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Saiz Culma JJ, Guevara Morales JM, Hata Uribe YA, Garzón-Alvarado DA, Leal-Marin S, Glasmacher B, Vaca-González JJ. Effects of electric fields on the modulation of chondrocytes dynamics in gelatin scaffolds: a novel approach to optimize cartilage tissue engineering. JOURNAL OF BIOMATERIALS SCIENCE. POLYMER EDITION 2025:1-20. [PMID: 39998819 DOI: 10.1080/09205063.2025.2466971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Accepted: 02/07/2025] [Indexed: 02/27/2025]
Abstract
The treatment of degenerative pathologies affecting articular cartilage remains a significant clinical challenge. Non-invasive biophysical stimuli, such as electric fields, have demonstrated potential as therapeutic tools for cartilage tissue restoration. Previous studies have reported that electric fields enhance chondrocyte proliferation and the synthesis of key extracellular matrix components, such as glycosaminoglycans. However, inconsistencies in experimental designs have led to variable findings. This study examines the effects of capacitively coupled electric fields on chondrocytes cultured in gelatin hydrogels. Alternating voltages of 50 V (7.7 mV/cm) and 100 V (8.7 mV/cm) at a frequency of 60 kHz were applied for 21 days. Cell quantification and glycosaminoglycan analysis were performed on both stimulated and control samples. On day 7, exposure to the electric field resulted in a significant reduction in cell proliferation by 24.7% and 39.2% at 7.7 mV/cm and 8.7 mV/cm, respectively (p < 0.05). However, stimulation at 8.7 mV/cm led to a 35.7% increase in glycosaminoglycan synthesis compared to the control group (p < 0.05). These findings indicate that electric field stimulation can modulate the synthesis of essential extracellular matrix components, such as glycosaminoglycans, in hyaline cartilage. This highlights the potential of electric fields as a promising strategy to enhance outcomes in articular cartilage tissue engineering, particularly in hydrogel-based therapeutic approaches.
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Affiliation(s)
- Juan José Saiz Culma
- Biomimetics Laboratory, Biotechnology Institute, Universidad Nacional de Colombia, Bogotá, Colombia
- Numerical Methods and Modeling Research Group (GNUM), Universidad Nacional de Colombia, Bogotá, Colombia
| | | | - Yoshie Adriana Hata Uribe
- Biomimetics Laboratory, Biotechnology Institute, Universidad Nacional de Colombia, Bogotá, Colombia
- Numerical Methods and Modeling Research Group (GNUM), Universidad Nacional de Colombia, Bogotá, Colombia
| | - Diego Alexander Garzón-Alvarado
- Biomimetics Laboratory, Biotechnology Institute, Universidad Nacional de Colombia, Bogotá, Colombia
- Numerical Methods and Modeling Research Group (GNUM), Universidad Nacional de Colombia, Bogotá, Colombia
| | - Sara Leal-Marin
- Institute for Multiphase Processes, Leibniz University Hannover, Hannover, Germany
- Lower Saxony Center for Biomedical Engineering, Implant Research and Development (NIFE), Hannover, Germany
| | - Birgit Glasmacher
- Institute for Multiphase Processes, Leibniz University Hannover, Hannover, Germany
- Lower Saxony Center for Biomedical Engineering, Implant Research and Development (NIFE), Hannover, Germany
| | - Juan Jairo Vaca-González
- Biomimetics Laboratory, Biotechnology Institute, Universidad Nacional de Colombia, Bogotá, Colombia
- Numerical Methods and Modeling Research Group (GNUM), Universidad Nacional de Colombia, Bogotá, Colombia
- Grupo de investigación Biodiversidad para la Sociedad, Dirección Académica, Universidad Nacional de Colombia, Sede de La Paz, Cesar, Colombia
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Hou X, Zhang L, Chen Y, Liu Z, Zhao X, Lu B, Luo Y, Qu X, Musskaya O, Glazov I, Kulak AI, Chen F, Zhao J, Zhou Z, Zheng L. Photothermal switch by gallic acid-calcium grafts synthesized by coordination chemistry for sequential treatment of bone tumor and regeneration. Biomaterials 2025; 312:122724. [PMID: 39106818 DOI: 10.1016/j.biomaterials.2024.122724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 07/27/2024] [Accepted: 07/28/2024] [Indexed: 08/09/2024]
Abstract
The residual bone tumor and defects which is caused by surgical therapy of bone tumor is a major and important problem in clinicals. And the sequential treatment for irradiating residual tumor and repairing bone defects has wildly prospects. In this study, we developed a general modification strategy by gallic acid (GA)-assisted coordination chemistry to prepare black calcium-based materials, which combines the sequential photothermal therapy of bone tumor and bone defects. The GA modification endows the materials remarkable photothermal properties. Under the near-infrared (NIR) irradiation with different power densities, the black GA-modified bone matrix (GBM) did not merely display an excellent performance in eliminating bone tumor with high temperature, but showed a facile effect of the mild-heat stimulation to accelerate bone regeneration. GBM can efficiently regulate the microenvironments of bone regeneration in a spatial-temporal manner, including inflammation/immune response, vascularization and osteogenic differentiation. Meanwhile, the integrin/PI3K/Akt signaling pathway of bone marrow mesenchymal stem cells (BMSCs) was revealed to be involved in the effect of osteogenesis induced by the mild-heat stimulation. The outcome of this study not only provides a serial of new multifunctional biomaterials, but also demonstrates a general strategy for designing novel blacked calcium-based biomaterials with great potential for clinical use.
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Affiliation(s)
- Xiaodong Hou
- Center for Orthopedic Science and Translational Medicine, Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China; Department of Orthopedics, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, 650032, China
| | - Lei Zhang
- Center for Orthopedic Science and Translational Medicine, Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China
| | - Yixing Chen
- Center for Orthopedic Science and Translational Medicine, Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China
| | - Zhiqing Liu
- Center for Orthopedic Science and Translational Medicine, Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China
| | - Xinyu Zhao
- Center for Orthopedic Science and Translational Medicine, Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China
| | - Bingqiang Lu
- Center for Orthopedic Science and Translational Medicine, Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China
| | - Yiping Luo
- Center for Orthopedic Science and Translational Medicine, Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China
| | - Xinyu Qu
- Center for Orthopedic Science and Translational Medicine, Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China
| | - Olga Musskaya
- Institute of General and Inorganic Chemistry, National Academy of Sciences of Belarus, Surganova Str. 9, 220072, Minsk, Belarus
| | - Ilya Glazov
- Institute of General and Inorganic Chemistry, National Academy of Sciences of Belarus, Surganova Str. 9, 220072, Minsk, Belarus
| | - Anatoly I Kulak
- Institute of General and Inorganic Chemistry, National Academy of Sciences of Belarus, Surganova Str. 9, 220072, Minsk, Belarus
| | - Feng Chen
- Center for Orthopedic Science and Translational Medicine, Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
| | - Jing Zhao
- Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518107, China.
| | - Zifei Zhou
- Center for Orthopedic Science and Translational Medicine, Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
| | - Longpo Zheng
- Center for Orthopedic Science and Translational Medicine, Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China; Shanghai Trauma Emergency Center, Orthopedic Intelligent Minimally Invasive Diagnosis & Treatment Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
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3
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Kaadan A, Salati S, Setti S, Aaron R. Augmentation of Deficient Bone Healing by Pulsed Electromagnetic Fields-From Mechanisms to Clinical Outcomes. Bioengineering (Basel) 2024; 11:1223. [PMID: 39768041 PMCID: PMC11672986 DOI: 10.3390/bioengineering11121223] [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: 10/15/2024] [Revised: 11/19/2024] [Accepted: 11/26/2024] [Indexed: 01/11/2025] Open
Abstract
Pulsed Electromagnetic Fields (PEMF) are widely used, with excellent clinical outcomes. However, their mechanism of action has not yet been completely understood. The purpose of this review is to describe current observations on the mechanisms of PEMF, together with its clinical efficacy. Osteoblast responsiveness to PEMF is described on several scales, from the cell membrane to clinically relevant bone formation. PEMF has been shown to activate membrane adenosine receptors. The role of adenosine receptors in activating intracellular second messenger pathways, such as the canonical Wnt/β-catenin pathway and the mitogen-activated protein kinases (MAPK) pathway, is described. The responsiveness of osteoblasts and the synthesis of structural and signaling proteins constitute the role of PEMFs in promoting osteogenesis and bone matrix synthesis, and they are described. Multiple studies, ranging from observational and randomized to meta-analyses that investigate the clinical efficacy of PEMF, are described. This review presents a favorable conclusion on the clinical effects of PEMF while unlocking the "black box" of PEMF's mechanism of action, thus improving confidence in the clinical utility of PEMF in bone repair.
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Affiliation(s)
- Amr Kaadan
- Department of Orthopedic Surgery, Warren Alpert Medical School of Brown University, Providence, RI 02903, USA;
| | - Simona Salati
- Medical Division, Igea S.p.A, 41012 Carpi, Italy; (S.S.); (S.S.)
| | - Stefania Setti
- Medical Division, Igea S.p.A, 41012 Carpi, Italy; (S.S.); (S.S.)
| | - Roy Aaron
- Department of Orthopedic Surgery, Warren Alpert Medical School of Brown University, Providence, RI 02903, USA;
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Lucia U, Grisolia G, Ponzetto A, Deisboeck TS. Thermophysical Insights into the Anti-Inflammatory Potential of Magnetic Fields. Biomedicines 2024; 12:2534. [PMID: 39595100 PMCID: PMC11592124 DOI: 10.3390/biomedicines12112534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2024] [Revised: 10/31/2024] [Accepted: 11/03/2024] [Indexed: 11/28/2024] Open
Abstract
Background: Inflammation is caused by an excess of Sodium ions inside the cell. This generates a variation in the cell's membrane electric potential, becoming a steady state from a thermodynamic viewpoint. Methods: This paper introduces a thermodynamic approach to inflammation based on the fundamental role of the electric potential of the cell membrane, introducing an analysis of the effect of heat transfer related to the inflammation condition. Results: The direct proportionality between the reduction in temperature and the increase of Na+ outflow may ameliorate the inflammation cascade. Conclusions: Based on these ion fluxes, we suggest the consideration of a 'companion' electromagnetic therapeutic wave concept in support of the present anti-inflammatory treatment.
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Affiliation(s)
- Umberto Lucia
- Dipartimento Energia “Galileo Ferraris”, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy
| | - Giulia Grisolia
- Dipartimento di Ingegneria dell’Ambiente, del Territorio e delle Infrastrutture, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy
| | - Antonio Ponzetto
- Dipartimento di Scienze Mediche, Università di Torino, Corso Dogliotti 14, 10126 Torino, Italy
| | - Thomas S. Deisboeck
- Department of Radiology, Harvard-MIT Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, 149 Thirteenth Street, Charlestown, MA 02129, USA
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Zimmermann J, Farooqi AR, van Rienen U. Electrical stimulation for cartilage tissue engineering - A critical review from an engineer's perspective. Heliyon 2024; 10:e38112. [PMID: 39416819 PMCID: PMC11481755 DOI: 10.1016/j.heliyon.2024.e38112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 08/31/2024] [Accepted: 09/18/2024] [Indexed: 10/19/2024] Open
Abstract
Cartilage has a limited intrinsic healing capacity. Hence, cartilage degradation and lesions pose a huge clinical challenge, particularly in an ageing society. Osteoarthritis impacts a significant number of the population and requires the development of repair and tissue engineering methods for hyaline articular cartilage. In this context, electrical stimulation has been investigated for more than 50 years already. Yet, no well-established clinical therapy to treat osteoarthritis by means of electrical stimulation exists. We argue that one reason is the lack of replicability of electrical stimulation devices from a technical perspective together with lacking hypotheses of the biophysical mechanism. Hence, first, the electrical stimulation studies reported in the context of cartilage tissue engineering with a special focus on technical details are summarized. Then, an experimental and numerical approach is discussed to make the electrical stimulation experiments replicable. Finally, biophysical hypotheses have been reviewed on the interaction of electric fields and cells that are relevant for cartilage tissue engineering. With that, the aim is to inspire future research to enable clinical electrical stimulation therapies to fight osteoarthritis.
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Affiliation(s)
- Julius Zimmermann
- Institute of General Electrical Engineering, University of Rostock, 18051 Rostock, Germany
| | - Abdul Razzaq Farooqi
- Institute of General Electrical Engineering, University of Rostock, 18051 Rostock, Germany
- Department of Electronic Engineering, Faculty of Engineering, The Islamia University of Bahawalpur, 63100 Bahawalpur, Pakistan
| | - Ursula van Rienen
- Institute of General Electrical Engineering, University of Rostock, 18051 Rostock, Germany
- Department of Ageing of Individuals and Society, Interdisciplinary Faculty, University of Rostock, 18051 Rostock, Germany
- Department Life, Light & Matter, University of Rostock, 18051 Rostock, Germany
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6
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Luo M, Zeng X, Jiang L, Yi Q, Zhang L, Wang H, Huang J, Zhang Z, Tang S, Xiao Z. Effect of electrical stimulation on the fusion rate after spinal surgery: a systematic review and meta-analysis. Neurosurg Rev 2024; 47:618. [PMID: 39278993 DOI: 10.1007/s10143-024-02874-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 08/26/2024] [Accepted: 09/08/2024] [Indexed: 09/18/2024]
Abstract
Electrical stimulation is an important adjuvant therapy for spinal surgery, but whether receiving electrical stimulation can improve the fusion rate after spinal surgery is still controversial. The purpose of this study was to analyse and evaluate the effect of electrical stimulation on the fusion rate after spinal surgery. We systematically searched for related articles published in the PubMed, Embase and Cochrane Library databases on or before September 30, 2023. The odds ratio (OR) with 95% confidence interval (CI) and the fusion rates of the experimental group and the control group were calculated by a random-effects meta-analysis model. The analysis showed that receiving electrical stimulation significantly increased the probability of successful spinal fusion (OR 2.66 [95% CI 1.79-3.97]), and the average fusion rate of the electrical stimulation group (86.8%) was significantly greater than that of the control group (73.7%). The fusion rate in the direct current (DC) stimulation group was 2.33 times greater than that in the control group (OR 2.33 [95% CI 1.37-3.96]), and that in the pulsed electromagnetic field (PEMF) group was 2.60 times greater than that in the control group (OR 2.60 [95% CI 1.29-5.27]). Similarly, the fusion rate in the capacitive coupling (CC) electrical stimulation group was 3.44 times greater than that in the control group (OR 3.44 [95% CI 1.75-6.75]), indicating that regardless of the type of electrical stimulation, the fusion rate after spinal surgery improved to a certain extent. Electrical stimulation as an adjuvant therapy seems to improve the fusion rate after spinal surgery to a certain extent, but the specific effectiveness of this therapy needs to be further studied.
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Affiliation(s)
- Mingjiang Luo
- Department of Spine Surgery, Lishui Hospital of Wenzhou Medical University, Lishui People's Hospital, Lishui, Zhejiang, China
- Department of Spinal Surgery Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang City, 421000, Hunan Province, China
| | - Xin Zeng
- Department of Spine Surgery, Lishui Hospital of Wenzhou Medical University, Lishui People's Hospital, Lishui, Zhejiang, China
- Hengyang Medical School, University of South China, Hengyang City, Hunan Province, China
| | - Lingling Jiang
- Hengyang Medical School, University of South China, Hengyang City, Hunan Province, China
| | - Qilong Yi
- Hengyang Medical School, University of South China, Hengyang City, Hunan Province, China
| | - Lanxin Zhang
- Hengyang Medical School, University of South China, Hengyang City, Hunan Province, China
| | - Haoyun Wang
- Hengyang Medical School, University of South China, Hengyang City, Hunan Province, China
| | - Jinshan Huang
- Department of Spinal Surgery Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang City, 421000, Hunan Province, China
| | - Zihan Zhang
- Department of Spinal Surgery Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang City, 421000, Hunan Province, China
| | - Siliang Tang
- Department of Spinal Surgery Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang City, 421000, Hunan Province, China.
| | - Zhihong Xiao
- Department of Spine Surgery, Lishui Hospital of Wenzhou Medical University, Lishui People's Hospital, Lishui, Zhejiang, China.
