute of Pharmacology, University of Ferrara, Ferrara, Italy
| | - Stefania Merighi
- Department of Medical Sciences, Institute of Pharmacology, University of Ferrara, Ferrara, Italy
| | - Stefania Gessi
- Department of Medical Sciences, Institute of Pharmacology, University of Ferrara, Ferrara, Italy
| | | | | | - Pier Andrea Borea
- Department of Medical Sciences, Institute of Pharmacology, University of Ferrara, Ferrara, Italy
| | - Katia Varani
- Department of Medical Sciences, Institute of Pharmacology, University of Ferrara, Ferrara, Italy
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Beck A, Murphy DJ, Carey-Smith R, Wood DJ, Zheng MH. Treatment of Articular Cartilage Defects With Microfracture and Autologous Matrix-Induced Chondrogenesis Leads to Extensive Subchondral Bone Cyst Formation in a Sheep Model. Am J Sports Med 2016; 44:2629-2643. [PMID: 27436718 DOI: 10.1177/0363546516652619] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Microfracture and the autologous matrix-induced chondrogenesis (AMIC) technique are popular for the treatment of articular cartilage defects. However, breaching of the subchondral bone plate could compromise the subchondral bone structure. HYPOTHESIS Microfracture and AMIC will cause deleterious effects on the subchondral bone structure. STUDY DESIGN Controlled laboratory study. METHODS A total of 36 sheep received an 8-mm-diameter cartilage defect in the left medial femoral condyle. Control animals (n = 12) received no further treatment, and the rest received 5 microfracture holes either with a type I/III collagen scaffold implanted (n = 12; AMIC group) or without the collagen scaffold (n = 12; microfracture group). Macroscopic infill of defects, histology, and histomorphometry of the subchondral bone were performed at 13 and 26 weeks postoperatively, and micro-computed tomography (CT) was also performed at 26 weeks postoperatively. RESULTS Microfracture and AMIC resulted in subchondral bone cyst formation in 5 of 12 (42%) and 11 of 12 (92%) specimens at 13 and 26 weeks, respectively. Subchondral bone changes induced by microfracture and AMIC were characterized by an increased percentage of bone volume, increased trabecular thickness, and a decreased trabecular separation, and extended beyond the area below the defect. High numbers of osteoclasts were observed at the cyst periphery, and all cysts communicated with the microfracture holes. Cartilage repair tissue was of poor quality and quantity at both time points and rarely reached the tidemark at 13 weeks. CONCLUSION Microfracture technique caused bone cyst formation and induced severe pathology of the subchondral bone in a sheep model. CLINICAL RELEVANCE The potential of microfracture technique to induce subchondral bone pathology should be considered.
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Affiliation(s)
- Aswin Beck
- Centre for Orthopaedic Research (M508), School of Surgery, University of Western Australia, Crawley, Western Australia, Australia School of Veterinary and Life Sciences, Murdoch University, Murdoch, Western Australia, Australia
| | - David J Murphy
- School of Veterinary and Life Sciences, Murdoch University, Murdoch, Western Australia, Australia
| | - Richard Carey-Smith
- Perth Orthopaedic Institute, University of Western Australia, Nedlands, Western Australia, Australia
| | - David J Wood
- Perth Orthopaedic Institute, University of Western Australia, Nedlands, Western Australia, Australia
| | - Ming H Zheng
- Centre for Orthopaedic Research (M508), School of Surgery, University of Western Australia, Crawley, Western Australia, Australia
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Levy DM, Frank RM, Bach BR, Verma NN. Perioperative Pain and Swelling Control in Anterior Cruciate Ligament Reconstruction. OPER TECHN SPORT MED 2016. [DOI: 10.1053/j.otsm.2015.09.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Multi-layered collagen-based scaffolds for osteochondral defect repair in rabbits. Acta Biomater 2016; 32:149-160. [PMID: 26724503 DOI: 10.1016/j.actbio.2015.12.034] [Citation(s) in RCA: 146] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2015] [Revised: 12/15/2015] [Accepted: 12/23/2015] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Identification of a suitable treatment for osteochondral repair presents a major challenge due to existing limitations and an urgent clinical need remains for an off-the-shelf, low cost, one-step approach. A biomimetic approach, where the biomaterial itself encourages cellular infiltration from the underlying bone marrow and provides physical and chemical cues to direct these cells to regenerate the damaged tissue, provides a potential solution. To meet this need, a multi-layer collagen-based osteochondral defect repair scaffold has been developed in our group. AIM The objective of this study was to assess the in vivo response to this scaffold and determine its ability to direct regenerative responses in each layer in order to repair osteochondral tissue in a critical-sized defect in a rabbit knee. METHODS Multi-layer scaffolds, consisting of a bone layer composed of type I collagen (bovine source) and hydroxyapatite (HA), an intermediate layer composed of type I and type II collagen and HA; and a superficial layer composed of type I and type II collagen (porcine source) and hyaluronic acid (HyA), were implanted into critical size (3 × 5 mm) osteochondral defects created in the medial femoral condyle of the knee joint of New Zealand white rabbits and compared to an empty control group. Repair was assessed macroscopically, histologically and using micro-CT analysis at 12 weeks post implantation. RESULTS Analysis of repair tissue demonstrated an enhanced macroscopic appearance in the multi-layer scaffold group compared to the empty group. In addition, diffuse host cellular infiltration in the scaffold group resulted in tissue regeneration with a zonal organisation, with repair of the subchondral bone, formation of an overlying cartilaginous layer and evidence of an intermediate tidemark. CONCLUSION These results demonstrate the potential of this biomimetic multi-layered scaffold to support and guide the host reparative response in the treatment of osteochondral defects. STATEMENT OF SIGNIFICANCE Osteochondral defects, involving cartilage and the underlying subchondral bone, frequently occur in young active patients due to disease or injury. While some treatment options are available, success is limited and patients often eventually require joint replacement. To address this clinical need, a multi-layer collagen-based osteochondral defect repair scaffold designed to direct host-stem cell mediated tissue formation within each region, has been developed in our group. The present study investigates the in vivo response to this scaffold in a critical-sized defect in a rabbit knee. Results shows the scaffolds ability to guide the host reparative response leading to tissue regeneration with a zonal organisation, repair of the subchondral bone, formation of an overlying cartilaginous layer and evidence of an intermediate tidemark.
