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Chia CSM, Fu SC, He X, Cheng YY, Franco-Obregón A, Hua Y, Yung PSH, Ling SKK. The clinical effects of pulsed electromagnetic field therapy for the management of chronic ankle instability: a study protocol for a double-blind randomized controlled trial. Trials 2024; 25:808. [PMID: 39627831 PMCID: PMC11613907 DOI: 10.1186/s13063-024-08639-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 11/12/2024] [Indexed: 12/08/2024] Open
Abstract
BACKGROUND Chronic ankle instability is associated with long-term neuromuscular deficits involving poor postural control and peroneal muscular impairment. Symptoms of chronic ankle instability hinder engagement in physical activity and undermine the patient's quality of life. Despite the existence of various treatment modalities, none has conclusively provided evidence of clinical effectiveness in counteracting neuromuscular deficits, such as arthrogenic muscle inhibition of the peroneal longus (PL). Pulse electromagnetic field therapy employed as an adjunct biophysical therapy can potentially improve stability by mitigating peroneal muscle weakness and by activating the peroneal muscle. We postulate that by combining standard care (muscle strengthening, balance training, and range of motion exercise) with pulse electromagnetic field therapy, postural control stability and peroneal muscle weakness will significantly improve. METHODS This is a prospective, randomized, double-blind, placebo-controlled trial. A total of 48 adults with chronic ankle instability will be recruited and randomly allocated into either the intervention or control groups. The intervention group (n = 24) will receive active pulse electromagnetic field therapy and standard exercise training, while the control group (n = 24) will receive sham pulse electromagnetic field therapy and standard exercise training for 8 weeks. Primary and secondary outcomes will be evaluated at baseline, week 4, 8 as well as at 3-, 6-, and 12-month follow-up visits. DISCUSSION Chronic ankle instability is a common debilitating condition without a curative conservative treatment. Investigating different treatment modalities will be essential for improving rehabilitation outcomes in this clinical population. This study will investigate the effectiveness of pulsed electromagnetic field therapy on the functional and clinical outcomes in the chronic ankle instability population. This trial may demonstrate this non-invasive biophysical therapy to be an effective measure to help patients with CAI. TRIAL REGISTRATION ClinicalTrials.gov NCT05500885. Registered on August 13, 2022.
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Affiliation(s)
- Cheryl Shu Ming Chia
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong (CUHK), Sha Tin, Hong Kong, China
| | - Sai-Chuen Fu
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong (CUHK), Sha Tin, Hong Kong, China
| | - Xin He
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong (CUHK), Sha Tin, Hong Kong, China
| | - Yang Yang Cheng
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China
| | - Alfredo Franco-Obregón
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore
- Institute of Health Technology and Innovation (iHealthtech), National University of Singapore, Singapore, 117599, Singapore
- Biolonic Currents Electromagnetic Pulsing Systems Laboratory (BICEPS), National University of Singapore, Singapore, 117599, Singapore
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117593, Singapore
- Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore
- Nanomedicine Translational Research Programme, Centre for NanoMedicine, Yong Loo Lin, School of Medicine, National University of Singapore, Singapore, Singapore
- NUS Centre for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599, Singapore
| | - Yinghui Hua
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Patrick Shu-Hang Yung
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong (CUHK), Sha Tin, Hong Kong, China
| | - Samuel Ka-Kin Ling
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong (CUHK), Sha Tin, Hong Kong, China.
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Chen ZY, Wang MH, Ye Z. Effect of electroacupuncture combined with rehabilitation techniques on shoulder function in patients with rotator cuff injuries. World J Clin Cases 2024; 12:4582-4589. [PMID: 39070812 PMCID: PMC11235512 DOI: 10.12998/wjcc.v12.i21.4582] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Revised: 05/27/2024] [Accepted: 06/11/2024] [Indexed: 06/30/2024] Open
Abstract
BACKGROUND The rotator cuff is located below the acromion and deltoid muscles and comprises multiple tendons that wrap around the humeral head, maintaining shoulder joint stability. AIM To explore the effect of electroacupuncture combined with rehabilitation techniques on shoulder function in patients with rotator cuff injuries. METHODS We selected 97 patients with rotator cuff injuries treated in the People's Hospital of Yuhuan from February 2020 to May 2023. Patients were grouped using the envelope method. RESULTS After treatment, the study group's treatment effective rate was 94.90% (46/49 patients), significantly higher than that in the control group (79.17%, 38/48 cases; P < 0.05). Before treatment, there was no difference in Constant Murley Score (CMS) scores, shoulder mobility, or 36-Item Short Form Health Survey (SF-36) scale scores (P > 0.05). Compared with those before treatment, the CMS scores (including pain, daily living ability, shoulder mobility, and muscle strength), all aspects of shoulder mobility (forward flexion, posterior extension, external rotation, internal rotation), and SF-36 scale scores (including physiological, psychological, emotional, physical, vitality, and health status) were higher in both groups after treatment and significantly higher in the study group (P < 0.05). There was no difference in the occurrence of complications between the two treatment groups (P > 0.05). CONCLUSION Electroacupuncture combined with rehabilitation techniques has a good treatment effect on patients with rotator cuff injuries, helps accelerate the recovery of shoulder function, improves the quality of life, and is highly safe.