- Department of Spinal Surgery Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang City, 421000, Hunan Province, China.
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Yu T, Wang J, Zhou Y, Ma C, Bai R, Huang C, Wang S, Liu K, Han B. Harnessing Engineered Extracellular Vesicles from Mesenchymal Stem Cells as Therapeutic Scaffolds for Bone‐Related Diseases. ADVANCED FUNCTIONAL MATERIALS 2024; 34. [DOI: 10.1002/adfm.202402861] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Indexed: 10/05/2024]
Abstract
AbstractMesenchymal stem cells (MSCs) play a crucial role in maintaining bone homeostasis and are extensively explored for cell therapy in various bone‐related diseases. In addition to direct cell therapy, the secretion of extracellular vesicles (EVs) by MSCs has emerged as a promising alternative approach. MSC‐derived EVs (MSC‐EVs) offer equivalent therapeutic efficacy to MSCs while mitigating potential risks. These EVs possess unique properties that enable them to traverse biological barriers and deliver bioactive cargos to target cells. Furthermore, by employing modification and engineering strategies, the therapeutic effects and tissue targeting specificity of MSC‐EVs can be further enhanced to meet specific therapeutic needs. In this review, the mechanisms and advantages of MSC‐EV therapy in diseased bone tissues are highlighted. Through simple isolation and modification techniques, MSC‐EV‐based biomaterials have demonstrated great promise for bone regeneration. Finally, future perspectives on MSC‐EV therapy are presented, envisioning the development of next‐generation regenerative materials and bioactive agents for clinical translation in the field of bone regeneration.
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Affiliation(s)
- Tingting Yu
- Department of Orthodontics Cranial‐Facial Growth and Development Center Peking University School and Hospital of Stomatology 22 Zhongguancun South Avenue, Haidian District Beijing 100081 P. R. China
- National Center for Stomatology National Clinical Research Center for Oral Diseases National Engineering Laboratory for Digital and Material Technology of Stomatology Beijing Key Laboratory for Digital Stomatology NMPA Key Laboratory for Dental Materials NHC Key Laboratory of Digital Stomatology Peking University School and Hospital of Stomatology 22 Zhongguancun South Avenue, Haidian District Beijing 100081 P. R. China
| | - Jingwei Wang
- Department of Orthodontics Cranial‐Facial Growth and Development Center Peking University School and Hospital of Stomatology 22 Zhongguancun South Avenue, Haidian District Beijing 100081 P. R. China
- National Center for Stomatology National Clinical Research Center for Oral Diseases National Engineering Laboratory for Digital and Material Technology of Stomatology Beijing Key Laboratory for Digital Stomatology NMPA Key Laboratory for Dental Materials NHC Key Laboratory of Digital Stomatology Peking University School and Hospital of Stomatology 22 Zhongguancun South Avenue, Haidian District Beijing 100081 P. R. China
| | - Yusai Zhou
- School of Materials Science and Engineering Beihang University Beijing 100191 P. R. China
| | - Chao Ma
- Engineering Research Center of Advanced Rare Earth Materials (Ministry of Education) Department of Chemistry Tsinghua University Beijing 100084 P. R. China
| | - Rushui Bai
- Department of Orthodontics Cranial‐Facial Growth and Development Center Peking University School and Hospital of Stomatology 22 Zhongguancun South Avenue, Haidian District Beijing 100081 P. R. China
- National Center for Stomatology National Clinical Research Center for Oral Diseases National Engineering Laboratory for Digital and Material Technology of Stomatology Beijing Key Laboratory for Digital Stomatology NMPA Key Laboratory for Dental Materials NHC Key Laboratory of Digital Stomatology Peking University School and Hospital of Stomatology 22 Zhongguancun South Avenue, Haidian District Beijing 100081 P. R. China
| | - Cancan Huang
- Department of Orthodontics Cranial‐Facial Growth and Development Center Peking University School and Hospital of Stomatology 22 Zhongguancun South Avenue, Haidian District Beijing 100081 P. R. China
- National Center for Stomatology National Clinical Research Center for Oral Diseases National Engineering Laboratory for Digital and Material Technology of Stomatology Beijing Key Laboratory for Digital Stomatology NMPA Key Laboratory for Dental Materials NHC Key Laboratory of Digital Stomatology Peking University School and Hospital of Stomatology 22 Zhongguancun South Avenue, Haidian District Beijing 100081 P. R. China
| | - Shidong Wang
- Musculoskeletal Tumor Center Peking University People's Hospital No.11 Xizhimen South St. Beijing 100044 P. R. China
| | - Kai Liu
- Engineering Research Center of Advanced Rare Earth Materials (Ministry of Education) Department of Chemistry Tsinghua University Beijing 100084 P. R. China
| | - Bing Han
- Department of Orthodontics Cranial‐Facial Growth and Development Center Peking University School and Hospital of Stomatology 22 Zhongguancun South Avenue, Haidian District Beijing 100081 P. R. China
- National Center for Stomatology National Clinical Research Center for Oral Diseases National Engineering Laboratory for Digital and Material Technology of Stomatology Beijing Key Laboratory for Digital Stomatology NMPA Key Laboratory for Dental Materials NHC Key Laboratory of Digital Stomatology Peking University School and Hospital of Stomatology 22 Zhongguancun South Avenue, Haidian District Beijing 100081 P. R. China
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Sun J, Xie W, Wu Y, Li Z, Li Y. Accelerated Bone Healing via Electrical Stimulation. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024:e2404190. [PMID: 39115981 DOI: 10.1002/advs.202404190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Revised: 07/01/2024] [Indexed: 08/10/2024]
Abstract
Piezoelectric effect produces an electrical signal when stress is applied to the bone. When the integrity of the bone is destroyed, the biopotential within the defect site is reduced and several physiological responses are initiated to facilitate healing. During the healing of the bone defect, the bioelectric potential returns to normal levels. Treatment of fractures that exceed innate regenerative capacity or exhibit delayed healing requires surgical intervention for bone reconstruction. For bone defects that cannot heal on their own, exogenous electric fields are used to assist in treatment. This paper reviews the effects of exogenous electrical stimulation on bone healing, including osteogenesis, angiogenesis, reduction in inflammation and effects on the peripheral nervous system. This paper also reviews novel electrical stimulation methods, such as small power supplies and nanogenerators, that have emerged in recent years. Finally, the challenges and future trends of using electrical stimulation therapy for accelerating bone healing are discussed.
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Affiliation(s)
- Jianfeng Sun
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Wenqing Xie
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Yuxiang Wu
- School of Kinesiology, Jianghan University, Wuhan, Hubei, 430056, China
| | - Zhou Li
- Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing, 101400, China
| | - Yusheng Li
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
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9
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Chen T, He Y, Xia S, Zhou F, Yuan X, Liu X. Evaluation of the effect of low-intensity pulsed ultrasound in pain and dysfunction for knee osteoarthritis: a double-blind, randomised controlled trial protocol. BMJ Open 2024; 14:e082108. [PMID: 38986557 PMCID: PMC11288152 DOI: 10.1136/bmjopen-2023-082108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 05/31/2024] [Indexed: 07/12/2024] Open
Abstract
INTRODUCTION Osteoarthritis (OA) is the most common joint disorder among musculoskeletal conditions. Non-surgical treatment is the standard therapy for knee OA (KOA). Ultrasound therapy is recommended for alleviating pain and dysfunction from OA, but high-quality scientific evidence for its effectiveness in OA treatment is still lacking.Therefore, we want to analyse whether combining conventional physical therapy with low-intensity pulsed ultrasound (LIPUS) can enhance the efficacy of conventional therapy, thus improving symptoms in patients with KOA. METHODS AND ANALYSIS This randomised controlled trial aims to recruit 200 patients diagnosed with KOA, aged 38 years or above, who meet the clinical diagnostic criteria for KOA. Patients will be randomly assigned in a 1:1 ratio to either a LIPUS treatment group or a sham ultrasound treatment control group. The 2-week treatment will consist of five sessions per week and evaluations will take place at baseline, on the day of the last intervention and 1 month post intervention. The main outcome measures will be the Western Ontario and McMaster Universities' scores. Secondary outcome indicators will be the Numerical Pain Rating Scale, the Lequesne scale, the time up and go test and the range of motion of the knee. An intention-to-treat analysis will be performed for dropouts and missing data. ETHICS AND DISSEMINATION The study was approved by the ethics committee of Shengjing Hospital of China Medical University (2023PS592K). Findings will be disseminated to participants and made available to peer-reviewed journals. TRIAL REGISTRATION NUMBER The trial was registered on the Chinese Clinical Trial Registry platform (chictr.org.cn) on 22 March 2023, with the registration ID ChiCTR2300069643.
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Affiliation(s)
- Tingxi Chen
- Department of Rehabilitation, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Yu He
- Department of Rehabilitation, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
- Department of Physical Medicine and Rehabilitation, Second Clinical College China Medical University, Shenyang, Liaoning, China
| | - Shenglin Xia
- Department of Rehabilitation, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Fenghua Zhou
- Department of Rehabilitation, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
- Department of Physical Medicine and Rehabilitation, Second Clinical College China Medical University, Shenyang, Liaoning, China
| | - Xiangnan Yuan
- Department of Rehabilitation, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
- Department of Physical Medicine and Rehabilitation, Second Clinical College China Medical University, Shenyang, Liaoning, China
| | - Xueyong Liu
- Department of Rehabilitation, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
- Department of Physical Medicine and Rehabilitation, Second Clinical College China Medical University, Shenyang, Liaoning, China
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10
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Luo S, Zhang C, Xiong W, Song Y, Wang Q, Zhang H, Guo S, Yang S, Liu H. Advances in electroactive biomaterials: Through the lens of electrical stimulation promoting bone regeneration strategy. J Orthop Translat 2024; 47:191-206. [PMID: 39040489 PMCID: PMC11261049 DOI: 10.1016/j.jot.2024.06.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 05/16/2024] [Accepted: 06/07/2024] [Indexed: 07/24/2024] Open
Abstract
The regenerative capacity of bone is indispensable for growth, given that accidental injury is almost inevitable. Bone regenerative capacity is relevant for the aging population globally and for the repair of large bone defects after osteotomy (e.g., following removal of malignant bone tumours). Among the many therapeutic modalities proposed to bone regeneration, electrical stimulation has attracted significant attention owing to its economic convenience and exceptional curative effects, and various electroactive biomaterials have emerged. This review summarizes the current knowledge and progress regarding electrical stimulation strategies for improving bone repair. Such strategies range from traditional methods of delivering electrical stimulation via electroconductive materials using external power sources to self-powered biomaterials, such as piezoelectric materials and nanogenerators. Electrical stimulation and osteogenesis are related via bone piezoelectricity. This review examines cell behaviour and the potential mechanisms of electrostimulation via electroactive biomaterials in bone healing, aiming to provide new insights regarding the mechanisms of bone regeneration using electroactive biomaterials. The translational potential of this article This review examines the roles of electroactive biomaterials in rehabilitating the electrical microenvironment to facilitate bone regeneration, addressing current progress in electrical biomaterials and the mechanisms whereby electrical cues mediate bone regeneration. Interactions between osteogenesis-related cells and electroactive biomaterials are summarized, leading to proposals regarding the use of electrical stimulation-based therapies to accelerate bone healing.
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Affiliation(s)
- Songyang Luo
- Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang, 110001, China
- Liaoning Provincial Key Laboratory of Oral Diseases, School and Hospital of Stomatology, China Medical University, Shenyang, 110001, China
| | - Chengshuo Zhang
- Hepatobiliary Surgery Department, The First Hospital of China Medical University, Shenyang, 110001, China
| | - Wei Xiong
- Department of Plastic Surgery, The First Hospital of Shihezi Medical University, Shihezi, 832000, China
| | - Yiping Song
- Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang, 110001, China
| | - Qiang Wang
- Liaoning Provincial Key Laboratory of Oral Diseases, School and Hospital of Stomatology, China Medical University, Shenyang, 110001, China
| | - Hangzhou Zhang
- Department of Orthopedics, The First Hospital of China Medical University, Shenyang Sports Medicine Clinical Medical Research Center, Shenyang, 110001, China
| | - Shu Guo
- Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang, 110001, China
| | - Shude Yang
- Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang, 110001, China
- Liaoning Provincial Key Laboratory of Oral Diseases, School and Hospital of Stomatology, China Medical University, Shenyang, 110001, China
| | - Huanye Liu
- Liaoning Provincial Key Laboratory of Oral Diseases, School and Hospital of Stomatology, China Medical University, Shenyang, 110001, China
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Quarta D, Grassi M, Lattanzi G, Gigante AP, D'Anca A, Potena D. Three predictive scores compared in a retrospective multicenter study of nonunion tibial shaft fracture. World J Orthop 2024; 15:560-569. [PMID: 38947264 PMCID: PMC11212531 DOI: 10.5312/wjo.v15.i6.560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 03/01/2024] [Accepted: 04/25/2024] [Indexed: 06/12/2024] Open
Abstract
BACKGROUND Delayed union, malunion, and nonunion are serious complications in the healing of fractures. Predicting the risk of nonunion before or after surgery is challenging. AIM To compare the most prevalent predictive scores of nonunion used in clinical practice to determine the most accurate score for predicting nonunion. METHODS We collected data from patients with tibial shaft fractures undergoing surgery from January 2016 to December 2020 in three different trauma hospitals. In this retrospective multicenter study, we considered only fractures treated with intramedullary nailing. We calculated the tibia FRACTure prediction healING days (FRACTING) score, Nonunion Risk Determination score, and Leeds-Genoa Nonunion Index (LEG-NUI) score at the time of definitive fixation. RESULTS Of the 130 patients enrolled, 89 (68.4%) healed within 9 months and were classified as union. The remaining patients (n = 41, 31.5%) healed after more than 9 months or underwent other surgical procedures and were classified as nonunion. After calculation of the three scores, LEG-NUI and FRACTING were the most accurate at predicting healing. CONCLUSION LEG-NUI and FRACTING showed the best performances by accurately predicting union and nonunion.
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Affiliation(s)
- Davide Quarta
- Clinical Orthopedics, Department of Clinical and Molecular Science, Università Politecnica Delle Marche, Ancona 60126, Italy
| | - Marco Grassi
- Clinical Orthopedics, Department of Clinical and Molecular Science, Università Politecnica Delle Marche, Ancona 60126, Italy
| | - Giuliano Lattanzi
- Clinical Orthopedics, Department of Clinical and Molecular Science, Università Politecnica Delle Marche, Ancona 60126, Italy
| | - Antonio Pompilio Gigante
- Clinical Orthopedics, Department of Clinical and Molecular Science, Università Politecnica Delle Marche, Ancona 60126, Italy
| | - Alessio D'Anca
- Department of Information and Engineering, Università Politecnica delle Marche, Ancona 60121, Italy
| | - Domenico Potena
- Department of Information and Engineering, Università Politecnica delle Marche, Ancona 60121, Italy
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Daou F, Masante B, Gabetti S, Mochi F, Putame G, Zenobi E, Scatena E, Dell'Atti F, Favero F, Leigheb M, Del Gaudio C, Bignardi C, Massai D, Cochis A, Rimondini L. Unraveling the transcriptome profile of pulsed electromagnetic field stimulation in bone regeneration using a bioreactor-based investigation platform. Bone 2024; 182:117065. [PMID: 38428556 DOI: 10.1016/j.bone.2024.117065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 02/07/2024] [Accepted: 02/26/2024] [Indexed: 03/03/2024]
Abstract
INTRODUCTION Human mesenchymal stem cells (hMSCs) sense and respond to biomechanical and biophysical stimuli, yet the involved signaling pathways are not fully identified. The clinical application of biophysical stimulation including pulsed electromagnetic field (PEMF) has gained momentum in musculoskeletal disorders and bone tissue engineering. METHODOLOGY We herein aim to explore the role of PEMF stimulation in bone regeneration by developing trabecular bone-like tissues, and then, culturing them under bone-like mechanical stimulation in an automated perfusion bioreactor combined with a custom-made PEMF stimulator. After selecting the optimal cell seeding and culture conditions for inspecting the effects of PEMF on hMSCs, transcriptomic studies were performed on cells cultured under direct perfusion with and without PEMF stimulation. RESULTS We were able to identify a set of signaling pathways and upstream regulators associated with PEMF stimulation and to distinguish those linked to bone regeneration. Our findings suggest that PEMF induces the immune potential of hMSCs by activating and inhibiting various immune-related pathways, such as macrophage classical activation and MSP-RON signaling in macrophages, respectively, while promoting angiogenesis and osteogenesis, which mimics the dynamic interplay of biological processes during bone healing. CONCLUSIONS Overall, the adopted bioreactor-based investigation platform can be used to investigate the impact of PEMF stimulation on bone regeneration.