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Green CJ, Beck A, Wood D, Zheng MH. The biology and clinical evidence of microfracture in hip preservation surgery. J Hip Preserv Surg 2016; 3:108-23. [PMID: 27583147 PMCID: PMC5005050 DOI: 10.1093/jhps/hnw007] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2015] [Accepted: 01/11/2016] [Indexed: 01/01/2023] Open
Abstract
The use of microfracture in hip arthroscopy is increasing dramatically. However, recent reports raise concerns not only about the lack of evidence to support the clinical use of microfracture, but also about the potential harm caused by violation of the subchondral bone plate. The biology and pathology of the microfracture technique were described based on observations in translational models and the clinical evidence for hip microfracture was reviewed systematically. The clinical outcomes in patients undergoing microfracture were the same as those not undergoing microfracture. However, the overall clinical evidence quality is poor in hips. This review identified only one study with Level III evidence, while most studies were Level IV. There were no randomized trials available for review. Repair tissue is primarily of fibrocartilaginous nature. Reconstitution of the subchondral bone is often incomplete and associated with poor quality repair tissue and faster degeneration. Subchondral bone cyst formation is associated with microfracture, likely secondary to subchondral bone plate disruption and a combination of pressurized synovial fluid and inflammatory mediators moving from the joint into the bone. There is a lack of clinical efficacy evidence for patients undergoing microfracture. There is evidence of bone cyst formation following microfracture in animal studies, which may accelerate joint degeneration. Bone cyst formation following microfracture has not been studied adequately in humans.
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Affiliation(s)
- Chadwick John Green
- Department of Orthopaedic Surgery, Royal Perth Hospital, Perth 6000, Australia and
| | - Aswin Beck
- Centre for Orthopaedic Research, School of Surgery, University of Western Australia, Nedlands 6009, Australia
| | - David Wood
- Centre for Orthopaedic Research, School of Surgery, University of Western Australia, Nedlands 6009, Australia
| | - Ming H Zheng
- Centre for Orthopaedic Research, School of Surgery, University of Western Australia, Nedlands 6009, Australia
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Servodio Iammarrone C, Cadossi M, Sambri A, Grosso E, Corrado B, Servodio Iammarrone F. Is there a role of pulsed electromagnetic fields in management of patellofemoral pain syndrome? Randomized controlled study at one year follow-up. Bioelectromagnetics 2016; 37:81-8. [PMID: 26756278 DOI: 10.1002/bem.21953] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2015] [Accepted: 12/12/2015] [Indexed: 12/30/2022]
Abstract
Patellofemoral pain syndrome (PFPS) is a common cause of recurrent or chronic knee pain in young adults, generally located in the retropatellar region. Etiology is controversial and includes several factors, such as anatomical defects, muscular imbalance, or joint overuse. Good results have been reported with exercise therapy, including home exercise program (HEP). Joint inflammation with increase of pro-inflammatory cytokines levels in the synovial fluid might be seen especially when chondromalacia becomes evident. Biophysical stimulation with pulsed electromagnetic fields (PEMFs) has shown anti-inflammatory effects and anabolic chondrocyte activity. The purpose of this randomized controlled study was to evaluate if the combination of HEP with PEMFs was more effective than HEP alone in PFPS treatment. Thirty-one PFPS patients were enrolled in this study. All patients were instructed to train with HEP. Patients in the PEMFs group associated HEP with PEMFs. Function and pain were assessed with Victorian Institute of Sport Assessment score (VISA), Visual Analog Scale (VAS), and Feller's Patella Score at baseline at 2, 6, and 12 months of follow-up. Drug assumption was also recorded. Increase in VISA score was significantly higher in PEMFs group compared to controls at 6 and 12 months, as well as the increase in the Feller's Patella Score at 12 months. VAS score became significantly lower in the PEMFs group with respect to control group since 6 month follow-up. Pain reduction obtained with PEMFs enhanced practicing therapeutic exercises leading to a better recovery process; this is extremely important in addressing the expectations of young patients, who wish to return to sporting activities.