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Affiliation(s)
- Zhi-Ying Chen
- Department of Rehabilitation, The People's Hospital of Yuhuan, Yuhuan 317600, Zhejiang Province, China
| | - Meng-Hua Wang
- Department of Rehabilitation, The People's Hospital of Yuhuan, Yuhuan 317600, Zhejiang Province, China
| | - Zhong Ye
- Department of Rehabilitation Medicine, Yuhuan Hospital of Traditional Chinese Medicine, Yuhuan 317600, Zhejiang Province, China
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Su DB, Zhao ZX, Yin DC, Ye YJ. Promising application of pulsed electromagnetic fields on tissue repair and regeneration. PROGRESS IN BIOPHYSICS AND MOLECULAR BIOLOGY 2024; 187:36-50. [PMID: 38280492 DOI: 10.1016/j.pbiomolbio.2024.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 12/14/2023] [Accepted: 01/19/2024] [Indexed: 01/29/2024]
Abstract
Tissue repair and regeneration is a vital biological process in organisms, which is influenced by various internal mechanisms and microenvironments. Pulsed electromagnetic fields (PEMFs) are becoming a potential medical technology due to its advantages of effectiveness and non-invasiveness. Numerous studies have demonstrated that PEMFs can stimulate stem cell proliferation and differentiation, regulate inflammatory reactions, accelerate wound healing, which is of great significance for tissue regeneration and repair, providing a solid basis for enlarging its clinical application. However, some important issues such as optimal parameter system and potential deep mechanisms remain to be resolved due to PEMFs window effect and biological complexity. Thus, it is of great importance to comprehensively summarizing and analyzing the literature related to the biological effects of PEMFs in tissue regeneration and repair. This review expounded the biological effects of PEMFs on stem cells, inflammation response, wound healing and musculoskeletal disorders in order to improve the application value of PEMFs in medicine. It is believed that with the continuous exploration of biological effects of PEMFs, it will be applied increasingly widely to tissue repair and other diseases.
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Affiliation(s)
- Dan-Bo Su
- Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, China
| | - Zi-Xu Zhao
- Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, China
| | - Da-Chuan Yin
- Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, China
| | - Ya-Jing Ye
- Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, China.
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Xiao H, Wen B, Yan D, Li Q, Yang Y, Yin X, Chen D, Liu J. Hot spots and frontiers in bone-tendon interface research: a bibliometric analysis and visualization from 2000 to 2023. Front Surg 2024; 10:1326564. [PMID: 38327873 PMCID: PMC10847327 DOI: 10.3389/fsurg.2023.1326564] [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: 10/23/2023] [Accepted: 12/19/2023] [Indexed: 02/09/2024] Open
Abstract
Objective In this research, we investigated the current status, hotspots, frontiers, and trends of research in the field of bone-tendon interface (BTI) from 2000 to 2023, based on bibliometrics and visualization and analysis in CiteSpace, VOSviewer, and a bibliometric package in R software. Methods We collected and organized the papers in the Web of Science core collection (WoSCC) for the past 23 years (2000-2023), and extracted and analyzed the papers related to BTI. The extracted papers were bibliometrically analyzed using CiteSpace for overall publication trends, authors, countries/regions, journals, keywords, research hotspots, and frontiers. Results A total of 1,995 papers met the inclusion criteria. The number of papers published and the number of citations in the field of BTI have continued to grow steadily over the past 23 years. In terms of research contribution, the United States leads in terms of the number and quality of publications, number of citations, and collaborations with other countries, while the United Kingdom and the Netherlands lead in terms of the average number of citations. The University of Leeds publishes the largest number of papers, and among the institutions hosting the 100 most cited papers Hospital for Special Surgery takes the top spot. MCGONAGLE D has published the highest number of papers (73) in the last 10 years. The top three clusters include #0 "psoriatic arthritis", #1 "rotator cuff repair", and #2 "tissue engineering". The structure and function of the BTI and its key mechanisms in the healing process are the key to research, while new therapies such as mechanical stimulation, platelet-rich plasma, mesenchymal stem cells, and biological scaffolds are hot topics and trends in research. Conclusion Over the past 23 years, global research on the BTI has expanded in both breadth and depth. The focus of research has shifted from studies concentrating on the structure of the BTI and the disease itself to new therapies such as biomaterial-based alternative treatments, mechanical stimulation, platelet-rich plasma, etc.