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Affiliation(s)
- Farah Daou
- Dept. of Health Sciences, Center for Translational Research on Autoimmune and Allergic Diseases (CAAD), Università del Piemonte Orientale (UPO), Novara, Italy
| | - Beatrice Masante
- Dept. of Mechanical and Aerospace Engineering, PolitoBIOMed Lab, Politecnico di Torino, Turin, Italy; Interuniversity Center for the Promotion of the 3Rs Principles in Teaching and Research, Pisa, Italy
| | - Stefano Gabetti
- Dept. of Mechanical and Aerospace Engineering, PolitoBIOMed Lab, Politecnico di Torino, Turin, Italy; Interuniversity Center for the Promotion of the 3Rs Principles in Teaching and Research, Pisa, Italy
| | | | - Giovanni Putame
- Dept. of Mechanical and Aerospace Engineering, PolitoBIOMed Lab, Politecnico di Torino, Turin, Italy; Interuniversity Center for the Promotion of the 3Rs Principles in Teaching and Research, Pisa, Italy
| | - Eleonora Zenobi
- Hypatia Research Consortium, Rome, Italy; E. Amaldi Foundation, Rome, Italy
| | - Elisa Scatena
- Hypatia Research Consortium, Rome, Italy; E. Amaldi Foundation, Rome, Italy
| | - Federica Dell'Atti
- Dept. of Health Sciences, Center for Translational Research on Autoimmune and Allergic Diseases (CAAD), Università del Piemonte Orientale (UPO), Novara, Italy
| | - Francesco Favero
- Dept. of Health Sciences, Center for Translational Research on Autoimmune and Allergic Diseases (CAAD), Università del Piemonte Orientale (UPO), Novara, Italy
| | - Massimiliano Leigheb
- Dept. of Health Sciences, Center for Translational Research on Autoimmune and Allergic Diseases (CAAD), Università del Piemonte Orientale (UPO), Novara, Italy; Department of Orthopaedics and Traumatology, "Maggiore della Carità" Hospital, Novara, Italy
| | | | - Cristina Bignardi
- Dept. of Mechanical and Aerospace Engineering, PolitoBIOMed Lab, Politecnico di Torino, Turin, Italy; Interuniversity Center for the Promotion of the 3Rs Principles in Teaching and Research, Pisa, Italy
| | - Diana Massai
- Dept. of Mechanical and Aerospace Engineering, PolitoBIOMed Lab, Politecnico di Torino, Turin, Italy; Interuniversity Center for the Promotion of the 3Rs Principles in Teaching and Research, Pisa, Italy
| | - Andrea Cochis
- Dept. of Health Sciences, Center for Translational Research on Autoimmune and Allergic Diseases (CAAD), Università del Piemonte Orientale (UPO), Novara, Italy
| | - Lia Rimondini
- Dept. of Health Sciences, Center for Translational Research on Autoimmune and Allergic Diseases (CAAD), Università del Piemonte Orientale (UPO), Novara, Italy.
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Muraev AA, Manukyan GG, Salekh KM, Bonartsev AP, Volkov AV. Magnetic field application in bone tissue regeneration: issue current status and prospects for method development. RUDN JOURNAL OF MEDICINE 2024; 28:9-22. [DOI: 10.22363/2313-0245-2024-28-1-9-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2025] Open
Abstract
Relevance. Magnets have long been used to treat various diseases, especially in inflammatory processes. According to existing historical data, magnetotherapy was already used in ancient times by the Chinese, Egyptians and Greeks. Different magnetic field strengths affect cells in different ways, with medium-strength magnetic fields being the most widely used. The review presents a brief history and current state of the issue of using a magnetic field in bone tissue regeneration. Modern knowledge about the mechanisms of physiological and reparative regeneration, restoration of bone tissue is clarified, and modern areas of bone tissue engineering are considered, taking into account the characteristics of microcirculation and the effect of a magnetic field on the physiology of bone tissue and reparative regeneration. One of the key findings of the review is that the magnetic field improves bone tissue repair by influencing the metabolic behavior of cells. Studies show that magnetotherapy promotes the activation of cellular processes, accelerates the formation of new bone tissue and improves its quality. It is also noted that the magnetic field has a positive effect on microcirculation, improving the blood supply to tissues and facilitating a better supply of nutrients to the site of injury. This contributes to faster wound healing and early rehabilitation of patients. Conclusion. Magnetotherapy is one of the effective physical and rehabilitation methods of treatment that will become increasingly important in modern medicine. However, further research is needed to better understand the mechanisms of action of a magnetic field on bone tissue and to determine the optimal parameters for its application.
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Taghizadeh S, Tayebi L, Akbarzadeh M, Lohrasbi P, Savardashtaki A. Magnetic hydrogel applications in articular cartilage tissue engineering. J Biomed Mater Res A 2024; 112:260-275. [PMID: 37750666 DOI: 10.1002/jbm.a.37620] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 09/02/2023] [Accepted: 09/11/2023] [Indexed: 09/27/2023]
Abstract
Articular cartilage defects afflict millions of individuals worldwide, presenting a significant challenge due to the tissue's limited self-repair capability and anisotropic nature. Hydrogel-based biomaterials have emerged as promising candidates for scaffold production in artificial cartilage construction, owing to their water-rich composition, biocompatibility, and tunable properties. Nevertheless, conventional hydrogels typically lack the anisotropic structure inherent to natural cartilage, impeding their clinical and preclinical applications. Recent advancements in tissue engineering (TE) have introduced magnetically responsive hydrogels, a type of intelligent hydrogel that can be remotely controlled using an external magnetic field. These innovative materials offer a means to create the desired anisotropic architecture required for successful cartilage TE. In this review, we first explore conventional techniques employed for cartilage repair and subsequently delve into recent breakthroughs in the application and utilization of magnetic hydrogels across various aspects of articular cartilage TE.
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Affiliation(s)
- Saeed Taghizadeh
- Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
- Pharmaceutical Science Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Lobat Tayebi
- Marquette University School of Dentistry, Milwaukee, Wisconsin, USA
| | - Majid Akbarzadeh
- Department of Internal Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Parvin Lohrasbi
- Department of Reproductive Biology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amir Savardashtaki
- Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
- Infertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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Goncharov EN, Koval OA, Nikolaevich Bezuglov E, Engelgard M, Igorevich EI, Velentinovich Kotenko K, Encarnacion Ramirez MDJ, Montemurro N. Comparative Analysis of Stromal Vascular Fraction and Alternative Mechanisms in Bone Fracture Stimulation to Bridge the Gap between Nature and Technological Advancement: A Systematic Review. Biomedicines 2024; 12:342. [PMID: 38397944 PMCID: PMC10887176 DOI: 10.3390/biomedicines12020342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 01/26/2024] [Accepted: 01/30/2024] [Indexed: 02/25/2024] Open
Abstract
BACKGROUND Various stimulation methods, including electrical, ultrasound, mechanical, and biological interventions, are explored, each leveraging intricate cellular and molecular dynamics to expedite healing. The advent of stromal vascular fraction (SVF) marks a significant stride, offering multifarious benefits in bone healing, from enhanced bone formation to optimal vascular integration, drawing a harmonious balance between innate mechanisms and scientific advancements. METHODS This systematic review was conducted focusing on literature from 2016 to 2023 and encompassing various bone healing stimulation mechanisms like SVF, electrical, ultrasound, and mechanical stimulation. The extracted data underwent meticulous synthesis and analysis, emphasizing comparative evaluations of mechanisms, applications, and outcomes of each intervention. RESULTS The reviewed studies reveal the potential of SVF in bone fracture healing, with its regenerative and anti-inflammatory effects. The purification of SVF is crucial for safe therapeutic use. Characterization involves flow cytometry and microscopy. Studies show SVF's efficacy in bone regeneration, versatility in various contexts, and potential for clinical use. SVF appears superior to electrical, ultrasound, and mechanical stimulation, with low complications. CONCLUSIONS This review compares bone healing methods, including SVF. It provides valuable insights into SVF's potential for bone regeneration. However, due to limited human studies and potential bias, cautious interpretation is necessary. Further research is essential to validate these findings and determine the optimal SVF applications in bone healing.
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Affiliation(s)
| | | | | | - Mikhail Engelgard
- Petrovsky Russian Scientific Center of Surgery, 121359 Moscow, Russia
| | | | | | | | - Nicola Montemurro
- Department of Neurosurgery, Azienda Ospedaliero Universitaria Pisana (AOUP), 56100 Pisa, Italy
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Belluzzi E, Pozzuoli A, Ruggieri P. Musculoskeletal Diseases: From Molecular Basis to Therapy. Biomedicines 2023; 12:32. [PMID: 38255139 PMCID: PMC10813464 DOI: 10.3390/biomedicines12010032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Accepted: 12/20/2023] [Indexed: 01/24/2024] Open
Abstract
Musculoskeletal diseases (MSDs) comprise a plethora of different disorders (more than 150 conditions) affecting the locomotor system [...].
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Affiliation(s)
- Elisa Belluzzi
- Musculoskeletal Pathology and Oncology Laboratory, Department of Surgery, Oncology and Gastroenterology DiSCOG, University of Padova, Via Giustiniani 3, 35128 Padova, Italy;
- Orthopedics and Orthopedic Oncology, Department of Surgery, Oncology and Gastroenterology DiSCOG, University of Padova, Via Giustiniani 3, 35128 Padova, Italy
- Centre for Mechanics of Biological Materials, University of Padova, 35131 Padova, Italy
| | - Assunta Pozzuoli
- Musculoskeletal Pathology and Oncology Laboratory, Department of Surgery, Oncology and Gastroenterology DiSCOG, University of Padova, Via Giustiniani 3, 35128 Padova, Italy;
- Orthopedics and Orthopedic Oncology, Department of Surgery, Oncology and Gastroenterology DiSCOG, University of Padova, Via Giustiniani 3, 35128 Padova, Italy
- Centre for Mechanics of Biological Materials, University of Padova, 35131 Padova, Italy
| | - Pietro Ruggieri
- Orthopedics and Orthopedic Oncology, Department of Surgery, Oncology and Gastroenterology DiSCOG, University of Padova, Via Giustiniani 3, 35128 Padova, Italy
- Centre for Mechanics of Biological Materials, University of Padova, 35131 Padova, Italy
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Moura NB, Ferreira CL, Lima VCS, Nunes CMM, de Marco AC, Costa ALF, Lopes SLPC, Jardini MAN. Effect of the pulsed electromagnetic field in the repair of a calvaria critical bone defect in rats: cone beam computed tomographic and histomorphometric analysis.: PEMF in the repair of a calvaria critical bone defect: CBCT analyses. JOURNAL OF STOMATOLOGY, ORAL AND MAXILLOFACIAL SURGERY 2023; 124:101483. [PMID: 37100171 DOI: 10.1016/j.jormas.2023.101483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 04/18/2023] [Accepted: 04/21/2023] [Indexed: 04/28/2023]
Abstract
INTRODUCTION The present study evaluated the effect of two protocols of Pulsed Electromagnetic Field (PEMF) therapy on bone neoformation on calvaria critical defects in rats. MATERIAL & METHODS 96 rats were randomly divided into 3 groups: Control Group (CG; n=32); Test Group - PEMF 1 hour (TG1h; n=32) and Test Group - PEMF 3 hour (TG3h; n=32). A Critical-size Bone Defect (CSD) was surgically created in the calvaria of rats. The animals in the test groups were exposure to PEMF for 5 days a week. The animals were euthanized at 14, 21, 45 and 60 days. The specimens were processed for volume and texture (TAn) analysis, by Cone Beam Computed Tomography (CBCT) and histomorphometric analysis, RESULTS: Histomorphometric and volume analyses revealed that there was no statistically significant difference in the repair of bone defects between groups receiving PEMF therapy and CG. TAn revealed a statistically significant difference between the groups only for the entropy parameter, in which TG1h group presented a higher value compared to CG on 21 days. TG1h and TG3h did not accelerate bone repair in calvarial critical size defect and the parameters of PEMF should be considered. DISCUSSION This study showed that PEMF application on CSD in rats does not accelerate bone repair. Although literature showed a positive association in biostimulation on bone tissue with the parameters applied, studies with other PEMF parameters are essential to verify improving this study design.
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Affiliation(s)
- Nicole Bertonde Moura
- Graduate student of institute of Science and Technology of Sao Jose dos Campos, Universidade Estadual Paulista (Unesp), São José dos Campos, SP, Brazil
| | - Camila Lopes Ferreira
- Department of Diagnosis and Surgery, Institute of Science and Technology of Sao Jose dos Campos, Universidade Estadual Paulista (unesp), Sao Jose dos Campos, SP, Brazil
| | - Victória Clarada Silva Lima
- Graduate student of institute of Science and Technology of Sao Jose dos Campos, Universidade Estadual Paulista (Unesp), São José dos Campos, SP, Brazil
| | - Camilla Magnoni Moretto Nunes
- Department of Diagnosis and Surgery, Institute of Science and Technology of Sao Jose dos Campos, Universidade Estadual Paulista (unesp), Sao Jose dos Campos, SP, Brazil
| | - Andrea Carvalho de Marco
- Department of Diagnosis and Surgery, Institute of Science and Technology of Sao Jose dos Campos, Universidade Estadual Paulista (unesp), Sao Jose dos Campos, SP, Brazil
| | - André Luiz Ferreira Costa
- Postgraduate Program in Dentistry, Cruzeiro do Sul University (UNICSUL), Sao Paulo, Sao Paulo, Brazil
| | - Sérgio Lúcio Pereirade Castro Lopes
- Department of Diagnosis and Surgery, Institute of Science and Technology of Sao Jose dos Campos, Universidade Estadual Paulista (unesp), Sao Jose dos Campos, SP, Brazil
| | - Maria Aparecida Neves Jardini
- Department of Diagnosis and Surgery, Institute of Science and Technology of Sao Jose dos Campos, Universidade Estadual Paulista (unesp), Sao Jose dos Campos, SP, Brazil.
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Di Martino A, Villari E, Poluzzi R, Brunello M, Rossomando V, D’Agostino C, Ruta F, Faldini C. Role of biophysical stimulation in multimodal management of vertebral compression fractures. Comput Struct Biotechnol J 2023; 21:5650-5661. [PMID: 38047233 PMCID: PMC10692617 DOI: 10.1016/j.csbj.2023.11.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 11/10/2023] [Accepted: 11/10/2023] [Indexed: 12/05/2023] Open
Abstract
Raised life expectancy and aging of the general population are associated with an increased concern for fragility fractures due to factors such as osteoporosis, reduced bone density, and an higher risk of falls. Among these, the most frequent are vertebral compression fractures (VCF), which can be clinically occult. Once the diagnosis is made, generally thorough antero-posterior and lateral views of the affected spine at the radiographs, a comprehensive workup to assess the presence of a metabolic bone disease or secondary causes of osteoporosis and bone frailty is required. Treatment uses a multimodal management consisting of a combination of brace, pain management, bone metabolism evaluation, osteoporosis medication and has recently incorporated biophysical stimulation, a noninvasive technique that uses induced electric stimulation to improve bone recovery through the direct and indirect upregulation of bone morphogenic proteins, stimulating bone formation and remodeling. It contributes to the effectiveness of the therapy, promoting accelerated healing, supporting the reduction of bed rest and pain medications, improving patients' quality of life, and reducing the risk to undergo surgery in patients affected by VCFs. Therefore, the aim of this review is to outline the fundamental concepts of multimodal treatment for VCF, as well as the present function and significance of biophysical stimulation in the treatment of VCF patients.