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Affiliation(s)
| | | | | | - Eugenio Grosso
- Università degli Studi di Napoli "FEDERICO II" cattedra di Medicina Fisica e Riabilitativa, Napoli, Italy
| | - Bruno Corrado
- Università degli Studi di Napoli "FEDERICO II" cattedra di Medicina Fisica e Riabilitativa, Napoli, Italy
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Effects of PEMF on patients with osteoarthritis: Results of a prospective, placebo-controlled, double-blind study. Bioelectromagnetics 2015; 36:576-85. [DOI: 10.1002/bem.21942] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2015] [Accepted: 10/10/2015] [Indexed: 12/12/2022]
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de Girolamo L, Viganò M, Galliera E, Stanco D, Setti S, Marazzi MG, Thiebat G, Corsi Romanelli MM, Sansone V. In vitro functional response of human tendon cells to different dosages of low-frequency pulsed electromagnetic field. Knee Surg Sports Traumatol Arthrosc 2015; 23:3443-53. [PMID: 24957914 DOI: 10.1007/s00167-014-3143-x] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2013] [Accepted: 06/12/2014] [Indexed: 11/29/2022]
Abstract
PURPOSE Chronic tendinopathy is a degenerative process causing pain and disability. Current treatments include biophysical therapies, such as pulsed electromagnetic fields (PEMF). The aim of this study was to compare, for the first time, the functional in vitro response of human tendon cells to different dosages of PEMF, varying in field intensity and duration and number of exposures. METHODS Tendon cells, isolated from human semitendinosus and gracilis tendons (hTCs; n = 6), were exposed to different PEMF treatments (1.5 or 3 mT for 8 or 12 h, single or repeated treatments). Scleraxis (SCX), COL1A1, COL3A1 and vascular endothelial growth factor-A (VEGF-A) expression and cytokine production were assessed. RESULTS None of the different dosages provoked apoptotic events. Proliferation of hTCs was enhanced by all treatments, whereas only 3 mT-PEMF treatment increased cell viability. However, the single 1.5 mT-PEMF treatment elicited the highest up-regulation of SCX, VEGF-A and COL1A1 expression, and it significantly reduced COL3A1 expression with respect to untreated cells. The treated hTCs showed a significantly higher release of IL-1β, IL-6, IL-10 and TGF-β. Interestingly, the repeated 1.5 mT-PEMF significantly further increased IL-10 production. CONCLUSIONS 1.5 mT-PEMF treatment was able to give the best results in in vitro healthy human tendon cell culture. Although the clinical relevance is not direct, this investigation should be considered an attempt to clarify the effect of different PEMF protocols on tendon cells, in particular focusing on the potential applicability of this cell source for regenerative medicine purpose, both in surgical and in conservative treatment for tendon disorders.
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Affiliation(s)
- L de Girolamo
- Orthopaedic Biotechnology Laboratory, IRCCS Istituto Ortopedico Galeazzi, Via R. Galeazzi, 4, 20161, Milan, Italy.
| | - M Viganò
- Orthopaedic Biotechnology Laboratory, IRCCS Istituto Ortopedico Galeazzi, Via R. Galeazzi, 4, 20161, Milan, Italy
| | - E Galliera
- Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, Università degli Studi di Milano, Milan, Italy.,IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
| | - D Stanco
- Orthopaedic Biotechnology Laboratory, IRCCS Istituto Ortopedico Galeazzi, Via R. Galeazzi, 4, 20161, Milan, Italy
| | - S Setti
- IGEA SpA, Clinical Biophysics, Carpi, Italy
| | - M G Marazzi
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy
| | - G Thiebat
- Sport Traumatology Unit, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
| | - M M Corsi Romanelli
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy.,IRCCS Policlinico San Donato, San Donato Milanese, Italy
| | - V Sansone
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy.,Orthopaedic Department, Istituto Ortopedico Galeazzi, Milan, Italy
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Veronesi F, Fini M, Giavaresi G, Ongaro A, De Mattei M, Pellati A, Setti S, Tschon M. Experimentally induced cartilage degeneration treated by pulsed electromagnetic field stimulation; an in vitro study on bovine cartilage. BMC Musculoskelet Disord 2015; 16:308. [PMID: 26480822 PMCID: PMC4616002 DOI: 10.1186/s12891-015-0760-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2015] [Accepted: 10/07/2015] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Osteoarthritis (OA) is the final result of progressive alterations to articular cartilage structure, composition and cellularity, followed by an increase in the concentration of pro-inflammatory cytokines in joint synovial fluid. Even though the effect of pulsed electromagnetic field (PEMF) stimulation in counteracting OA progression and inflammation is of increasing interest, because of its anabolic and anti-inflammatory properties, the present study aimed to improve the knowledge on cartilage extracellular matrix (ECM) and chondrocyte changes related to the exposure of PEMF, from a histological and histomorphometric point of view. METHODS An in vitro OA model was realized, culturing bovine cartilage explants with a high dose of interleukin 1β (IL1β, 50 ng/ml) at different experimental times (24 h, and 7 and 21 days). The effects of PEMFs (75 Hz, 1.5 mT) were evaluated in cartilage explants treated with IL1β or not (control), in terms of cartilage structure, cellularity and proteoglycans, glycosaminoglycans, collagen II and transforming growth factor β1 synthesis by using histology, histomorphometry and immunohistochemistry. RESULTS Making a comparison with control cartilage, IL1β-treated explants showed a decrease in cartilage matrix, structure and cellularity parameters. PEMFs were able to counteract the progression of OA acting on both cartilage cellularity and ECM in cartilage previously treated with IL1β. Normal distribution (Kolmogroc-Smirnov test) and homoscedasticity (Levene test) of data were verified, then, the non-parametric Kruskal Wallis test followed by Mann-Whiteny U test for pairwise comparisons were performed. The p-value was adjusted according to the Dunn-Sidak correction. CONCLUSIONS These results, obtained by culturing and treating cartilage explants from two different joints, confirmed that PEMF stimulation can be used as adjuvant therapy to preserve cartilage from detrimental effects of high inflammatory cytokine levels during OA.
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Affiliation(s)
- Francesca Veronesi
- Department Rizzoli RIT, Rizzoli Orthopedic Institute, Laboratory of Biocompatibility, Innovative Technologies and Advanced Therapies, Bologna, 40136, Italy.
| | - Milena Fini
- Department Rizzoli RIT, Rizzoli Orthopedic Institute, Laboratory of Biocompatibility, Innovative Technologies and Advanced Therapies, Bologna, 40136, Italy. .,Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna, 40136, Italy.
| | - Gianluca Giavaresi
- Department Rizzoli RIT, Rizzoli Orthopedic Institute, Laboratory of Biocompatibility, Innovative Technologies and Advanced Therapies, Bologna, 40136, Italy. .,Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna, 40136, Italy.
| | - Alessia Ongaro
- Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, 44121, Italy.
| | - Monica De Mattei
- Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, 44121, Italy.
| | - Agnese Pellati
- Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, 44121, Italy.
| | - Stefania Setti
- IGEA - Clinical Biophysic, Carpi (Modena), 41012, Italy.
| | - Matilde Tschon
- Department Rizzoli RIT, Rizzoli Orthopedic Institute, Laboratory of Biocompatibility, Innovative Technologies and Advanced Therapies, Bologna, 40136, Italy. .,Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna, 40136, Italy.