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Affiliation(s)
- Hao Xiao
- XiangYa School of Medicine, Central South University, Changsha, China
| | - Boyuan Wen
- XiangYa School of Medicine, Central South University, Changsha, China
| | - Dong Yan
- XiangYa School of Medicine, Central South University, Changsha, China
| | - Quansi Li
- XiangYa School of Medicine, Central South University, Changsha, China
| | - Yujie Yang
- XiangYa School of Medicine, Central South University, Changsha, China
| | - Xianye Yin
- XiangYa School of Medicine, Central South University, Changsha, China
| | - Deyu Chen
- School of Journalism and Communication, Hunan University, Changsha, China
| | - Jiachen Liu
- XiangYa School of Medicine, Central South University, Changsha, China
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Center of System Biology and Data Information, School of Basic Medical Science, Central South University, Changsha, Hunan, China
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Krupp R, Frankle M, Nyland J, Baker CE, Werner BC, Pierre PS, Tashjian R. Interpositional scaffold anchor rotator cuff footprint tear repair: excellent survival, healing, and early outcomes. Knee Surg Sports Traumatol Arthrosc 2023:10.1007/s00167-023-07383-2. [PMID: 36976315 DOI: 10.1007/s00167-023-07383-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 03/01/2023] [Indexed: 03/29/2023]
Abstract
PURPOSE Shoulder function limitation duration after a full-thickness rotator cuff tendon (RCT) tear may influence post-repair healing and outcomes. A suture anchor was developed to improve footprint repair fixation and healing through biological fluid delivery and scaffold augmentation. The primary multicenter study objective was to evaluate RCT repair failure rate based on 6-month MRI examination, and device survival at 1-year follow-up. The secondary objective was to compare the clinical outcomes of subjects with shorter- and longer-term shoulder function limitation duration. METHODS Seventy-one subjects (46 men) with moderate-to-large RCT tears (1.5-4 cm), at a median 61 years of age (range = 40-76), participated in this study. Pre-repair RCT tear location/size and 6-month healing status were confirmed by an independent radiologist. Subjects with shorter- (Group 1: 17.8 ± 21 days, n = 37) and longer-term (Group 2: 185.4 ± 89 days, n = 34) shoulder function limitation durations were also compared over 1 year for active mobility, strength, American Shoulder and Elbow Surgeon's Shoulder Score (ASES score), Veterans RAND 12 Item Health Survey (VR-12), and visual analog scale (VAS) pain and instability scores. RESULTS Three of the 52 subjects [5.8%] who underwent 6-month MRI experienced a re-tear at the original RCT footprint repair site. By the 1-year follow-up, overall anchor survival was 97%. Although Group 2 displayed lower ASES and VR-12 scores pre-repair (ASES = 40.1 ± 17 vs. 47.9 ± 17; VR-12 physical health (PH) = 37.2 ± 9 vs. 41.4 ± 8) (p ≤ 0.048), at 3-month post-RCT repair (ASES = 61.3 ± 19 vs. 71.3 ± 20; VR-12 PH = 40.8 ± 8 vs. 46.8 ± 9) (p ≤ 0.038), and at 6-month post-RCT repair (ASES = 77.4 ± 18 vs. 87.8 ± 13; VR-12 PH = 48.9 ± 11 vs. 54.0 ± 9) (p ≤ 0.045), by 1-year post-RCT repair, groups did not differ (n.s.). Between-groups VR-12 mental health score differences were not evident at any time period (n.s.). Shoulder pain and instability VAS scores also did not differ (n.s.), displaying comparable improvement between groups from pre-RCT repair to 1-year post-RCT repair. Groups had comparable active shoulder mobility and strength recovery at each follow-up (n.s.). CONCLUSION At 6-month post-RCT repair, only 3/52 of patients [5.8%] had a footprint re-tear, and at 1-year follow-up, overall anchor survival was 97%. Use of this scaffold anchor was associated with excellent early clinical outcomes regardless of shoulder function impairment duration. LEVEL OF EVIDENCE II.