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Affiliation(s)
- Alberto Di Martino
- 1st Orthopaedic and Traumatologic Department, IRCCS Istituto Ortopedico Rizzoli, Via G.B. Pupilli 1, 40136 Bologna, Italy
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy
| | - Eleonora Villari
- 1st Orthopaedic and Traumatologic Department, IRCCS Istituto Ortopedico Rizzoli, Via G.B. Pupilli 1, 40136 Bologna, Italy
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy
| | - Riccardo Poluzzi
- 1st Orthopaedic and Traumatologic Department, IRCCS Istituto Ortopedico Rizzoli, Via G.B. Pupilli 1, 40136 Bologna, Italy
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy
| | - Matteo Brunello
- 1st Orthopaedic and Traumatologic Department, IRCCS Istituto Ortopedico Rizzoli, Via G.B. Pupilli 1, 40136 Bologna, Italy
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy
| | - Valentino Rossomando
- 1st Orthopaedic and Traumatologic Department, IRCCS Istituto Ortopedico Rizzoli, Via G.B. Pupilli 1, 40136 Bologna, Italy
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy
| | - Claudio D’Agostino
- 1st Orthopaedic and Traumatologic Department, IRCCS Istituto Ortopedico Rizzoli, Via G.B. Pupilli 1, 40136 Bologna, Italy
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy
| | - Federico Ruta
- 1st Orthopaedic and Traumatologic Department, IRCCS Istituto Ortopedico Rizzoli, Via G.B. Pupilli 1, 40136 Bologna, Italy
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy
| | - Cesare Faldini
- 1st Orthopaedic and Traumatologic Department, IRCCS Istituto Ortopedico Rizzoli, Via G.B. Pupilli 1, 40136 Bologna, Italy
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy
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Huang L, Dong G, Peng J, Li T, Zou M, Hu K, Shu Y, Cheng T, Hao L. The role of exosomes and their enhancement strategies in the treatment of osteoarthritis. Hum Cell 2023; 36:1887-1900. [PMID: 37603220 DOI: 10.1007/s13577-023-00970-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Accepted: 08/12/2023] [Indexed: 08/22/2023]
Abstract
With the increasingly prominent problem of population aging, osteoarthritis (OA), which is closely related to aging, has become a serious illness affecting the lives and health of elderly individuals. However, effective treatments are still lacking. OA is typically considered a low-grade inflammatory state. The inflammatory infiltration of macrophages, neutrophils, T cells, and other cells is common in diseased joints. These cells create the inflammatory environment of OA and are involved in the onset and progression of the disease. Exosomes, a type of complex vesicle containing abundant RNA molecules and proteins, play a crucial role in the physiological and pathological processes of an organism. In comparison to other therapeutic methods such as stem cells, exosomes have distinct advantages of precise targeting and low immunogenicity. Moreover, research and techniques related to exosomes are more mature, indicating a promising future in disease treatment. Many studies have shown that the impact of exosomes on the inflammatory microenvironment directly or indirectly leads to the occurrence of various diseases. Furthermore, exosomes can be helpful in the management of illnesses. This article provides a comprehensive review and update on the research of exosomes, a type of extracellular vesicle, in the treatment of OA by modulating the inflammatory microenvironment. It also combines innovative studies on the modification of exosomes. In general, the application of exosomes in the treatment of OA has been validated, and the introduction of modified exosome technology holds potential for enhancing its therapeutic efficacy.
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Affiliation(s)
- Linzhen Huang
- Department of Orthopedics, Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China
- The Second Clinical Medical College, Nanchang University, Nanchang, 330006, China
| | - Ge Dong
- Department of Orthopedics, Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China
- The Second Clinical Medical College, Nanchang University, Nanchang, 330006, China
| | - Jie Peng
- Department of Orthopedics, Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China
- The Second Clinical Medical College, Nanchang University, Nanchang, 330006, China
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Ting Li
- Department of Orthopedics, Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China
- The Second Clinical Medical College, Nanchang University, Nanchang, 330006, China
| | - Mi Zou
- Department of Orthopedics, Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China
- The Second Clinical Medical College, Nanchang University, Nanchang, 330006, China
| | - Kaibo Hu
- Department of Orthopedics, Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China
- The Second Clinical Medical College, Nanchang University, Nanchang, 330006, China
| | - Yuan Shu
- Department of Orthopedics, Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China
- The Second Clinical Medical College, Nanchang University, Nanchang, 330006, China
| | - Tao Cheng
- Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai, China
| | - Liang Hao
- Department of Orthopedics, Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
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20
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Jia W, Zhou Z, Zhan W. Musculoskeletal Biomaterials: Stimulated and Synergized with Low Intensity Pulsed Ultrasound. J Funct Biomater 2023; 14:504. [PMID: 37888169 PMCID: PMC10607075 DOI: 10.3390/jfb14100504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Revised: 09/10/2023] [Accepted: 09/21/2023] [Indexed: 10/28/2023] Open
Abstract
Clinical biophysical stimulating strategies, which have significant effects on improving the function of organs or treating diseases by causing the salutary response of body, have shown many advantages, such as non-invasiveness, few side effects, and controllable treatment process. As a critical technique for stimulation, the low intensity pulsed ultrasound (LIPUS) has been explored in regulating osteogenesis, which has presented great promise in bone repair by delivering a combined effect with biomaterials. This review summarizes the musculoskeletal biomaterials that can be synergized with LIPUS for enhanced biomedical application, including bone regeneration, spinal fusion, osteonecrosis/osteolysis, cartilage repair, and nerve regeneration. Different types of biomaterials are categorized for summary and evaluation. In each subtype, the verified biological mechanisms are listed in a table or graphs to prove how LIPUS was effective in improving musculoskeletal tissue regeneration. Meanwhile, the acoustic excitation parameters of LIPUS that were promising to be effective for further musculoskeletal tissue engineering are discussed, as well as their limitations and some perspectives for future research. Overall, coupled with biomimetic scaffolds and platforms, LIPUS may be a powerful therapeutic approach to accelerate musculoskeletal tissue repair and even in other regenerative medicine applications.
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Affiliation(s)
- Wanru Jia
- Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;
| | - Zifei Zhou
- Department of Orthopedics, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Weiwei Zhan
- Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;
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21
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Abbas A, Khan Z, Veqar Z. Dose dependent effects of extracorporeal shockwave therapy on pain and function in osteonecrosis of femoral head: A systematic review. J Clin Orthop Trauma 2023; 45:102275. [PMID: 37927904 PMCID: PMC10624593 DOI: 10.1016/j.jcot.2023.102275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 09/11/2023] [Accepted: 10/21/2023] [Indexed: 11/07/2023] Open
Abstract
Purpose To investigate the effectiveness of different dosages of extracorporeal shockwave therapy (ESWT) on pain, function and radiographic outcomes in patients with osteonecrosis of femoral head (ONFH). Procedure The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta Analysis) guidelines were followed to conduct this review. The systematic literature search was done by using six different electronic databases include MEDLINE (assessed by Pubmed) CENTRAL (Cochrane Library Central Register of Controlled Trials), Web of Science, PEDro (Physiotherapy Evidence Database), Scopus and Science Direct. Retrospective and prospective cohort studies; case control study, randomized clinical trials were included. Screening conducted by two independent authors along with inclusion and exclusion criteria of included studies. The methodological quality assessment for cohort studies and randomized clinical trials was done by using Structured Effectiveness Quality Evaluation Scale (SEQES) and Newcastle-Ottawa Scale for case control study. Result Total 1410 articles were found from various databases. After duplicates removed 450 articles remained. Followed by title and abstract screening 53 articles eligible for full text reading, out of them 13 articles met the inclusion criteria and included in this review. Conclusion High energy flux densities of ESWT found to be more effective followed by low and moderate energy flux densities in earlier course of the disease compared to later stages in terms of pain relief, functional improvement and disease progression. Due to high variability among study design, ESWT dosages, patient characteristics and considering the paucity of well conducted studies, the present study cannot be conclusive.
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Affiliation(s)
- Ali Abbas
- Jamia Millia Islamia, Centre for Physiotherapy and Rehabilitation Sciences, New Delhi, 110025, India
| | - Zainy Khan
- Jamia Millia Islamia, Centre for Physiotherapy and Rehabilitation Sciences, New Delhi, 110025, India
| | - Zubia Veqar
- Jamia Millia Islamia, Centre for Physiotherapy and Rehabilitation Sciences, New Delhi, 110025, India
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22
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Han J, Ma Q, An Y, Wu F, Zhao Y, Wu G, Wang J. The current status of stimuli-responsive nanotechnologies on orthopedic titanium implant surfaces. J Nanobiotechnology 2023; 21:277. [PMID: 37596638 PMCID: PMC10439657 DOI: 10.1186/s12951-023-02017-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Accepted: 07/21/2023] [Indexed: 08/20/2023] Open
Abstract
With the continuous innovation and breakthrough of nanomedical technology, stimuli-responsive nanotechnology has been gradually applied to the surface modification of titanium implants to achieve brilliant antibacterial activity and promoted osteogenesis. Regarding to the different physiological and pathological microenvironment around implants before and after surgery, these surface nanomodifications are designed to respond to different stimuli and environmental changes in a timely, efficient, and specific way/manner. Here, we focus on the materials related to stimuli-responsive nanotechnology on titanium implant surface modification, including metals and their compounds, polymer materials and other materials. In addition, the mechanism of different response types is introduced according to different activation stimuli, including magnetic, electrical, photic, radio frequency and ultrasonic stimuli, pH and enzymatic stimuli (the internal stimuli). Meanwhile, the associated functions, potential applications and developing prospect were discussion.
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Affiliation(s)
- Jingyuan Han
- Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Oral Implants, School of Stomatology, The Fourth Military Medical University, Xi’an, 710032 China
- School of Stomatology, Heilongjiang Key Lab of Oral Biomedicine Materials and Clinical Application, Experimental Center for Stomatology Engineering, Jiamusi University, Jiamusi, 154007 China
| | - Qianli Ma
- Department of Biomaterials, Institute of Clinical Dentistry, University of Oslo, Geitmyrsveien, Oslo, 710455 Norway
| | - Yanxin An
- Department of General Surgery, The First Affiliated Hospital of Xi’an Medical University, Xi’an, China
| | - Fan Wu
- Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Oral Implants, School of Stomatology, The Fourth Military Medical University, Xi’an, 710032 China
- School of Stomatology, Heilongjiang Key Lab of Oral Biomedicine Materials and Clinical Application, Experimental Center for Stomatology Engineering, Jiamusi University, Jiamusi, 154007 China
| | - Yuqing Zhao
- Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Oral Implants, School of Stomatology, The Fourth Military Medical University, Xi’an, 710032 China
- School of Stomatology, Heilongjiang Key Lab of Oral Biomedicine Materials and Clinical Application, Experimental Center for Stomatology Engineering, Jiamusi University, Jiamusi, 154007 China
| | - Gaoyi Wu
- School of Stomatology, Heilongjiang Key Lab of Oral Biomedicine Materials and Clinical Application, Experimental Center for Stomatology Engineering, Jiamusi University, Jiamusi, 154007 China
| | - Jing Wang
- Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Oral Implants, School of Stomatology, The Fourth Military Medical University, Xi’an, 710032 China
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23
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de Sire A, Lippi L, Marotta N, Ferrillo M, Folli A, Turco A, Ammendolia A, Invernizzi M. Myths and truths on biophysics-based approach in rehabilitation of musculoskeletal disorders. Ther Adv Musculoskelet Dis 2023; 15:1759720X231183867. [PMID: 37484926 PMCID: PMC10359654 DOI: 10.1177/1759720x231183867] [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: 02/14/2023] [Accepted: 06/04/2023] [Indexed: 07/25/2023] Open
Abstract
Musculoskeletal disorders (MSD) are a crucial issue in current literature due to their impact on physical function, social, and economic costs. Rehabilitation plays a pivotal role in the therapeutic management of these disabling conditions with growing evidence underlining positive effects in improving functional outcomes. However, to date, several questions are still open about the mechanisms underpinning functional improvements while recent research is now focusing on a deeper understanding of the biophysical processes underpinning the macroscopical effects of these treatments. Thus, this narrative review aims at providing a comprehensive overview about the state of the art of biophysical dimensions of currently available treatments for MSD. PubMed, Scopus, CENTRAL, PEDro, and Web of Science were searched between March 2022 and October 2022 for in vitro and in vivo studies, clinical trials, systematic reviews, and meta-analysis addressing the issue of biophysics-based approach in rehabilitation of MSD. Our findings showed that a biophysical approach might be integrated into regenerative rehabilitation, aiming at enhancing regenerative processes by mechanical and biophysical stimuli. In addition, a biophysical-based approach has been proposed to improve knowledge about several instrumental physical therapies, including shock wave therapies, low-level laser therapy, ultrasound, short-wave diathermy, electrical stimulation, pulsed electromagnetic field, and vibration therapy. In accordance, emerging research is now focusing on the biophysical properties of several medical procedures to improve pain management in patients with MSD. Taken together, our results showed promising results of the integration of a biophysical-based approach in rehabilitation, albeit several limitations currently limit its implementation in routine clinical setting. Unfortunately, the state of the art is still inconclusive, and the low quality of clinical studies based on the biophysical approach did not provide clear treatment protocols. Further studies are needed to promote a precise rehabilitation approach targeting biological modification and enhancing the functional improvement of patients with MSDs.
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Affiliation(s)
| | | | - Nicola Marotta
- Division of Physical and Rehabilitative Medicine, Department of Experimental and Clinical Medicine, ‘Magna Graecia’ University, Catanzaro, Italy
- Research Center on Musculoskeletal Health, MusculoSkeletalHealth@UMG, University of Catanzaro ‘Magna Graecia’, Catanzaro, Italy
| | - Martina Ferrillo
- Department of Health Sciences, University of Catanzaro ‘Magna Graecia’, Catanzaro, Italy
| | - Arianna Folli
- Physical and Rehabilitative Medicine, Department of Health Sciences, University of Eastern Piedmont ‘A. Avogadro’, Novara, Italy
| | - Alessio Turco
- Physical and Rehabilitative Medicine, Department of Health Sciences, University of Eastern Piedmont ‘A. Avogadro’, Novara, Italy
| | - Antonio Ammendolia
- Physical and Rehabilitative Medicine Unit, Department of Medical and Surgical Sciences, University of Catanzaro ‘Magna Graecia’, Catanzaro, Italy
- Research Center on Musculoskeletal Health, MusculoSkeletalHealth@UMG, University of Catanzaro ‘Magna Graecia’, Catanzaro, Italy
| | - Marco Invernizzi
- Physical and Rehabilitative Medicine, Department of Health Sciences, University of Eastern Piedmont ‘A. Avogadro’, Novara, Italy
- Dipartimento Attività Integrate Ricerca e Innovazione (DAIRI), Translational Medicine, Azienda Ospedaliera SS, Alessandria, Italy
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24
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Flatscher J, Pavez Loriè E, Mittermayr R, Meznik P, Slezak P, Redl H, Slezak C. Pulsed Electromagnetic Fields (PEMF)-Physiological Response and Its Potential in Trauma Treatment. Int J Mol Sci 2023; 24:11239. [PMID: 37510998 PMCID: PMC10379303 DOI: 10.3390/ijms241411239] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Revised: 07/04/2023] [Accepted: 07/05/2023] [Indexed: 07/30/2023] Open
Abstract
Environmental biophysical interactions are recognized to play an essential part in the human biological processes associated with trauma recovery. Many studies over several decades have furthered our understanding of the effects that Pulsed Electromagnetic Fields (PEMF) have on the human body, as well as on cellular and biophysical systems. These investigations have been driven by the observed positive clinical effects of this non-invasive treatment on patients, mainly in orthopedics. Unfortunately, the diversity of the various study setups, with regard to physical parameters, molecular and cellular response, and clinical outcomes, has made it difficult to interpret and evaluate commonalities, which could, in turn, lead to finding an underlying mechanistic understanding of this treatment modality. In this review, we give a birds-eye view of the vast landscape of studies that have been published on PEMF, presenting the reader with a scaffolded summary of relevant literature starting from categorical literature reviews down to individual studies for future research studies and clinical use. We also highlight discrepancies within the many diverse study setups to find common reporting parameters that can lead to a better universal understanding of PEMF effects.