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Veronesi F, Cadossi M, Giavaresi G, Martini L, Setti S, Buda R, Giannini S, Fini M. Pulsed electromagnetic fields combined with a collagenous scaffold and bone marrow concentrate enhance osteochondral regeneration: an in vivo study. BMC Musculoskelet Disord 2015; 16:233. [PMID: 26328626 PMCID: PMC4557597 DOI: 10.1186/s12891-015-0683-2] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2015] [Accepted: 08/13/2015] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND The study aimed to evaluate the combined effect of Pulsed Electromagnetic Field (PEMF) biophysical stimulation and bone marrow concentrate (BMC) in osteochondral defect healing in comparison to the treatment with scaffold alone. METHODS An osteochondral lesion of both knees was performed in ten rabbits. One was treated with a collagen scaffold alone and the other with scaffold seeded with BMC. Half of the animals were stimulated by PEMFs (75 Hz, 1.5 mT, 4 h/day) and at 40 d, macroscopic, histological and histomorphometric analyses were performed to evaluate osteochondral defect regeneration. RESULTS Regarding cartilage, the addition of BMC to the scaffold improved cell parameters and the PEMF stimulation improved both cell and matrix parameters compared with scaffold alone. The combination of BMC and PEMFs further improved osteochondral regeneration: there was an improvement in macroscopic, cartilage cellularity and matrix parameters and a reduction in the percentage of cartilage under the tidemark. Epiphyseal bone healing improved in all the osteochondral defects regardless of treatment, although PEMFs alone did not significantly improve the reconstruction of subchondral bone in comparison to treatment with scaffold alone. CONCLUSIONS Results show that BMC and PEMFs might have a separate effect on osteochondral regeneration, but it seems that they have a greater effect when used together. Biophysical stimulation is a non-invasive therapy, free from side effects and should be started soon after BMC transplantation to increase the quality of the regenerated tissue. However, because this is the first explorative study on the combination of a biological and a biophysical treatment for osteochondral regeneration, future preclinical and clinical research should be focused on this topic to explore mechanisms of action and the correct clinical translation.
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Affiliation(s)
- Francesca Veronesi
- Department Rizzoli RIT, Laboratory of Biocompatibility Innovative Technologies and Advanced Therapies, Via Di Barbiano 1/10, 40136, Bologna, Italy.
| | - Matteo Cadossi
- I Orthopaedics and Trauma Clinic, Rizzoli Orthopaedic Institute, Via Di Barbiano 1/10, 40136, Bologna, Italy. .,University of Bologna, Bologna, Italy.
| | - Gianluca Giavaresi
- Department Rizzoli RIT, Laboratory of Biocompatibility Innovative Technologies and Advanced Therapies, Via Di Barbiano 1/10, 40136, Bologna, Italy. .,Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute, Via Di Barbiano 1/10, 40136, Bologna, Italy.
| | - Lucia Martini
- Department Rizzoli RIT, Laboratory of Biocompatibility Innovative Technologies and Advanced Therapies, Via Di Barbiano 1/10, 40136, Bologna, Italy. .,Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute, Via Di Barbiano 1/10, 40136, Bologna, Italy.
| | - Stefania Setti
- IGEA S.p.A., via Parmenide 10/A, 41012, Carpi, Modena, Italy.
| | - Roberto Buda
- I Orthopaedics and Trauma Clinic, Rizzoli Orthopaedic Institute, Via Di Barbiano 1/10, 40136, Bologna, Italy. .,University of Bologna, Bologna, Italy.
| | | | - Milena Fini
- Department Rizzoli RIT, Laboratory of Biocompatibility Innovative Technologies and Advanced Therapies, Via Di Barbiano 1/10, 40136, Bologna, Italy. .,Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute, Via Di Barbiano 1/10, 40136, Bologna, Italy.
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Cadossi M, Buda RE, Ramponi L, Sambri A, Natali S, Giannini S. Bone marrow-derived cells and biophysical stimulation for talar osteochondral lesions: a randomized controlled study. Foot Ankle Int 2014; 35:981-7. [PMID: 24917648 DOI: 10.1177/1071100714539660] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Osteochondral lesions of the talus (OLT) frequently occur after ankle sprains in young patients participating in sports activities. These injuries may lead to chronic pain, joint swelling, and finally osteoarthritis, therefore, surgical repair is frequently needed. A collagen scaffold seeded with bone marrow-derived cells (BMDCs) harvested from patient's iliac crest and implanted into the OLT through a single arthroscopic procedure has been recently proposed as an effective treatment option. Nevertheless, BMDCs, embedded in an inflammatory environment, tend to differentiate toward a fibroblast phenotype with a consequential loss of mechanical characteristics. Biophysical stimulation with pulsed electromagnetic fields (PEMFs) has been shown to promote anabolic chondrocyte activity, stimulate proteoglycan synthesis, and reduce the release of the most relevant pro-inflammatory cytokines. The aim of this randomized controlled trial was to evaluate the effects of PEMFs on clinical outcome in patients who underwent BMDCs transplantation for OLT. METHODS Thirty patients affected by grade III and IV Outerbridge OLT underwent BMDCs transplantation. After surgery, patients were randomly assigned to either experimental group (PEMFs 4 hours per day for 60 days starting within 3 days after operation) or control group. Clinical outcome was evaluated with (American Orthopaedic Foot and Ankle Society) AOFAS score, Visual Analog Scale (VAS), and Short Form-36 (SF-36). RESULTS Significantly higher AOFAS score was recorded in the experimental group both at 6 or 12 months follow-up. At 60 days and 6 and 12 months follow-up, significant lower pain was observed in the experimental group. No significant difference was found in SF-36 between groups. CONCLUSION A superior clinical outcome was found in the experimental group with more than 10 points higher AOFAS score at final follow-up. Biophysical stimulation started soon after surgery aided patient recovery leading to pain control and a better clinical outcome with these improvements lasting more than 1 year after surgery. LEVEL OF EVIDENCE Level II, prospective comparative study.