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Affiliation(s)
- Ryan Krupp
- Norton Orthopedic Institute, 9880 Angies Way Suite 250, Louisville, KY, 40241, USA
| | - Mark Frankle
- Florida Orthopaedic Institute, Temple Terrace, USA
| | - John Nyland
- Norton Orthopedic Institute, 9880 Angies Way Suite 250, Louisville, KY, 40241, USA.
- Department of Orthopaedic Surgery, University of Louisville, Louisville, USA.
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Abed T, Ganser K, Eckert F, Stransky N, Huber SM. Ion channels as molecular targets of glioblastoma electrotherapy. Front Cell Neurosci 2023; 17:1133984. [PMID: 37006466 PMCID: PMC10064067 DOI: 10.3389/fncel.2023.1133984] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Accepted: 02/10/2023] [Indexed: 03/19/2023] Open
Abstract
Therapies with weak, non-ionizing electromagnetic fields comprise FDA-approved treatments such as Tumor Treating Fields (TTFields) that are used for adjuvant therapy of glioblastoma. In vitro data and animal models suggest a variety of biological TTFields effects. In particular, effects ranging from direct tumoricidal, radio- or chemotherapy-sensitizing, metastatic spread-inhibiting, up to immunostimulation have been described. Diverse underlying molecular mechanisms, such as dielectrophoresis of cellular compounds during cytokinesis, disturbing the formation of the spindle apparatus during mitosis, and perforating the plasma membrane have been proposed. Little attention, however, has been paid to molecular structures that are predestinated to percept electromagnetic fields-the voltage sensors of voltage-gated ion channels. The present review article briefly summarizes the mode of action of voltage sensing by ion channels. Moreover, it introduces into the perception of ultra-weak electric fields by specific organs of fishes with voltage-gated ion channels as key functional units therein. Finally, this article provides an overview of the published data on modulation of ion channel function by diverse external electromagnetic field protocols. Combined, these data strongly point to a function of voltage-gated ion channels as transducers between electricity and biology and, hence, to voltage-gated ion channels as primary targets of electrotherapy.
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Affiliation(s)
- Tayeb Abed
- Department of Radiation Oncology, University of Tübingen, Tübingen, Germany
| | - Katrin Ganser
- Department of Radiation Oncology, University of Tübingen, Tübingen, Germany
| | - Franziska Eckert
- Department of Radiation Oncology, University of Tübingen, Tübingen, Germany
- Department of Radiation Oncology, Medical University Vienna, Vienna, Austria
| | - Nicolai Stransky
- Department of Radiation Oncology, University of Tübingen, Tübingen, Germany
- Department of Pharmacology, Toxicology and Clinical Pharmacy, Institute of Pharmacy, University of Tübingen, Tübingen, Germany
| | - Stephan M. Huber
- Department of Radiation Oncology, University of Tübingen, Tübingen, Germany
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Homo sapiens—A Species Not Designed for Space Flight: Health Risks in Low Earth Orbit and Beyond, Including Potential Risks When Traveling beyond the Geomagnetic Field of Earth. Life (Basel) 2023; 13:life13030757. [PMID: 36983912 PMCID: PMC10051707 DOI: 10.3390/life13030757] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Revised: 03/03/2023] [Accepted: 03/08/2023] [Indexed: 03/18/2023] Open
Abstract
Homo sapiens and their predecessors evolved in the context of the boundary conditions of Earth, including a 1 g gravity and a geomagnetic field (GMF). These variables, plus others, led to complex organisms that evolved under a defined set of conditions and define how humans will respond to space flight, a circumstance that could not have been anticipated by evolution. Over the past ~60 years, space flight and living in low Earth orbit (LEO) have revealed that astronauts are impacted to varying degrees by such new environments. In addition, it has been noted that astronauts are quite heterogeneous in their response patterns, indicating that such variation is either silent if one remained on Earth, or the heterogeneity unknowingly contributes to disease development during aging or in response to insults. With the planned mission to deep space, humans will now be exposed to further risks from radiation when traveling beyond the influence of the GMF, as well as other potential risks that are associated with the actual loss of the GMF on the astronauts, their microbiomes, and growing food sources. Experimental studies with model systems have revealed that hypogravity conditions can influence a variety biological and physiological systems, and thus the loss of the GMF may have unanticipated consequences to astronauts’ systems, such as those that are electrical in nature (i.e., the cardiovascular system and central neural systems). As astronauts have been shown to be heterogeneous in their responses to LEO, they may require personalized countermeasures, while others may not be good candidates for deep-space missions if effective countermeasures cannot be developed for long-duration missions. This review will discuss several of the physiological and neural systems that are affected and how the emerging variables may influence astronaut health and functioning.