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Affiliation(s)
- Jonas Flatscher
- Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, 1200 Vienna, Austria
| | - Elizabeth Pavez Loriè
- Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, 1200 Vienna, Austria
| | | | - Paul Meznik
- AUVA Trauma Center Vienna-Meidling, 1120 Vienna, Austria
| | - Paul Slezak
- Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, 1200 Vienna, Austria
| | - Heinz Redl
- Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, 1200 Vienna, Austria
| | - Cyrill Slezak
- Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, 1200 Vienna, Austria
- Department of Physics, Utah Valley University, Orem, UT 84058, USA
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25
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Paolucci T, Pino V, Elsallabi O, Gallorini M, Pozzato G, Pozzato A, Lanuti P, Reis VM, Pesce M, Pantalone A, Buda R, Patruno A. Quantum Molecular Resonance Inhibits NLRP3 Inflammasome/Nitrosative Stress and Promotes M1 to M2 Macrophage Polarization: Potential Therapeutic Effect in Osteoarthritis Model In Vitro. Antioxidants (Basel) 2023; 12:1358. [PMID: 37507898 PMCID: PMC10376596 DOI: 10.3390/antiox12071358] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 06/22/2023] [Accepted: 06/23/2023] [Indexed: 07/30/2023] Open
Abstract
This study aimed to investigate the anti-inflammatory effects of Quantum Molecular Resonance (QMR) technology in an in vitro model of osteoarthritis-related inflammation. The study used THP-1-derived macrophages stimulated with lipopolysaccharide and hyaluronic acid fragments to induce the expression of inflammatory cytokines and nitrosative stress. QMR treatment inhibited COX-2 and iNOS protein expression and activity and reduced NF-κB activity. Furthermore, QMR treatment led to a significant reduction in peroxynitrite levels, reactive nitrogen species that can form during inflammatory conditions, and restored tyrosine nitration values to those similar to sham-exposed control cells. We also investigated the effect of QMR treatment on inflammasome activation and macrophage polarization in THP-1-derived macrophages. Results showed that QMR treatment significantly decreased NLRP3 and activated caspase-1 protein expression levels and downregulated IL-18 and IL-1β protein expression and secretion. Finally, our findings indicate that QMR treatment induces a switch in macrophage polarization from the M1 phenotype to the M2 phenotype.
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Affiliation(s)
- Teresa Paolucci
- Department of Oral, Medical and Biotechnological Sciences, Physical Medicine and Rehabilitation, University G. D'Annunzio, 66100 Chieti, Italy
| | - Vanessa Pino
- Department of Medicine and Aging Sciences, University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy
| | - Osama Elsallabi
- Department of Medicine and Aging Sciences, University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy
- Institute on the Biology of Aging and Metabolism and Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA
| | - Marialucia Gallorini
- Department of Pharmacy, University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy
| | | | | | - Paola Lanuti
- Department of Medicine and Aging Sciences, University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy
| | - Victor Machado Reis
- Research Centre in Sport Sciences, Health Sciences and Human Development, 5001-801 Vila Real, Portugal
| | - Mirko Pesce
- Department of Medicine and Aging Sciences, University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy
| | - Andrea Pantalone
- Department of Medicine and Aging Sciences, University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy
| | - Roberto Buda
- Department of Medicine and Aging Sciences, University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy
| | - Antonia Patruno
- Department of Medicine and Aging Sciences, University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy
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Moretti L, Bizzoca D, Geronimo A, Abbaticchio AM, Moretti FL, Carlet A, Fischetti F, Moretti B. Targeting Adenosine Signalling in Knee Chondropathy: The Combined Action of Polydeoxyribonucleotide and Pulsed Electromagnetic Fields: A Current Concept Review. Int J Mol Sci 2023; 24:10090. [PMID: 37373237 PMCID: PMC10298276 DOI: 10.3390/ijms241210090] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 05/16/2023] [Accepted: 05/30/2023] [Indexed: 06/29/2023] Open
Abstract
Chondropathy of the knee is one of the most frequent degenerative cartilage pathologies with advancing age. Scientific research has, in recent years, advanced new therapies that target adenosine A2 receptors, which play a significant role in human health against many disease states by activating different protective effects against cell sufferance and damage. Among these, it has been observed that intra-articular injections of polydeoxyribonucleotides (PDRN) and Pulsed Electromagnetic Fields (PEMF) can stimulate the adenosine signal, with significant regenerative and healing effects. This review aims to depict the role and therapeutic modulation of A2A receptors in knee chondropathy. Sixty articles aimed at providing data for our study were included in this review. The present paper highlights how intra-articular injections of PDRN create beneficial effects by reducing pain and improving functional clinical scores, thanks to their anti-inflammatory action and the important healing and regenerating power of the stimulation of cell growth, production of collagen, and the extracellular matrix. PEMF therapy is a valid option in the conservative treatment of different articular pathologies, including early OA, patellofemoral pain syndrome, spontaneous osteonecrosis of the knee (SONK), and in athletes. PEMF could also be used as a supporting therapy after an arthroscopic knee procedure total knee arthroplasty to reduce the post-operative inflammatory state. The proposal of new therapeutic approaches capable of targeting the adenosine signal, such as the intra-articular injection of PDRN and the use of PEMF, has shown excellent beneficial results compared to conventional treatments. These are presented as an extra weapon in the fight against knee chondropathy.
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Affiliation(s)
- Lorenzo Moretti
- Orthopaedics Unit—UOSD Vertebral Surgery, AOU Consorziale Policlinico, Piazza Giulio Cesare 11, 70124 Bari, Italy;
| | - Davide Bizzoca
- Orthopaedics Unit—UOSD Vertebral Surgery, AOU Consorziale Policlinico, Piazza Giulio Cesare 11, 70124 Bari, Italy;
- Ph.D. Course in Public Health, Clinical Medicine and Oncology, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, 70124 Bari, Italy
| | - Alessandro Geronimo
- Orthopaedics Unit, DiBraiN, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, 70124 Bari, Italy
| | | | - Francesco Luca Moretti
- National Centre for Chemicals, Cosmetic Products and Consumer Protection, National Institute of Health, 00161 Rome, Italy
| | - Arianna Carlet
- Orthopaedics Unit, DiBraiN, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, 70124 Bari, Italy
| | - Francesco Fischetti
- Departement DiBraiN, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, 70124 Bari, Italy
| | - Biagio Moretti
- Orthopaedics Unit, DiBraiN, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, 70124 Bari, Italy
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27
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Mazzotti A, Langone L, Artioli E, Zielli SO, Arceri A, Setti S, Leigheb M, Samaila EM, Faldini C. Applications and Future Perspective of Pulsed Electromagnetic Fields in Foot and Ankle Sport-Related Injuries. APPLIED SCIENCES 2023; 13:5807. [DOI: 10.3390/app13095807] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/23/2025]
Abstract
Foot and ankle injuries are common in many sports. One of the main athletes issues is the time for sport resumption after trauma. Recently, extensive efforts have been made to speed up the athletes’ return-to-sport and to prevent joint degeneration. Among the conservative treatment options, biophysical stimulation with pulsed electromagnetic fields (PEMFs) is listed. This narrative review aims to outline current applications of PEMFs in main foot and ankle sport-related injuries, in particular in the treatment of bone marrow edema, osteochondral defects, fractures, and nonunions. Despite further high-quality studies on foot and ankle injuries are needed, PEMFs seem to be a valid aid to enhance the endogenous osteogenesis, to resolve the bone marrow edema, to inhibit the joint inflammation, preserving articular cartilage degeneration, and to relieve pain.
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Affiliation(s)
- Antonio Mazzotti
- IRCCS Istituto Ortopedico Rizzoli, 1st Orthopaedics and Traumatology Clinic, University of Bologna, 40136 Bologna, Italy
- Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy
| | - Laura Langone
- IRCCS Istituto Ortopedico Rizzoli, 1st Orthopaedics and Traumatology Clinic, University of Bologna, 40136 Bologna, Italy
- Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy
| | - Elena Artioli
- IRCCS Istituto Ortopedico Rizzoli, 1st Orthopaedics and Traumatology Clinic, University of Bologna, 40136 Bologna, Italy
- Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy
| | - Simone Ottavio Zielli
- IRCCS Istituto Ortopedico Rizzoli, 1st Orthopaedics and Traumatology Clinic, University of Bologna, 40136 Bologna, Italy
- Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy
| | - Alberto Arceri
- IRCCS Istituto Ortopedico Rizzoli, 1st Orthopaedics and Traumatology Clinic, University of Bologna, 40136 Bologna, Italy
- Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy
| | | | - Massimiliano Leigheb
- Orthopaedics and Traumatology Unit, “Maggiore della Carità” Hospital, Department of Health Sciences, University of Piemonte Orientale, 28100 Novara, Italy
| | - Elena Manuela Samaila
- Department of Orthopedics and Trauma Surgery, University of Verona, Surgical Center “P. Confortini”, P.le A. Stefani, 1, 37126 Verona, Italy
| | - Cesare Faldini
- IRCCS Istituto Ortopedico Rizzoli, 1st Orthopaedics and Traumatology Clinic, University of Bologna, 40136 Bologna, Italy
- Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy
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28
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Kreller T, Zimmermann J, van Rienen U, Boccaccini AR, Jonitz-Heincke A, Detsch R. Alternating electric field stimulation: Phenotype analysis and osteoclast activity of differentiated RAW 264.7 macrophages on hydroxyapatite-coated Ti6Al4V surfaces and their crosstalk with MC3T3-E1 pre-osteoblasts. BIOMATERIALS ADVANCES 2023; 146:213285. [PMID: 36640524 DOI: 10.1016/j.bioadv.2023.213285] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 12/21/2022] [Accepted: 01/06/2023] [Indexed: 01/11/2023]
Affiliation(s)
- T Kreller
- Institute of Biomaterials, Department of Materials Science and Engineering, Friedrich Alexander-University Erlangen-Nuremberg, 91058 Erlangen, Germany
| | - J Zimmermann
- Institute of General Electrical Engineering, University of Rostock, 18051 Rostock, Germany
| | - U van Rienen
- Institute of General Electrical Engineering, University of Rostock, 18051 Rostock, Germany; Department Life, Light and Matter, University of Rostock, 18051 Rostock, Germany; Department Ageing of Individuals and Society, University of Rostock, 18051 Rostock, Germany
| | - A R Boccaccini
- Institute of Biomaterials, Department of Materials Science and Engineering, Friedrich Alexander-University Erlangen-Nuremberg, 91058 Erlangen, Germany
| | - A Jonitz-Heincke
- Research Laboratory for Biomechanics and Implant Technology, Department of Orthopedics, Rostock University Medical Center, 18057 Rostock, Germany
| | - R Detsch
- Institute of Biomaterials, Department of Materials Science and Engineering, Friedrich Alexander-University Erlangen-Nuremberg, 91058 Erlangen, Germany.
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29
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Factor S, Druckmann I, Atlan F, Rosenblatt Y, Tordjman D, Krespi R, Kazum E, Pritsch T, Eisenberg G. The Effects of Novel Pulsed Electromagnetic Field Therapy Device on Acute Distal Radius Fractures: A Prospective, Double-Blind, Sham-Controlled, Randomized Pilot Study. J Clin Med 2023; 12:jcm12051866. [PMID: 36902653 PMCID: PMC10003714 DOI: 10.3390/jcm12051866] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 02/20/2023] [Accepted: 02/22/2023] [Indexed: 03/03/2023] Open
Abstract
BACKGROUND this pilot study aimed at determining whether the application of a novel new method of generating pulsed electromagnetic field (PEMF), the Fracture Healing Patch (FHP), accelerates the healing of acute distal radius fractures (DRF) when compared to a sham treatment. METHODS 41 patients with DRFs treated with cast immobilization were included. Patients were allocated to a PEMF group (n = 20) or a control (sham) group (n = 21). All patients were assessed with regard to functional and radiological outcomes (X-rays and CT scans) at 2, 4, 6 and 12 weeks. RESULTS fractures treated with active PEMF demonstrated significantly higher extent of union at 4 weeks as assessed by CT (76% vs. 58%, p = 0.02). SF12 mean physical score was significantly higher in PEMF treated group (47 vs. 36, p = 0.005). Time to cast removal was significantly shorter in PEMF treated patients, 33 ± 5.9 days in PEMF vs. 39.8 ± 7.4 days in sham group (p = 0.002). CONCLUSION early addition of PEMF treatment may accelerate bone healing which could lead to a shorter cast immobilization, thus allowing an earlier return to daily life activities and work. There were no complications related to the PEMF device (FHP).
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Affiliation(s)
- Shai Factor
- Division of Orthopedic Surgery, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6423906, Israel
- Correspondence: ; Tel.: +972-52-7360753; Fax: +972-74-7219810
| | - Ido Druckmann
- Division of Radiology, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6423906, Israel
| | - Franck Atlan
- Division of Orthopedic Surgery, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6423906, Israel
| | - Yishai Rosenblatt
- Division of Orthopedic Surgery, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6423906, Israel
| | - Daniel Tordjman
- Division of Orthopedic Surgery, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6423906, Israel
| | - Raphael Krespi
- Division of Orthopedic Surgery, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6423906, Israel
| | - Efi Kazum
- Division of Orthopedic Surgery, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6423906, Israel
| | - Tamir Pritsch
- Division of Orthopedic Surgery, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6423906, Israel
| | - Gilad Eisenberg
- Division of Orthopedic Surgery, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6423906, Israel
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Littman J, Aaron RK. Stimulation of Chondrogenesis in a Developmental Model of Endochondral Bone Formation by Pulsed Electromagnetic Fields. Int J Mol Sci 2023; 24:3275. [PMID: 36834690 PMCID: PMC9967535 DOI: 10.3390/ijms24043275] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 01/30/2023] [Accepted: 02/01/2023] [Indexed: 02/10/2023] Open
Abstract
Notable characteristics of the skeleton are its responsiveness to physical stimuli and its ability to remodel secondary to changing biophysical environments and thereby fulfill its physiological roles of stability and movement. Bone and cartilage cells have many mechanisms to sense physical cues and activate a variety of genes to synthesize structural molecules to remodel their extracellular matrix and soluble molecules for paracrine signaling. This review describes the response of a developmental model of endochondral bone formation which is translationally relevant to embryogenesis, growth, and repair to an externally applied pulsed electromagnetic field (PEMF). The use of a PEMF allows for the exploration of morphogenesis in the absence of distracting stimuli such as mechanical load and fluid flow. The response of the system is described in terms of the cell differentiation and extracellular matrix synthesis in chondrogenesis. Emphasis is placed upon dosimetry of the applied physical stimulus and some of the mechanisms of tissue response through a developmental process of maturation. PEMFs are used clinically for bone repair and have other potential clinical applications. These features of tissue response and signal dosimetry can be extrapolated to the design of clinically optimal stimulation.
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Affiliation(s)
| | - Roy K. Aaron
- Department of Orthopedic Surgery, Warren Alpert Medical School of Brown University, Providence, RI 02903, USA
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Hong JE, Lee CG, Hwang S, Kim J, Jo M, Kang DH, Yoo SH, Kim WS, Lee Y, Rhee KJ. Pulsed Electromagnetic Field (PEMF) Treatment Ameliorates Murine Model of Collagen-Induced Arthritis. Int J Mol Sci 2023; 24:ijms24021137. [PMID: 36674651 PMCID: PMC9862561 DOI: 10.3390/ijms24021137] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Revised: 12/24/2022] [Accepted: 01/04/2023] [Indexed: 01/11/2023] Open
Abstract
Rheumatoid arthritis (RA) is an autoimmune disease of the joint synovial membranes. RA is difficult to prevent or treat; however, blocking proinflammatory cytokines is a general therapeutic strategy. Pulsed electromagnetic field (PEMF) is reported to alleviate RA's inflammatory response and is being studied as a non-invasive physical therapy. In this current study, PEMF decreased paw inflammation in a collagen-induced arthritis (CIA) murine model. PEMF treatment at 10 Hz was more effective in ameliorating arthritis than at 75 Hz. In the PEMF-treated CIA group, the gross inflammation score and cartilage destruction were lower than in the untreated CIA group. The CIA group treated with PEMF also showed lower serum levels of IL-1β but not IL-6, IL-17, or TNF-α. Serum levels of total anti-type II collagen IgG and IgG subclasses (IgG1, IgG2a, and IgG2b) remained unchanged. In contrast, tissue protein levels of IL-1β, IL-6, TNF-α, receptor activator of nuclear factor kappa-Β (RANK), RANK ligand (RANKL), IL-6 receptor (IL-6R), and TNF-α receptor1 (TNFR1) were all lower in the ankle joints of the PEMF-treated CIA group compared with the CIA group. The results of this study suggest that PEMF treatment can preserve joint morphology cartilage and delay the occurrence of CIA. PEMF has potential as an effective adjuvant therapy that can suppress the progression of RA.