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Affiliation(s)
- Matteo Cadossi
- Rizzoli Orthopaedic Institute, Bologna, Italy University of Bologna, Bologna, Italy
| | | | | | | | | | - Sandro Giannini
- Rizzoli Orthopaedic Institute, Bologna, Italy University of Bologna, Bologna, Italy
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Low-intensity pulsed ultrasound (LIPUS) and pulsed electromagnetic field (PEMF) treatments affect degeneration of cultured articular cartilage explants. INTERNATIONAL ORTHOPAEDICS 2014; 39:549-57. [PMID: 25267432 DOI: 10.1007/s00264-014-2542-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/11/2014] [Accepted: 09/16/2014] [Indexed: 12/15/2022]
Abstract
PURPOSE Articular cartilage has some capacity for self-repair. Clinically used low-intensity pulsed ultrasound (LIPUS) and pulsed electromagnetic field (PEMF) treatments were compared in their potency to prevent degeneration using an explant model of porcine cartilage. METHODS Explants of porcine cartilage and human osteoarthritic cartilage were cultured for four weeks and subjected to daily LIPUS or PEMF treatments. At one, two, three and four weeks follow-up explants were prepared for histological assessment or gene expression (porcine only). RESULTS Non-treated porcine explants showed signs of atrophy of the superficial zone starting at one week. Treated explants did not. In LIPUS-treated explants cell clusters were observed. In PEMF-treated explants more hypertrophic-like changes were observed at later follow up. Newly synthesized tissue was present in treated explants. Gene expression profiles did indicate differences between the two methods. Both methods reduced expression of the aggrecan and collagen type II gene compared to the control. LIPUS treatment of human cartilage samples resulted in a reduction of degeneration according to Mankin scoring. PEMF treatment did not. CONCLUSIONS LIPUS or PEMF prevented degenerative changes in pig knee cartilage explants. LIPUS reduced degeneration in human cartilage samples. LIPUS treatment seems to have more potency in the treatment of osteoarthritis than PEMF treatment.
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Hu J, Zhang T, Xu D, Qu J, Qin L, Zhou J, Lu H. Combined magnetic fields accelerate bone‐tendon junction injury healing through osteogenesis. Scand J Med Sci Sports 2014; 25:398-405. [PMID: 24845774 DOI: 10.1111/sms.12251] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/13/2014] [Indexed: 12/29/2022]
Affiliation(s)
- J. Hu
- Department of Sports Medicine, Research Center of Sports Medicine Xiangya Hospital Central South University Changsha Hunan China
- Department of Spine Surgery Xiangya Hospital Central South University Changsha Hunan China
| | - T. Zhang
- Department of Sports Medicine, Research Center of Sports Medicine Xiangya Hospital Central South University Changsha Hunan China
- Department of Spine Surgery Xiangya Hospital Central South University Changsha Hunan China
| | - D. Xu
- Department of Sports Medicine, Research Center of Sports Medicine Xiangya Hospital Central South University Changsha Hunan China
| | - J. Qu
- Department of Sports Medicine, Research Center of Sports Medicine Xiangya Hospital Central South University Changsha Hunan China
- Department of Spine Surgery Xiangya Hospital Central South University Changsha Hunan China
| | - L. Qin
- Department of Orthopaedics and Traumatology The Chinese University of Hong Kong Hong Kong SAR China
| | - J. Zhou
- Department of Sports Medicine, Research Center of Sports Medicine Xiangya Hospital Central South University Changsha Hunan China
| | - H. Lu
- Department of Sports Medicine, Research Center of Sports Medicine Xiangya Hospital Central South University Changsha Hunan China
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Farr J, Jaggers R, Lewis H, Plackis A, Sim SB, Sherman SL. Evidence-based approach of treatment options for postoperative knee pain. PHYSICIAN SPORTSMED 2014; 42:58-70. [PMID: 24875973 DOI: 10.3810/psm.2014.05.2058] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Optimal pain management is critical after knee surgery to avoid adverse events and to improve surgical outcomes. Pain may affect surgical outcomes by contributing to limitations in range of motion, strength, and functional recovery. The causes of postoperative pain are multifactorial; therefore, an appropriate pain management strategy must take into account preoperative, intraoperative, and postoperative factors to create a comprehensive and individualized plan for the patient. Preoperative assessment includes management of patient expectations, recognition of conditions and early counseling for high-risk patients (ie, opioid dependence, psychiatric comorbidities), and use of preemptive analgesia techniques (ie, preoperative IV medications, peripheral nerve blocks, incisional field blocks). Intraoperative strategies include meticulous surgical technique, limiting the use of tourniquets (ie, duration and pressure), and using preventive analgesia methods (ie, postoperative field block, continuous nerve catheters, intra-articular injection). Postoperative analgesia may be facilitated by cryotherapy, early mobilization, bracing, and rehabilitation. Certain modalities (ie, continuous passive motion devices, transcutaneous electrical nerve stimulation units, iontophoresis) may be important adjuncts in the perioperative period as well. There may be an evolving role for alternative medicine strategies. Early recognition and treatment of exaggerated postoperative pain responses may mitigate the effects of complex regional pain syndrome or the development of chronic pain.