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Affiliation(s)
- Ju-Eun Hong
- Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE Campus, Wonju 26493, Republic of Korea
| | - Chang-Gun Lee
- Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE Campus, Wonju 26493, Republic of Korea
- Department of Medical Genetics, Ajou University School of Medicine, Suwon 16499, Republic of Korea
| | - Soonjae Hwang
- Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE Campus, Wonju 26493, Republic of Korea
- Department of Biochemistry, Lee Gil Ya Cancer and Diabetes Institute, GAIHST, Gachon University College of Medicine, Incheon 21999, Republic of Korea
| | - Junyoung Kim
- Department of Biomedical Engineering, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE Campus, Wonju 26493, Republic of Korea
| | - Minjeong Jo
- Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE Campus, Wonju 26493, Republic of Korea
- Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea
| | - Da-Hye Kang
- Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE Campus, Wonju 26493, Republic of Korea
| | - Sang-Hyeon Yoo
- Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE Campus, Wonju 26493, Republic of Korea
| | - Woo-Seung Kim
- Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE Campus, Wonju 26493, Republic of Korea
| | - Yongheum Lee
- Department of Biomedical Engineering, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE Campus, Wonju 26493, Republic of Korea
| | - Ki-Jong Rhee
- Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE Campus, Wonju 26493, Republic of Korea
- Correspondence: ; Tel.: +82-33-760-2445; Fax: +82-33-760-2195
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Zhao Z, Liu J, Weir MD, Schneider A, Ma T, Oates TW, Xu HHK, Zhang K, Bai Y. Periodontal ligament stem cell-based bioactive constructs for bone tissue engineering. Front Bioeng Biotechnol 2022; 10:1071472. [PMID: 36532583 PMCID: PMC9755356 DOI: 10.3389/fbioe.2022.1071472] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Accepted: 11/17/2022] [Indexed: 09/29/2023] Open
Abstract
Objectives: Stem cell-based tissue engineering approaches are promising for bone repair and regeneration. Periodontal ligament stem cells (PDLSCs) are a promising cell source for tissue engineering, especially for maxillofacial bone and periodontal regeneration. Many studies have shown potent results via PDLSCs in bone regeneration. In this review, we describe recent cutting-edge researches on PDLSC-based bone regeneration and periodontal tissue regeneration. Data and sources: An extensive search of the literature for papers related to PDLSCs-based bioactive constructs for bone tissue engineering was made on the databases of PubMed, Medline and Google Scholar. The papers were selected by three independent calibrated reviewers. Results: Multiple types of materials and scaffolds have been combined with PDLSCs, involving xeno genic bone graft, calcium phosphate materials and polymers. These PDLSC-based constructs exhibit the potential for bone and periodontal tissue regeneration. In addition, various osteo inductive agents and strategies have been applied with PDLSCs, including drugs, biologics, gene therapy, physical stimulation, scaffold modification, cell sheets and co-culture. Conclusoin: This review article demonstrates the great potential of PDLSCs-based bioactive constructs as a promising approach for bone and periodontal tissue regeneration.
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Affiliation(s)
- Zeqing Zhao
- Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, China
| | - Jin Liu
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an Jiaotong University, Xi’an, China
| | - Michael D. Weir
- Biomaterials and Tissue Engineering Division, Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD, United States
| | - Abraham Schneider
- Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, Baltimore, MD, United States
| | - Tao Ma
- Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, Baltimore, MD, United States
| | - Thomas W. Oates
- Biomaterials and Tissue Engineering Division, Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD, United States
| | - Hockin H. K. Xu
- Biomaterials and Tissue Engineering Division, Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD, United States
- Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, United States
- Center for Stem Cell Biology and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Ke Zhang
- Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, China
| | - Yuxing Bai
- Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, China
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Safavi AS, Sendera A, Haghighipour N, Banas-Zabczyk A. The Role of Low-Frequency Electromagnetic Fields on Mesenchymal Stem Cells Differentiation: A Systematic Review. Tissue Eng Regen Med 2022; 19:1147-1160. [PMID: 36042129 PMCID: PMC9679119 DOI: 10.1007/s13770-022-00473-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 06/09/2022] [Accepted: 06/19/2022] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND Low-frequency electromagnetic fields (EMFs) influence biological processes. This present study was aimed at the scientific literature on the use of EMFs in the mesenchymal stem cell differentiation process. MATERIALS AND METHODS The electronic search was carried out in PubMed and Web of Science, a database with a combination of the sinusoidal and pulsed low- and extremely low-frequency electromagnetic fields stimulation and mesenchymal stem cells differentiation, considering the period of publication until December 2021. The literature search identified 118 references in PubMed and Web of Science of which 46 articles were selected, respectively, according to the eligibility requirements. CONCLUSION The analysis of research indicated that EMFs are an easy-to-apply and practical way in cell therapy and tissue engineering when regulation of stem cells is required. Studies have shown that EMFs have positive effects on stem cell differentiation, accelerating its process regardless of the parameters and type of stem cells. However, the exact amplitude, frequency, duration of the electrical field, and application method remain elusive and need more study in future work.
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Affiliation(s)
- Atiyeh Sadat Safavi
- National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran
- Department of Biomaterials and Tissue Engineering, School of Advanced Technologies in Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Anna Sendera
- Department of Biology, Institute of Medical Sciences, Medical College of Rzeszow University, University of Rzeszów, Rzeszow, Poland
| | | | - Agnieszka Banas-Zabczyk
- Department of Biology, Institute of Medical Sciences, Medical College of Rzeszow University, University of Rzeszów, Rzeszow, Poland.
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Caliogna L, Bina V, Brancato AM, Gastaldi G, Annunziata S, Mosconi M, Grassi FA, Benazzo F, Pasta G. The Role of PEMFs on Bone Healing: An In Vitro Study. Int J Mol Sci 2022; 23:14298. [PMID: 36430775 PMCID: PMC9693979 DOI: 10.3390/ijms232214298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 11/10/2022] [Accepted: 11/16/2022] [Indexed: 11/19/2022] Open
Abstract
Bone responses to pulsed electromagnetic fields (PEMFs) have been extensively studied by using devices that expose bone cells to PEMFs to stimulate extracellular matrix (ECM) synthesis for bone and cartilage repair. The aim of this work was to highlight in which bone healing phase PEMFs exert their action. Specifically, we evaluated the effects of PEMFs both on human adipose mesenchymal stem cells (hASCs) and on primary human osteoblasts (hOBs) by testing gene and protein expression of early bone markers (on hASCs) and the synthesis of late bone-specific proteins (on hOBs) as markers of bone remodeling. Our results indicate that PEMFs seem to exert their action on bone formation, acting on osteogenic precursors (hASCs) and inducing the commitment towards the differentiation pathways, unlike mature and terminally differentiated cells (hOBs), which are known to resist homeostasis perturbation more and seem to be much less responsive than mesenchymal stem cells. Understanding the role of PEMFs on bone regenerative processes provides important details for their clinical application.
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Affiliation(s)
- Laura Caliogna
- Orthopedics and Traumatology Clinic, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy
| | - Valentina Bina
- Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy
| | - Alice Maria Brancato
- Orthopedics and Traumatology Clinic, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy
| | - Giulia Gastaldi
- Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy
- Centre for Health Technologies, University of Pavia, 27100 Pavia, Italy
| | - Salvatore Annunziata
- Orthopedics and Traumatology Clinic, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy
| | - Mario Mosconi
- Orthopedics and Traumatology Clinic, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy
| | - Federico Alberto Grassi
- Orthopedics and Traumatology Clinic, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy
- Centre for Health Technologies, University of Pavia, 27100 Pavia, Italy
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy
| | - Francesco Benazzo
- Sezione di Chirurgia Protesica ad Indirizzo Robotico-Unità di Traumatologia dello Sport, U.O. Ortopedia e Traumatologia Fondazione Poliambulanza, 25124 Brescia, Italy
| | - Gianluigi Pasta
- Orthopedics and Traumatology Clinic, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy
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Vilela FB, Silva ES, de Lourdes Noronha Motta Melo M, Oliveira RMP, Capellato P, Sachs D. Polymeric Orthosis with Electromagnetic Stimulator Controlled by Mobile Application for Bone Fracture Healing: Evaluation of Design Concepts for Medical Use. MATERIALS (BASEL, SWITZERLAND) 2022; 15:8141. [PMID: 36431627 PMCID: PMC9698363 DOI: 10.3390/ma15228141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 10/28/2022] [Accepted: 11/02/2022] [Indexed: 06/16/2023]
Abstract
Background: The occurrence of bone fractures is increasing worldwide, mainly due to the health problems that follow the aging population. The use of additive manufacturing and electrical stimulators can be applied for bioactive achievements in bone healing. However, such technologies are difficult to be transferred to medical practice. This work aims to develop an orthosis with a combined magnetic field (CFM) electrostimulator that demonstrates concepts and design aspects that facilitate its use in a real scenario. Methods: A 3D-printed orthosis made of two meshes was manufactured using PLA for outer mechanical stabilization mesh and TPU for inner fixation mesh to avoid mobilization. A CFM stimulator of reduced dimension controlled by a mobile application was coupled onto the orthosis. The design concepts were evaluated by health professionals and their resistance to chemical agents commonly used in daily activities were tested. Their thermal, chemical and electrical properties were also characterized. Results: No degradation was observed after exposure to chemical agents. The CMF achieved proper intensity (20-40 µT). The thermal analysis indicated its appropriate use for being modelled during clinical assessment. Conclusion: An orthosis with a coupled electrostimulator that works with a combined magnetic field and is controlled by mobile application was developed, and it has advantageous characteristics when compared to traditional techniques for application in real medical environments.
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Affiliation(s)
- Filipe Bueno Vilela
- Centre for Studies and Innovation in Biofunctional Advanced Materials, Institute of Physics and Chemistry, Unifei-Federal University of Itajubá, Av. BPS, 1303, Itajubá 37500-903, MG, Brazil
| | - Eduardo Serafim Silva
- Centre for Studies and Innovation in Biofunctional Advanced Materials, Institute of Physics and Chemistry, Unifei-Federal University of Itajubá, Av. BPS, 1303, Itajubá 37500-903, MG, Brazil
| | | | - Rochelly Mariana Pedroso Oliveira
- Centre for Studies and Innovation in Biofunctional Advanced Materials, Institute of Physics and Chemistry, Unifei-Federal University of Itajubá, Av. BPS, 1303, Itajubá 37500-903, MG, Brazil
| | - Patricia Capellato
- Centre for Studies and Innovation in Biofunctional Advanced Materials, Institute of Physics and Chemistry, Unifei-Federal University of Itajubá, Av. BPS, 1303, Itajubá 37500-903, MG, Brazil
| | - Daniela Sachs
- Centre for Studies and Innovation in Biofunctional Advanced Materials, Institute of Physics and Chemistry, Unifei-Federal University of Itajubá, Av. BPS, 1303, Itajubá 37500-903, MG, Brazil
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De Francesco F, Gravina P, Varagona S, Setti S, Gigante A, Riccio M. Biophysical Stimulation in Delayed Fracture Healing of Hand Phalanx: A Radiographic Evaluation. Biomedicines 2022; 10:biomedicines10102519. [PMID: 36289781 PMCID: PMC9599654 DOI: 10.3390/biomedicines10102519] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 09/30/2022] [Accepted: 10/01/2022] [Indexed: 11/16/2022] Open
Abstract
Phalangeal fractures are common events among the upper limbs accounting for 10% of all human body fractures. Fracture complete healing process may persevere several months or years. Most phalangeal fractures present favorable union within 3 to 6 weeks. In the literature, biophysical stimulation has yielded favorable outcomes in the treatment of hand fractures. A survey involving hospitals in the US reported the use of biophysical stimulation (72%) in relation to nonhealing fractures at three months after trauma. A noninvasive procedure such as biophysical stimulation may be preferential prior to consideration of invasive procedures. In this retrospective study, we analyzed 80 phalangeal fractures, 43 of which did not show any radiographic sign of healing 30 days after surgery; on radiograms, we calculated radiographic data and the total active motion (TAM) for clinical comparison. All radiographic images were evaluated using Adobe Photoshop CS3 (version 10.0, Adobe Systems Inc., San Jose, CA, USA). We calculated the index of relative bone healing each month after surgery starting from 30 days, which was considered as T1, and followed up for a total of 6 months after stimulation (T6) with better results in stimulated groups. We concluded that prompt administration of biophysical stimulation supports fracture healing and yields an important improvement in the union rate compared with nontreatment. Above all, our patients experienced less injury-related distress between the fracture and repair period, which consequently reduced immobilization time, envisaging an early rehabilitation interval, with a better patient hand outcome.
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Affiliation(s)
- Francesco De Francesco
- Department of Reconstructive Surgery and Hand Surgery, Azienda Ospedaliera Universitaria delle Marche, Via Conca, 71, 60126 Ancona, Italy
- Correspondence: ; Tel.: +39-071-5963945; Fax: +39-071-5965297
| | - Pasquale Gravina
- Department of Reconstructive Surgery and Hand Surgery, Azienda Ospedaliera Universitaria delle Marche, Via Conca, 71, 60126 Ancona, Italy
- Clinical Orthopedics, Polytechnic University of Marche, Via Conca, 71, 60126 Ancona, Italy
| | - Stefano Varagona
- Clinical Orthopedics, Polytechnic University of Marche, Via Conca, 71, 60126 Ancona, Italy
| | - Stefania Setti
- IGEA SpA, Clinical Biophysics, Via Parmenide, 10/A, 41012 Carpi, Italy
| | - Antonio Gigante
- Clinical Orthopedics, Polytechnic University of Marche, Via Conca, 71, 60126 Ancona, Italy
| | - Michele Riccio
- Department of Reconstructive Surgery and Hand Surgery, Azienda Ospedaliera Universitaria delle Marche, Via Conca, 71, 60126 Ancona, Italy
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D'Ambrosi R, Ursino C, Setti S, Scelsi M, Ursino N. Pulsed electromagnetic fields improve pain management and clinical outcomes after medial unicompartmental knee arthroplasty: A prospective randomised controlled trial. J ISAKOS 2022; 7:105-112. [PMID: 35623611 DOI: 10.1016/j.jisako.2022.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 05/10/2022] [Accepted: 05/15/2022] [Indexed: 01/15/2023]
Abstract
BACKGROUND To assess pain relief and clinical outcomes in patients undergoing unicompartmental knee arthroplasty (UKA) stimulated with pulsed electromagnetic fields (PEMFs) compared to a control group. METHODS A prospective randomised controlled trial (RCT) was performed in which 72 patients undergoing medial UKA were randomised into a control group or an experimental PEMFs group. The patients allocated to the experimental group were instructed to use PEMFs for 4 h per day for 60 days. They were evaluated before a surgery and then during the time points corresponding to 1 month, 2 months, 6 months, 12 months, and 36 months after the surgery. No placebo group was included in the RCT. Clinical assessment included the Visual Analogue Scale (VAS) for pain, Oxford Knee Score (OKS), the Short Form 36 (SF-36) health survey questionnaire, and joint swelling. During each follow-up visit, the consumption of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) was recorded. RESULTS The VAS decreased on follow-up visits in both the groups; a statistically significant difference between the groups was observed during the 6 (p = 0.0297), 12 (p = 0.0003), and 36 months (p = 0.0333) follow-ups in favour of the PEMFs group. One month after UKA, the percentages of patients using NSAIDs in the PEMFs and control group were 71% and 92%, respectively (p = 0.0320). At the 2 months point, 15% of the patients in the PEMFs group used NSAIDs compared to 39% in the control group (p = 0.0317). The objective knee girth evaluation showed a statistically significant difference at 6 (p = 0.0204), 12 (p = 0.0005), and 36 (p = 0.0005) months with improved values observed in the PEMFs group. The subjective assessment of the swelling demonstrated a statistically significant difference at 2 (p = 0.0073), 6 (p = 0.0006), 12 (p = 0.0001), and 36 (p = 0.0011) months with better values noted in the PEMFs group. Last, the OKS result was significant higher in the experimental group during all the follow-ups (1mth: p = 0.0295; 2mths: p = 0.0012; 6mths: p = 0.0001; 12mths: p < 0.0001; 36mths: p = 0.0061). CONCLUSIONS The use of PEMFs leads to significant pain relief, better clinical improvement, and lower NSAIDs consumption after medial UKA when compared to the control group. LEVEL OF EVIDENCE II.
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Affiliation(s)
- Riccardo D'Ambrosi
- IRCCS Istituto Ortopedico Galeazzi, Milan, Italy; Università degli Studi di Milano, Dipartimento di Scienze Biomediche per la Salute, Milan, Italy.
| | - Chiara Ursino
- IRCCS Policlinico San Martino, Genova - Clinica Ortopedica, Genova, Italy.
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Pulsed Electrical Stimulation Affects Osteoblast Adhesion and Calcium Ion Signaling. Cells 2022; 11:cells11172650. [PMID: 36078058 PMCID: PMC9454840 DOI: 10.3390/cells11172650] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 08/18/2022] [Accepted: 08/23/2022] [Indexed: 11/17/2022] Open
Abstract
An extensive research field in regenerative medicine is electrical stimulation (ES) and its impact on tissue and cells. The mechanism of action of ES, particularly the role of electrical parameters like intensity, frequency, and duration of the electric field, is not yet fully understood. Human MG-63 osteoblasts were electrically stimulated for 10 min with a commercially available multi-channel system (IonOptix). We generated alternating current (AC) electrical fields with a voltage of 1 or 5 V and frequencies of 7.9 or 20 Hz, respectively. To exclude liquid-mediated effects, we characterized the AC-stimulated culture medium. AC stimulation did not change the medium’s pH, temperature, and oxygen content. The H2O2 level was comparable with the unstimulated samples except at 5 V_7.9 Hz, where a significant increase in H2O2 was found within the first 30 min. Pulsed electrical stimulation was beneficial for the process of attachment and initial adhesion of suspended osteoblasts. At the same time, the intracellular Ca2+ level was enhanced and highest for 20 Hz stimulated cells with 1 and 5 V, respectively. In addition, increased Ca2+ mobilization after an additional trigger (ATP) was detected at these parameters. New knowledge was provided on why electrical stimulation contributes to cell activation in bone tissue regeneration.
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Evaluation of Microstructure and Mechanical Properties of a Ti10Mo8Nb Alloy for Biomedical Applications. METALS 2022. [DOI: 10.3390/met12071065] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
The growth of the elderly population is urging for more suitable biomaterials to allow the performance of better surgical and implant procedures and accelerate the patient’s healing because the elderly are more vulnerable to orthopedic and dental problems. β-phase Ti alloys can improve the mechanical properties of implants by reducing their elastic modulus and, consequently, the effects of stress shielding within bones. Therefore, the objective of this article is to study a novel ternary β-phase alloy of Ti10Mo8Nb produced by an electric arc furnace and rotary forge. The microstructure and mechanical properties of the Ti10Mo8Nb alloy were investigated in order to evaluate its suitability for biomedical applications and compare its characteristics with those present in Ti-alloys commerced or widely researched for prosthetic purposes. A tensile test, Vickers microhardness test, use of microstructure of optical microscopy for examination of microstructure, X-ray diffraction and hemolysis analysis were carried out. Thus, the Ti10Mo8Nb alloy showed suitable properties for biomedical applications, as well as having the potential to reduce the possibility to occur stress shielding after prosthetic implantations, especially for orthopedics and dentistry.
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Kuzu TE, Öztürk K, Gürgan CA, Üşümez A, Yay A, Göktepe Ö. Effect of Photobiomodulation Therapy on Peri-Implant Bone Healing in Extra-Short Implants in a Rabbit Model: A Pilot Study. Photobiomodul Photomed Laser Surg 2022; 40:402-409. [PMID: 35749706 DOI: 10.1089/photob.2021.0098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Objective: To evaluate the effects of photobiomodulation therapy (PBMT) at distinct energy levels on peri-implant bone healing in extra-short implants in a experimental rabbit model. Background: The effect of PBMT on peri-implant bone healing in short implants remains unclear. This explored the effect of PBMT on extra-short implants in terms of bone-implant contact (BIC) length and rate, and implant stability quotient (ISQ). Methods: Fifteen white New Zealand rabbits were randomly divided into five groups. In all groups, extra-short implants (3.5 × 4 mm; Nucleoss T6, İzmir/Turkey) were placed in both tibias of the rabbits. PBMT was performed in four groups (group 1, 5 J/cm2; group 2, 10 J/cm2; group 3, 20 J/cm2; and group 4, 25 J/cm2); no PBMT was performed in the control group. On the 30th day, the rabbits were sacrificed and peri-implant tissue samples were obtained to determine the BIC length and BIC rate. Implant stability levels were measured by resonance frequency analysis using the Osstell penguin device and were determined as ISQ values on the 1st and 30th days of the study. Results: PBMT significantly increased the BIC length and BIC rate in groups 3 and 4 (p < 0.001). For the ISQ values, there were significant differences between the 1st and 30th day (p < 0.001). On the 30th day, the ISQ values were significantly higher in groups 3 and 4 compared with the remaining groups (p < 0.001). Conclusions: In this study, PBMT improved peri-implant bone healing through increase in BIC length, BIC rate, and ISQ parameter values in extra-short implants.
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Affiliation(s)
- Turan Emre Kuzu
- Department of Periodontology, Faculty of Dentistry, Nuh Naci Yazgan University, Kayseri, Turkey
| | - Kübra Öztürk
- Department of Oral and Maxillofacial Surgery, and Faculty of Dentistry, Nuh Naci Yazgan University, Kayseri, Turkey
| | - Cem A Gürgan
- Department of Periodontology, Faculty of Dentistry, Nuh Naci Yazgan University, Kayseri, Turkey
| | - Aslihan Üşümez
- Department of Prosthodontics, Dental Plus Dental Clinic, İstanbul, Turkey
| | - Arzu Yay
- Department of Histology and Embryology, Faculty of Medicine, Erciyes University, Kayseri, Turkey
| | - Özge Göktepe
- Department of Histology and Embryology, Erciyes University, Kayseri, Turkey
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41
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Liu N, Zheng C, Wang Q, Huang Z. Treatment of non-traumatic avascular necrosis of the femoral head (Review). Exp Ther Med 2022; 23:321. [PMID: 35386618 PMCID: PMC8972838 DOI: 10.3892/etm.2022.11250] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Accepted: 01/26/2022] [Indexed: 11/06/2022] Open
Abstract
Non-traumatic osteonecrosis of the femoral head is the main cause of disability in young individuals and incurs major health care expenditure. The lifestyle changes in recent years, especially increased use of hormones and alcohol consumption, has greatly increased the incidence of femoral head necrosis. The underlying causes and risk factors of osteonecrosis of the femoral head are increasingly being elucidated, which has led to the development of novel surgical and non-surgical treatment options. Although the main goal of any treatment method is prevention and delaying the progression of disease, there is no common consensus on the most suitable method of treatment. The present review discussed the latest developments in the etiology and treatment methods for femoral head necrosis.
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Affiliation(s)
- Ning Liu
- Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
| | | | - Qinglong Wang
- Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
| | - Zhipeng Huang
- Department of Orthopedics, The Second Affiliated Hospital of Air Force Military Medical University, Xi'an, Shaanxi 710000, P.R. China
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42
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Liu Z, Liu Q, Guo H, Liang J, Zhang Y. Overview of Physical and Pharmacological Therapy in Enhancing Bone Regeneration Formation During Distraction Osteogenesis. Front Cell Dev Biol 2022; 10:837430. [PMID: 35573673 PMCID: PMC9096102 DOI: 10.3389/fcell.2022.837430] [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: 12/16/2021] [Accepted: 04/14/2022] [Indexed: 11/13/2022] Open
Abstract
Distraction osteogenesis (DO) is a kind of bone regeneration technology. The principle is to incise the cortical bone and apply continuous and stable distraction force to the fractured end of the cortical bone, thereby promoting the proliferation of osteoblastic cells in the tension microenvironment and stimulating new bone formation. However, the long consolidation course of DO presumably lead to several complications such as infection, fracture, scar formation, delayed union and malunion. Therefore, it is of clinical significance to reduce the long treatment duration. The current treatment strategy to promote osteogenesis in DO includes gene, growth factor, stem-cell, physical and pharmacological therapies. Among these methods, pharmacological and physical therapies are considered as safe, economical, convenience and effective. Recently, several physical and pharmacological therapies have been demonstrated with a decent ability to enhance bone regeneration during DO. In this review, we have comprehensively summarized the latest evidence for physical (Photonic, Waves, Gas, Mechanical, Electrical and Electromagnetic stimulation) and pharmacological (Bisphosphonates, Hormone, Metal compounds, Biologics, Chinese medicine, etc) therapies in DO. These evidences will bring novel and significant information for the bone healing during DO in the future.
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Affiliation(s)
- Ze Liu
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Qi Liu
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Hongbin Guo
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Jieyu Liang
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Yi Zhang
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
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43
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Low-Intensity Pulsed Ultrasound in the Treatment of Nonunions and Fresh Fractures: A Case Series. TRAUMA CARE 2022. [DOI: 10.3390/traumacare2020014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
It is estimated that approximately 5% to 10% of fractures will evolve into nonunions. Nonunions have a significant impact on patient quality of life and on socioeconomic costs. Low-intensity pulsed ultrasound (LIPUS) is a non-invasive therapy widely used within the orthopedic community to accelerate the healing of fresh fractures, to minimize delayed healing, and to promote healing of nonunions. In this case series, 46 nonunions and 19 fresh fractures were treated with LIPUS for at least three months or until fracture healing. Bone healing was assessed both at a radiological and a functional level. Of the nonunions healed, 89% had a mean healing time of 89 ± 53 days. In the group of fresh fractures, the healing percentage was 95% with a mean healing time of 46 ± 28 days. LIPUS treatment is proven to be safe and well tolerated; there were no adverse events related to the use of the device, even in the presence of internal fixations and infections. LIPUS therapy should be considered a low-risk option both as an adjunct to surgery or as a standalone therapy in the management of nonunion and fresh fractures.
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Pettersen E, Anderson J, Ortiz-Catalan M. Electrical stimulation to promote osseointegration of bone anchoring implants: a topical review. J Neuroeng Rehabil 2022; 19:31. [PMID: 35313892 PMCID: PMC8939223 DOI: 10.1186/s12984-022-01005-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Accepted: 03/01/2022] [Indexed: 01/22/2023] Open
Abstract
Electrical stimulation has shown to be a promising approach for promoting osseointegration in bone anchoring implants, where osseointegration defines the biological bonding between the implant surface and bone tissue. Bone-anchored implants are used in the rehabilitation of hearing and limb loss, and extensively in edentulous patients. Inadequate osseointegration is one of the major factors of implant failure that could be prevented by accelerating or enhancing the osseointegration process by artificial means. In this article, we reviewed the efforts to enhance the biofunctionality at the bone-implant interface with electrical stimulation using the implant as an electrode. We reviewed articles describing different electrode configurations, power sources, and waveform-dependent stimulation parameters tested in various in vitro and in vivo models. In total 55 English-language and peer-reviewed publications were identified until April 2020 using PubMed, Google Scholar, and the Chalmers University of Technology Library discovery system using the keywords: osseointegration, electrical stimulation, direct current and titanium implant. Thirteen of those publications were within the scope of this review. We reviewed and compared studies from the last 45 years and found nonuniform protocols with disparities in cell type and animal model, implant location, experimental timeline, implant material, evaluation assays, and type of electrical stimulation. The reporting of stimulation parameters was also found to be inconsistent and incomplete throughout the literature. Studies using in vitro models showed that osteoblasts were sensitive to the magnitude of the electric field and duration of exposure, and such variables similarly affected bone quantity around implants in in vivo investigations. Most studies showed benefits of electrical stimulation in the underlying processes leading to osseointegration, and therefore we found the idea of promoting osseointegration by using electric fields to be supported by the available evidence. However, such an effect has not been demonstrated conclusively nor optimally in humans. We found that optimal stimulation parameters have not been thoroughly investigated and this remains an important step towards the clinical translation of this concept. In addition, there is a need for reporting standards to enable meta-analysis for evidence-based treatments.
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Affiliation(s)
- Emily Pettersen
- Center for Bionics and Pain Research, Mölndal, Sweden.,Department of Electrical Engineering, Chalmers University of Technology, Gothenburg, Sweden.,Center for Advanced Reconstruction of Extremities (C.A.R.E.), Sahlgrenska University Hospital, Mölndal, Sweden
| | - Jenna Anderson
- Center for Bionics and Pain Research, Mölndal, Sweden.,Center for Advanced Reconstruction of Extremities (C.A.R.E.), Sahlgrenska University Hospital, Mölndal, Sweden
| | - Max Ortiz-Catalan
- Center for Bionics and Pain Research, Mölndal, Sweden. .,Department of Electrical Engineering, Chalmers University of Technology, Gothenburg, Sweden. .,Department of Orthopaedics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
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45
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Numerical study on the effect of capacitively coupled electrical stimulation on biological cells considering model uncertainties. Sci Rep 2022; 12:4744. [PMID: 35304501 PMCID: PMC8933463 DOI: 10.1038/s41598-022-08279-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 03/03/2022] [Indexed: 11/08/2022] Open
Abstract
Electrical stimulation of biological samples such as tissues and cell cultures attracts growing attention due to its capability of enhancing cell activity, proliferation, and differentiation. Eventually, a profound knowledge of the underlying mechanisms paves the way for innovative therapeutic devices. Capacitive coupling is one option of delivering electric fields to biological samples that has advantages regarding biocompatibility. However, its biological mechanism of interaction is not well understood. Experimental findings could be related to voltage-gated channels, which are triggered by changes of the transmembrane potential. Numerical simulations by the finite element method provide a possibility to estimate the transmembrane potential. Since a full resolution of the cell membrane within a macroscopic model would lead to prohibitively expensive models, we suggest the adaptation of an approximate finite element method. Starting from a basic 2.5D model, the chosen method is validated and applied to realistic experimental situations. To understand the influence of the dielectric properties on the modelling outcome, uncertainty quantification techniques are employed. A frequency-dependent influence of the uncertain dielectric properties of the cell membrane on the modelling outcome is revealed. This may have practical implications for future experimental studies. Our methodology can be easily adapted for computational studies relying on experimental data.