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Affiliation(s)
- Jack Farr
- Cartilage Restoration Center of Indiana, Greenwood, IN
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Veronesi F, Torricelli P, Giavaresi G, Sartori M, Cavani F, Setti S, Cadossi M, Ongaro A, Fini M. In vivo effect of two different pulsed electromagnetic field frequencies on osteoarthritis. J Orthop Res 2014; 32:677-85. [PMID: 24501089 DOI: 10.1002/jor.22584] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2013] [Accepted: 01/06/2014] [Indexed: 02/04/2023]
Abstract
Osteoarthritis (OA) is a joint pathology characterized by fibrillation, reduced cartilage thickness and subchondral bone sclerosis. There is evidence that pulsed electromagnetic fields (PEMFs) counteract OA progression, but the effect of two different PEMF frequencies has not yet been shown. The aim of this study was to test the effectiveness of PEMFs at two different frequencies (37 and 75 Hz) in a late OA stage in 21-month-old Guinea pigs. After 3 months of 6 h/day PEMF stimulation, histological and histomorphometric analyses of the knees were performed. At both frequencies, PEMFs significantly reduced histological cartilage score, fibrillation index (FI), subchondral bone thickness (SBT) and trabecular number (Tb.N) and increased trabecular thickness (Tb.Th) and separation (Tb.Sp) in comparison to the not treated SHAM group. However, PEMFs at 75 Hz produced significantly more beneficial effects on the histological score and FI than 37 Hz PEMFs. At 75 Hz, PEMFs counteracted cartilage thinning as demonstrated by a significantly higher cartilage thickness values than either those of the SHAM or 37 Hz PEMF-treated groups. Although in severe OA both PEMF frequencies were able to limit its progression, 75 Hz PEMF stimulation achieved the better results.
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Affiliation(s)
- F Veronesi
- Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute-IOR, via Di Barbiano 1/10, 40136, Bologna, Italy
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Pallante-Kichura AL, Cory E, Bugbee WD, Sah RL. Bone cysts after osteochondral allograft repair of cartilage defects in goats suggest abnormal interaction between subchondral bone and overlying synovial joint tissues. Bone 2013; 57:259-68. [PMID: 23958821 PMCID: PMC3817208 DOI: 10.1016/j.bone.2013.08.011] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2013] [Revised: 07/11/2013] [Accepted: 08/12/2013] [Indexed: 02/04/2023]
Abstract
The efficacy of osteochondral allografts (OCAs) may be affected by osseous support of the articular cartilage, and thus affected by bone healing and remodeling in the OCA and surrounding host. Bone cysts, and their communication pathways, may be present in various locations after OCA insertion and reflect distinct pathogenic mechanisms. Previously, we analyzed the effect of OCA storage (FRESH, 4°C/14d, 4°C/28d, FROZEN) on cartilage quality in fifteen adult goats after 12months in vivo. The objectives of this study were to further analyze OCAs and contralateral non-operated (Non-Op) CONTROLS from the medial femoral condyle to (1) determine the effect of OCA storage on local subchondral bone (ScB) and trabecular bone (TB) structure, (2) characterize the location and structure of bone cysts and channels, and (3) assess the relationship between cartilage and bone properties. (1) Overall bone structure after OCAs was altered compared to Non-Op, with OCA samples displaying bone cysts, ScB channels, and ScB roughening. ScB BV/TV in FROZEN OCAs was lower than Non-Op and other OCAs. TB BV/TV in FRESH, 4°C/14d, and 4°C/28d OCAs did not vary compared to Non-Op, but BS/TV was lower. (2) OCAs contained "basal" cysts, localized to deeper regions, some "subchondral" cysts, localized near the bone-cartilage interface, and some ScB channels. TB surrounding basal cysts exhibited higher BV/TV than Non-Op. (3) Basal cysts occurred (a) in isolation, (b) with subchondral cysts and ScB channels, (c) with ScB channels, or (d) with subchondral cysts, ScB channels, and ScB erosion. Deterioration of cartilage gross morphology was strongly associated with abnormal μCT bone structure. Evidence of cartilage-bone communication following OCA repair may favor fluid intrusion as a mechanism for subchondral cyst formation, while bone resorption at the graft-host interface without affecting overall bone and cartilage structure may favor bony contusion mechanism for basal cyst formation. These findings suggest that cysts occurring after OCAs may result from aberrant mechanobiology due to (1) altered compartmentalization that normally separates overlying cartilage and subchondral bone, either from distinct ScB channels or more general ScB plate deterioration, and (2) bone resorption at the basal graft-host interface.