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46
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Pulsed Electro-Magnetic Field (PEMF) Effect on Bone Healing in Animal Models: A Review of Its Efficacy Related to Different Type of Damage. BIOLOGY 2022; 11:biology11030402. [PMID: 35336776 PMCID: PMC8945722 DOI: 10.3390/biology11030402] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 02/18/2022] [Accepted: 03/03/2022] [Indexed: 11/17/2022]
Abstract
Simple Summary Pulsed electromagnetic fields (PEMFs) are a type of biophysical stimulation that has been shown to be effective in improving bone regeneration and preventing bone loss. Their use dates back to the 1970s, but a gold standard treatment protocol has not yet been defined. PEMF efficacy relies on the generation of biopotentials, which activate several molecular pathways. There is currently no clear understanding of the effects on bone healing and, in addition, there are several animal models relevant to this issue. Therefore, drawing guidelines and conclusions from the analysis of the studies is difficult. In vivo investigations on PEMF stimulation are reviewed in this paper, focusing on molecular and morphological improvements in bone. Currently, there is little knowledge about the biological mechanism of PEMF and its effect on bone healing. This is due to the variability of crucial characteristics of electro-magnetic fields, such as amplitude and exposure frequency, which may influence the type of biological response. Furthermore, a different responsiveness of cells involved in the bone healing process is documented. Heterogeneous setting parameters and different outcome measures are considered in various animal models. Therefore, achieving comparable results is difficult. Abstract Biophysical energies are a versatile tool to stimulate tissues by generating biopotentials. In particular, pulsed electromagnetic field (PEMF) stimulation has intrigued researchers since the 1970s. To date, many investigations have been carried out in vivo, but a gold standard treatment protocol has not yet been defined. The main obstacles are represented by the complex setting of PEMF characteristics, the variety of animal models (including direct and indirect bone damage) and the lack of a complete understanding of the molecular pathways involved. In the present review the main studies about PEMF stimulation in animal models with bone impairment were reviewed. PEMF signal characteristics were investigated, as well as their effect on molecular pathways and osseous morphological features. We believe that this review might be a useful starting point for a prospective study in a clinical setting. Consistent evidence from the literature suggests a potential beneficial role of PEMF in clinical practice. Nevertheless, the wide variability of selected parameters (frequency, duration, and amplitude) and the heterogeneity of applied protocols make it difficult to draw certain conclusions about PEMF effectiveness in clinical implementation to promote bone healing. Deepening the knowledge regarding the most consistent results reported in literature to date, we believe that this review may be a useful starting point to propose standardized experimental guidelines. This might provide a solid base for further controlled trials, to investigate PEMF efficacy in bone damage conditions during routine clinical practice.
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Cao L, Tong Y, Wang X, Zhang Q, Qi Y, Zhou C, Yu X, Wu Y, Miao X. Effect of Amniotic Membrane/Collagen-Based Scaffolds on the Chondrogenic Differentiation of Adipose-Derived Stem Cells and Cartilage Repair. Front Cell Dev Biol 2021; 9:647166. [PMID: 34900977 PMCID: PMC8657407 DOI: 10.3389/fcell.2021.647166] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Accepted: 10/20/2021] [Indexed: 11/24/2022] Open
Abstract
Objectives: Repairing articular cartilage damage is challenging. Clinically, tissue engineering technology is used to induce stem cell differentiation and proliferation on biological scaffolds to repair defective joints. However, no ideal biological scaffolds have been identified. This study investigated the effects of amniotic membrane/collagen scaffolds on the differentiation of adipose-derived stem cells (ADSCs) and articular cartilage repair. Methods: Adipose tissue of New Zealand rabbits was excised, and ADSCs were isolated and induced for differentiation. An articular cartilage defect model was constructed to identify the effect of amniotic membrane/collagen scaffolds on cartilage repair. Cartilage formation was analyzed by imaging and toluene blue staining. Knee joint recovery in rabbits was examined using hematoxylin and eosin, toluidine, safranine, and immunohistochemistry at 12 weeks post-operation. Gene expression was examined using ELISA, RT-PCR, Western blotting, and immunofluorescence. Results: The adipose tissue was effectively differentiated into ADSCs, which further differentiated into chondrogenic, osteogenic, and lipogenic lineages after 3 weeks’ culture in vitro. Compared with platelet-rich plasmon (PRP) scaffolds, the amniotic membrane scaffolds better promoted the growth and differentiation of ADSCs. Additionally, scaffolds containing the PRP and amniotic membrane efficiently enhanced the osteogenic differentiation of ADSCs. The levels of COL1A1, COL2A1, COL10A1, SOX9, and ACAN in ADSCs + amniotic membrane + PRP group were significantly higher than the other groups both in vitro and in vivo. The Wakitani scores of the ADSC + amniotic membrane + PRP group were lower than that in ADSC + PRP (4.4 ± 0.44**), ADSC + amniotic membrane (2.63 ± 0.38**), and control groups (6.733 ± 0.21) at week 12 post-operation. Osteogenesis in rabbits of the ADSC + amniotic membrane + PRP group was significantly upregulated when compared with other groups. Amniotic membranes significantly promoted the expression of cartilage regeneration-related factors (SOX6, SOX9, RUNX2, NKX3-2, MEF2C, and GATA4). The ADSC + PRP + amniotic membrane group exhibited the highest levels of TGF-β, PDGF, and FGF while exhibiting the lowest level of IL-1β, IL6, and TNF-α in articular cavity. Conclusion: Amniotic membrane/collagen combination-based scaffolds promoted the proliferation and cartilage differentiation of ADSCs, and may provide a new treatment paradigm for patients with cartilage injury.
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Affiliation(s)
- Le Cao
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Orthopedics Research Institute of Zhejiang University, Hangzhou, China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
| | - Yuling Tong
- Department of General Practice, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiao Wang
- Shaoxing Shangyu Hospital of Traditional Chinese medicine, Shaoxing, China
| | - Qiang Zhang
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Orthopedics Research Institute of Zhejiang University, Hangzhou, China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
| | - Yiying Qi
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Orthopedics Research Institute of Zhejiang University, Hangzhou, China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
| | - Chenhe Zhou
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Orthopedics Research Institute of Zhejiang University, Hangzhou, China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
| | - Xinning Yu
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Orthopedics Research Institute of Zhejiang University, Hangzhou, China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
| | - Yongping Wu
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Orthopedics Research Institute of Zhejiang University, Hangzhou, China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
| | - Xudong Miao
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Orthopedics Research Institute of Zhejiang University, Hangzhou, China.,Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
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48
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Rossi SMP, Ivone A, Ghiara M, Jannelli E, Sangaletti R, Perticarini L, Benazzo F. A ligament tensor-guided extramedullary alignment technique for distal femoral cut in total knee replacement: results at a minimum 3 years follow-up. Arch Orthop Trauma Surg 2021; 141:2295-2302. [PMID: 34386837 DOI: 10.1007/s00402-021-04115-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Accepted: 08/05/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND Femoral intramedullary canal referencing is used by most knee arthroplasty systems for distal femoral cut; to avoid the opening of the femoral canal different solutions have been presented such as navigation, patient-specific instruments (PSI) or the use of an extramedullary device. The FuZion® system is a tensor device, created to merge the two main techniques for performing a total knee arthroplasty: the ligament balancing and measured resection techniques. Our idea was to use the tensor as an extramedullary cutting guide for the distal femoral cut, based on a 90° tibial resection. METHODS A total of 110 patients were operated on with this technique. Patients were evaluated with weight-bearing long-standing X-rays, knee a-p and lateral views, validated PROMs (Oxford Knee Score, EQ-5D and EQ-VAS), the Knee Society Scoring System (KSS) and the Forgotten Joint Score (FJS). Minimum follow up was 3 years (range 38-50 months). RESULTS Complete results were available for 104 patients (5 were lost in follow up and 1 died). Significant improvements were registered for all the evaluated scores from pre-op to the final follow up. Pre-op long-standing X-rays showed 21 valgus knees (20%) with a mean HKA of 187.6° (± 3.2°), 70 varus knees (62%) with a mean 172.2° (± 3.7°) HKA and 19 neutrally aligned knees, with a mean HKA of 179.5° (0 ± 2°). The radiographic evaluation at 3 months post-op showed 20 valgus knees (mean HKA 183.7° ± 1.5°), 67 varus knees (mean HKA 176.1° ± 1.8°) and 23 neutrally aligned knees with a mean HKA of 179.3° (0 ± 2°). At final follow up the survival rate was 100% for revision of the implant as the endpoint. With any reoperation as the endpoint Kaplan-Meier survival estimate showed a survival rate of 95.1% at 3 years. CONCLUSIONS This technique for performing a ligament driven alignment in total knee arthroplasty showed encouraging clinical outcomes at mid-term follow up leaving a residual deformity on the coronal plane.
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Affiliation(s)
- Stefano Marco Paolo Rossi
- Sezione di Chirurgia Protesica ad Indirizzo Robotico - Unità di Traumatologia dello sport, U.O Ortopedia e Traumatologia Fondazione Poliambulanza, Via Bissolati 57, 25124, Brescia, Italy.
| | - Alessandro Ivone
- Clinica Ortopedica e Traumatologica, Fondazione IRCCS Policlinico San Matteo, P.le Golgi 19, 27100, Pavia, Italy
| | - Matteo Ghiara
- Clinica Ortopedica e Traumatologica, Fondazione IRCCS Policlinico San Matteo, P.le Golgi 19, 27100, Pavia, Italy
| | - Eugenio Jannelli
- Clinica Ortopedica e Traumatologica, Fondazione IRCCS Policlinico San Matteo, P.le Golgi 19, 27100, Pavia, Italy
| | - Rudy Sangaletti
- Sezione di Chirurgia Protesica ad Indirizzo Robotico - Unità di Traumatologia dello sport, U.O Ortopedia e Traumatologia Fondazione Poliambulanza, Via Bissolati 57, 25124, Brescia, Italy
- Clinica Ortopedica e Traumatologica, Fondazione IRCCS Policlinico San Matteo, P.le Golgi 19, 27100, Pavia, Italy
- Università degli Studi di Pavia, 27100, Pavia, Italy
| | - Loris Perticarini
- Sezione di Chirurgia Protesica ad Indirizzo Robotico - Unità di Traumatologia dello sport, U.O Ortopedia e Traumatologia Fondazione Poliambulanza, Via Bissolati 57, 25124, Brescia, Italy
| | - Francesco Benazzo
- Sezione di Chirurgia Protesica ad Indirizzo Robotico - Unità di Traumatologia dello sport, U.O Ortopedia e Traumatologia Fondazione Poliambulanza, Via Bissolati 57, 25124, Brescia, Italy
- Clinica Ortopedica e Traumatologica, Fondazione IRCCS Policlinico San Matteo, P.le Golgi 19, 27100, Pavia, Italy
- Università degli Studi di Pavia, 27100, Pavia, Italy
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de Sousa BM, Correia CR, Ferreira JAF, Mano JF, Furlani EP, Soares Dos Santos MP, Vieira SI. Capacitive interdigitated system of high osteoinductive/conductive performance for personalized acting-sensing implants. NPJ Regen Med 2021; 6:80. [PMID: 34815414 PMCID: PMC8611088 DOI: 10.1038/s41536-021-00184-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Accepted: 10/19/2021] [Indexed: 11/15/2022] Open
Abstract
Replacement orthopedic surgeries are among the most common surgeries worldwide, but clinically used passive implants cannot prevent failure rates and inherent revision arthroplasties. Optimized non-instrumented implants, resorting to preclinically tested bioactive coatings, improve initial osseointegration but lack long-term personalized actuation on the bone-implant interface. Novel bioelectronic devices comprising biophysical stimulators and sensing systems are thus emerging, aiming for long-term control of peri-implant bone growth through biointerface monitoring. These acting-sensing dual systems require high frequency (HF) operations able to stimulate osteoinduction/osteoconduction, including matrix maturation and mineralization. A sensing-compatible capacitive stimulator of thin interdigitated electrodes and delivering an electrical 60 kHz HF stimulation, 30 min/day, is here shown to promote osteoconduction in pre-osteoblasts and osteoinduction in human adipose-derived mesenchymal stem cells (hASCs). HF stimulation through this capacitive interdigitated system had significant effects on osteoblasts' collagen-I synthesis, matrix, and mineral deposition. A proteomic analysis of microvesicles released from electrically-stimulated osteoblasts revealed regulation of osteodifferentiation and mineralization-related proteins (e.g. Tgfb3, Ttyh3, Itih1, Aldh1a1). Proteomics data are available via ProteomeXchange with the identifier PXD028551. Further, under HF stimulation, hASCs exhibited higher osteogenic commitment and enhanced hydroxyapatite deposition. These promising osteoinductive/conductive capacitive stimulators will integrate novel bioelectronic implants able to monitor the bone-implant interface and deliver personalized stimulation to peri-implant tissues.
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Affiliation(s)
- Bárbara M de Sousa
- Department of Medical Sciences, Institute of Biomedicine (iBiMED), University of Aveiro, 3810-193, Aveiro, Portugal
| | - Clara R Correia
- Department of Chemistry, CICECO - Aveiro Institute of Materials, University of Aveiro, 3810-193, Aveiro, Portugal
| | - Jorge A F Ferreira
- Department of Mechanical Engineering, Centre for Mechanical Technology & Automation (TEMA), University of Aveiro, 3810-193, Aveiro, Portugal
| | - João F Mano
- Department of Chemistry, CICECO - Aveiro Institute of Materials, University of Aveiro, 3810-193, Aveiro, Portugal
| | - Edward P Furlani
- Department of Chemical and Biological Engineering, Department of Electrical Engineering, University at Buffalo (SUNY), Buffalo, NY, 14260, USA
| | - Marco P Soares Dos Santos
- Department of Mechanical Engineering, Centre for Mechanical Technology & Automation (TEMA), University of Aveiro, 3810-193, Aveiro, Portugal.
- Faculty of Engineering, Associated Laboratory for Energy, Transports and Aeronautics (LAETA), University of Porto, 4200-465, Porto, Portugal.
| | - Sandra I Vieira
- Department of Medical Sciences, Institute of Biomedicine (iBiMED), University of Aveiro, 3810-193, Aveiro, Portugal.
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50
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Yan J, Liu C, Tu C, Zhang R, Tang X, Li H, Wang H, Ma Y, Zhang Y, Wu H, Sheng G. Hydrogel-hydroxyapatite-monomeric collagen type-I scaffold with low-frequency electromagnetic field treatment enhances osteochondral repair in rabbits. Stem Cell Res Ther 2021; 12:572. [PMID: 34774092 PMCID: PMC8590294 DOI: 10.1186/s13287-021-02638-6] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 10/25/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Cartilage damage is a common medical issue in clinical practice. Complete cartilage repair remains a significant challenge owing to the inferior quality of regenerative tissue. Safe and non-invasive magnetic therapy combined with tissue engineering to repair cartilage may be a promising breakthrough. METHODS In this study, a composite scaffold made of Hydroxyapatite-Collagen type-I (HAC) and PLGA-PEG-PLGA thermogel was produced to match the cartilage and subchondral layers in osteochondral defects, respectively. Bone marrow mesenchymal stem cells (BMSC) encapsulated in the thermogel were stimulated by an electromagnetic field (EMF). Effect of EMF on the proliferation and chondrogenic differentiation potential was evaluated in vitro. 4 mm femoral condyle defect was constructed in rabbits. The scaffolds loaded with BMSCs were implanted into the defects with or without EMF treatment. Effects of the combination treatment of the EMF and composite scaffold on rabbit osteochondral defect was detected in vivo. RESULTS In vitro experiments showed that EMF could promote proliferation and chondrogenic differentiation of BMSCs partly by activating the PI3K/AKT/mTOR and Wnt1/LRP6/β-catenin signaling pathway. In vivo results further confirmed that the scaffold with EMF enhances the repair of osteochondral defects in rabbits, and, in particular, cartilage repair. CONCLUSION Hydrogel-Hydroxyapatite-Monomeric Collagen type-I scaffold with low-frequency EMF treatment has the potential to enhance osteochondral repair.
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Affiliation(s)
- Jiyuan Yan
- Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue 1095, Wuhan, 430030, Hubei, People's Republic of China
| | - Chaoxu Liu
- Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue 1095, Wuhan, 430030, Hubei, People's Republic of China
| | - Chang Tu
- Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China
| | - Ruizhuo Zhang
- Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue 1095, Wuhan, 430030, Hubei, People's Republic of China
| | - Xiangyu Tang
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - Hao Li
- Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue 1095, Wuhan, 430030, Hubei, People's Republic of China
| | - Huaixi Wang
- Department of Spine and Spinal Cord Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Henan, Zhengzhou, People's Republic of China
| | - Yongzhuang Ma
- Department of Orthopedics, Shanxi Bethune Hospital, Taiyuan, Shanxi, People's Republic of China
| | - Yingchi Zhang
- Department of Traumatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue 1095, Wuhan, 430030, Hubei, People's Republic of China.
| | - Hua Wu
- Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue 1095, Wuhan, 430030, Hubei, People's Republic of China.
| | - Gaohong Sheng
- Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue 1095, Wuhan, 430030, Hubei, People's Republic of China.
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