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Affiliation(s)
- Andrea L. Pallante-Kichura
- Department of Bioengineering, University of California-San Diego, 9500 Gilman Drive, MC 0412, La Jolla, CA 92093-0412, USA
| | - Esther Cory
- Department of Bioengineering, University of California-San Diego, 9500 Gilman Drive, MC 0412, La Jolla, CA 92093-0412, USA
| | - William D. Bugbee
- Department of Orthopaedic Surgery, University of California-San Diego, 200 West Arbor Drive, MC 8894, San Diego, CA 92103-8894, USA
- Division of Orthopaedic Surgery, Scripps Clinic, 10666 N. Torrey Pines Road, La Jolla, CA 92037, USA
| | - Robert L. Sah
- Department of Bioengineering, University of California-San Diego, 9500 Gilman Drive, MC 0412, La Jolla, CA 92093-0412, USA
- Department of Orthopaedic Surgery, University of California-San Diego, 200 West Arbor Drive, MC 8894, San Diego, CA 92103-8894, USA
- Institute of Engineering in Medicine, Center for Musculoskeletal Research, University of California-San Diego, 9500 Gilman Drive MC 0435, La Jolla, CA 92093-0435, USA
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Fini M, Pagani S, Giavaresi G, De Mattei M, Ongaro A, Varani K, Vincenzi F, Massari L, Cadossi M. Functional Tissue Engineering in Articular Cartilage Repair: Is There a Role for Electromagnetic Biophysical Stimulation? TISSUE ENGINEERING PART B-REVIEWS 2013; 19:353-67. [DOI: 10.1089/ten.teb.2012.0501] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Affiliation(s)
- Milena Fini
- Laboratory of Preclinical and Surgical Studies, Technological Innovations, and Advanced Therapies, Rizzoli Orthopaedic Institute, Bologna, Italy
- Laboratory of Biocompatibility, Technological Innovations, and Advanced Therapies, Rizzoli Orthopaedic Institute, Bologna, Italy
| | - Stefania Pagani
- Laboratory of Preclinical and Surgical Studies, Technological Innovations, and Advanced Therapies, Rizzoli Orthopaedic Institute, Bologna, Italy
- Laboratory of Biocompatibility, Technological Innovations, and Advanced Therapies, Rizzoli Orthopaedic Institute, Bologna, Italy
| | - Gianluca Giavaresi
- Laboratory of Preclinical and Surgical Studies, Technological Innovations, and Advanced Therapies, Rizzoli Orthopaedic Institute, Bologna, Italy
- Laboratory of Biocompatibility, Technological Innovations, and Advanced Therapies, Rizzoli Orthopaedic Institute, Bologna, Italy
| | - Monica De Mattei
- Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy
| | - Alessia Ongaro
- Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy
| | - Katia Varani
- Department of Clinical and Experimental Medicine, University of Ferrara, Ferrara, Italy
| | - Fabrizio Vincenzi
- Department of Clinical and Experimental Medicine, University of Ferrara, Ferrara, Italy
| | - Leo Massari
- Department of Biomedical Sciences and Advanced Therapies, St. Anna Hospital, Ferrara, Italy
| | - Matteo Cadossi
- II Orthopaedics and Trauma Clinic, Rizzoli Orthopaedic Institute, Bologna, Italy
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Abstract
This article reviews the basics of articular cartilage biology, which provide a necessary foundation for understanding the evolving field of articular cartilage injury and repair. The currently popular treatment options for osteochondral injury (microfracture, osteochondral autograft transfer system, osteochondral allograft, autologous chondrocyte implantation, and the use of scaffolds with autologous chondrocyte implantation) document the significant advances made in this area in the past 2 decades. Integration of newly available information and technology derived from advances in molecular biology and tissue engineering holds even greater promise for continued advances in optimal management of this challenging problem.
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Affiliation(s)
- Rachel Triche
- Santa Monica Orthopaedic and Sports Medicine Group, 2020 Santa Monica Boulevard, Suite 400, Santa Monica, CA 90404, USA.
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47
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van Eekeren ICM, Reilingh ML, van Dijk CN. Rehabilitation and return-to-sports activity after debridement and bone marrow stimulation of osteochondral talar defects. Sports Med 2013; 42:857-70. [PMID: 22963224 DOI: 10.1007/bf03262299] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
An osteochondral defect (OD) is a lesion involving the articular cartilage and the underlying subchondral bone. ODs of the talus can severely impact on the quality of life of patients, who are usually young and athletic. The primary treatment for ODs that are too small for fixation, consists of arthroscopic debridement and bone marrow stimulation. This article delineates levels of activity, determines times for return to activity and reviews the factors that affect rehabilitation after arthroscopic debridement and bone marrow stimulation of a talar OD. Articles for review were obtained from a search of the MEDLINE database up to January 2012 using the search headings 'osteochondral defects', 'bone marrow stimulation', 'sports/activity', 'rehabilitation', various other related factors and 'talus'. English-, Dutch- and German-language studies were evaluated.The review revealed that there is no consensus in the existing literature about rehabilitation times or return-to-sports activity times, after treatment with bone marrow stimulation of ODs in the talus. Furthermore, scant research has been conducted on these issues. The literature also showed that potential factors that aid rehabilitation could include youth, lower body mass index, smaller OD size, mobilization and treatment with growth factors, platelet-rich plasma, biphosphonates, hyaluronic acid and pulse electromagnetic fields. However, most studies have been conducted in vitro or on animals. We propose a scheme, whereby return-to-sports activity is divided into four phases of increasing intensity: walking, jogging, return to non-contact sports (running without swerving) and return to contact sports (running with swerving and collision). We also recommend that research, conducted on actual sportsmen, of recovery times after treatment of talar ODs is warranted.
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Affiliation(s)
- Inge C M van Eekeren
- Orthopedic Research Centre Amsterdam, Department of Orthopedic Surgery, Academic Medical Centre, Amsterdam, The Netherlands.
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Orth P, Madry H. A low morbidity surgical approach to the sheep femoral trochlea. BMC Musculoskelet Disord 2013; 14:5. [PMID: 23286467 PMCID: PMC3539878 DOI: 10.1186/1471-2474-14-5] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2012] [Accepted: 12/31/2012] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The ovine stifle joint is an important location for investigations on the repair of articular cartilage defects in preclinical large animals. The classical medial parapatellar approach to the femoral trochlea is hazardous because of the high risk of postoperative patellar luxation. Here, we describe a low morbidity surgical exposure of the ovine trochlea without the necessity for intraoperative patellar luxation. METHODS Bilateral surgical exposure of the femoral trochlea of the sheep stifle joint was performed using the classical medial parapatellar approach with intraoperative lateral patellar luxation and transection of the medial patellar retinaculum in 28 ovine stifle joints. A low morbidity approach was performed bilaterally in 116 joints through a mini-arthrotomy without the need to transect the medial patellar retinaculum or the oblique medial vastus muscle nor surgical patellar luxation. Postoperatively, all 72 animals were monitored to exclude patellar luxations and deep wound infections. RESULTS The novel approach could be performed easily in all joints and safely exposed the distal two-thirds of the medial and lateral trochlear facet. No postoperative patellar luxations were observed compared to a postoperative patellar luxation rate of 25% experienced with the classical medial parapatellar approach and a re-luxation rate of 80% following revision surgery. No signs of lameness, wound infections, or empyema were observed for both approaches. CONCLUSIONS The mini-arthrotomy presented here yields good exposure of the distal ovine femoral trochlea with a lower postoperative morbidity than the classical medial parapatellar approach. It is therefore suitable to create articular cartilage defects on the femoral trochlea without the risk of postoperative patellar luxation.
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Affiliation(s)
- Patrick Orth
- Center of Experimental Orthopaedics and Osteoarthritis Research, Saarland University, Saar, Germany
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49
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Pape D, Madry H. The preclinical sheep model of high tibial osteotomy relating basic science to the clinics: standards, techniques and pitfalls. Knee Surg Sports Traumatol Arthrosc 2013; 21:228-36. [PMID: 22820740 DOI: 10.1007/s00167-012-2135-y] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2012] [Accepted: 07/02/2012] [Indexed: 11/27/2022]
Abstract
PURPOSE To develop a preclinical large animal model of high tibial osteotomy to study the effect of axial alignment on the lower extremity on specific issues of the knee joint, such as in articular cartilage repair, development of osteoarthritis and meniscal lesions. Preoperative planning, surgical procedure and postoperative care known from humans were adapted to develop a HTO model in the adult sheep. METHODS Thirty-five healthy, skeletally mature, female Merino sheep between 2 and 4 years of age underwent a HTO of their right tibia in a medial open-wedge technique inducing a normal (group 1) and an excessive valgus alignment (group 2) and a closed-wedge technique (group 3) inducing a varus alignment with the aim of elucidating the effect of limb alignment on cartilage repair in vivo. Animals were followed up for 6 months. RESULTS Solid bone healing and maintenance of correction are most likely if the following surgical principles are respected: (1) medial and longitudinal approach to the proximal tibia; (2) biplanar osteotomy to increase initial rotatory stability regardless of the direction of correction; (3) small, narrow but long implant with locking screws; (4) posterior plate placement to avoid slope changes; (5) use of bicortical screws to account for the brittle bone of the tibial head and to avoid tibial head displacement. CONCLUSION Although successful high tibial osteotomy in sheep is complex, the sheep may--because of its similarities with humans--serve as an elegant model to induce axial malalignment in a clinically relevant environment, and osteotomy healing under challenging mechanical conditions.
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Affiliation(s)
- Dietrich Pape
- Department of Orthopaedic Surgery, Centre Hospitalier de Luxembourg, 1460, Luxembourg, Luxembourg.
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Ongaro A, Pellati A, Setti S, Masieri FF, Aquila G, Fini M, Caruso A, De Mattei M. Electromagnetic fields counteract IL-1β activity during chondrogenesis of bovine mesenchymal stem cells. J Tissue Eng Regen Med 2012; 9:E229-38. [PMID: 23255506 DOI: 10.1002/term.1671] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2012] [Revised: 09/05/2012] [Accepted: 11/05/2012] [Indexed: 01/15/2023]
Abstract
Osteoarthritis (OA) is a common joint disease associated with articular cartilage degeneration. To improve the therapeutic options of OA, tissue engineering based on the use of mesenchymal stem cells (MSCs) has emerged. However, the presence of inflammatory cytokines, such as interleukin-1β (IL-1β), during chondrogenesis reduces the efficacy of cartilage engineering repair procedures by preventing chondrogenic differentiation. Previous studies have shown that electromagnetic fields (EMFs) stimulate anabolic processes in OA cartilage and limit IL-1β catabolic effects. We investigated the role of EMFs during chondrogenic differentiation of MSCs, isolated from bovine synovial fluid, in the absence and presence of IL-1β. Pellets of MSCs were differentiated for 3 and 5 weeks with transforming growth factor-β3 (TGFβ3), in the absence and presence of IL-1β and exposed or unexposed to EMFs. Biochemical, quantitative real-time RT-PCR and histological results showed that EMFs alone or in the presence of TGFβ3 play a limited role in promoting chondrogenic differentiation. Notably, in the presence of IL-1β and TGFβ3 a recovery of proteoglycan (PG) synthesis, PG content and aggrecan and type II collagen mRNA expression in the EMF-exposed compared to unexposed pellets was observed. Also, histological and immunohistochemical results showed an increase in staining for alcian blue, type II collagen and aggrecan in EMF-exposed pellets. In conclusion, this study shows a significant role of EMFs in counteracting the IL-1β-induced inhibition of chondrogenesis, suggesting EMFs as a therapeutic strategy for improving the clinical outcome of cartilage engineering repair procedures, based on the use of MSCs.
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Affiliation(s)
- Alessia Ongaro
- Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Italy.
| | - Agnese Pellati
- Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Italy
| | - Stefania Setti
- Laboratory of Clinical Biophysics, IGEA S.p.A, Carpi, Italy
| | | | | | - Milena Fini
- Laboratory of Preclinical and Surgical Studies, Research Institute Codivilla Putti, Rizzoli Orthopaedic Institute, Bologna, Italy
| | - Angelo Caruso
- Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Italy
| | - Monica De Mattei
- Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Italy
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