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Yang C, Teng Y, Geng B, Xiao H, Chen C, Chen R, Yang F, Xia Y. Strategies for promoting tendon-bone healing: Current status and prospects. Front Bioeng Biotechnol 2023; 11:1118468. [PMID: 36777256 PMCID: PMC9911882 DOI: 10.3389/fbioe.2023.1118468] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Accepted: 01/06/2023] [Indexed: 01/28/2023] Open
Abstract
Tendon-bone insertion (TBI) injuries are common, primarily involving the rotator cuff (RC) and anterior cruciate ligament (ACL). At present, repair surgery and reconstructive surgery are the main treatments, and the main factor determining the curative effect of surgery is postoperative tendon-bone healing, which requires the stable combination of the transplanted tendon and the bone tunnel to ensure the stability of the joint. Fibrocartilage and bone formation are the main physiological processes in the bone marrow tract. Therefore, therapeutic measures conducive to these processes are likely to be applied clinically to promote tendon-bone healing. In recent years, biomaterials and compounds, stem cells, cell factors, platelet-rich plasma, exosomes, physical therapy, and other technologies have been widely used in the study of promoting tendon-bone healing. This review provides a comprehensive summary of strategies used to promote tendon-bone healing and analyses relevant preclinical and clinical studies. The potential application value of these strategies in promoting tendon-bone healing was also discussed.
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Affiliation(s)
- Chenhui Yang
- Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, China,Orthopaedics Key Laboratory of Gansu Province, Lanzhou University Second Hospital, Lanzhou, China,The Second School of Clinical Medical, Lanzhou University, Lanzhou, China,Department of Orthopedic, Tianshui Hand and Foot Surgery Hospital, Tianshui, China
| | - Yuanjun Teng
- Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, China,Orthopaedics Key Laboratory of Gansu Province, Lanzhou University Second Hospital, Lanzhou, China,The Second School of Clinical Medical, Lanzhou University, Lanzhou, China
| | - Bin Geng
- Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, China,Orthopaedics Key Laboratory of Gansu Province, Lanzhou University Second Hospital, Lanzhou, China,The Second School of Clinical Medical, Lanzhou University, Lanzhou, China
| | - Hefang Xiao
- Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, China,Orthopaedics Key Laboratory of Gansu Province, Lanzhou University Second Hospital, Lanzhou, China,The Second School of Clinical Medical, Lanzhou University, Lanzhou, China
| | - Changshun Chen
- Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, China,Orthopaedics Key Laboratory of Gansu Province, Lanzhou University Second Hospital, Lanzhou, China,The Second School of Clinical Medical, Lanzhou University, Lanzhou, China
| | - Rongjin Chen
- Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, China,Orthopaedics Key Laboratory of Gansu Province, Lanzhou University Second Hospital, Lanzhou, China,The Second School of Clinical Medical, Lanzhou University, Lanzhou, China
| | - Fei Yang
- Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, China,Orthopaedics Key Laboratory of Gansu Province, Lanzhou University Second Hospital, Lanzhou, China,The Second School of Clinical Medical, Lanzhou University, Lanzhou, China
| | - Yayi Xia
- Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, China,Orthopaedics Key Laboratory of Gansu Province, Lanzhou University Second Hospital, Lanzhou, China,The Second School of Clinical Medical, Lanzhou University, Lanzhou, China,*Correspondence: Yayi Xia,
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Hart DA, Ahmed AS, Ackermann P. Optimizing repair of tendon ruptures and chronic tendinopathies: Integrating the use of biomarkers with biological interventions to improve patient outcomes and clinical trial design. Front Sports Act Living 2023; 4:1081129. [PMID: 36685063 PMCID: PMC9853460 DOI: 10.3389/fspor.2022.1081129] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Accepted: 12/09/2022] [Indexed: 01/09/2023] Open
Abstract
Tendons are dense connective tissues of the musculoskeletal system that link bones with muscles to foster mobility. They have complex structures and exist in varying biomechanical, metabolic and biological environments. In addition, tendon composition and mechanical properties can change over the lifespan as an individual ages. Many tendons function in high stress conditions with a low vascular and neuronal supply, conditions often leading to development of chronic tendinopathies, and in some cases, overt rupture of the tissues. Given their essential nature for human mobility and navigation through the environment, the effective repair and regeneration of different tendons after injury or damage is critical for quality of life, and for elite athletes, the return to sport participation at a high level. However, for mainly unknown reasons, the outcomes following injury are not always successful and lead to functional compromise and risk for re-injury. Thus, there is a need to identify those patients who are at risk for developing tendon problems, as well those at risk for poor outcomes after injury and to design interventions to improve outcomes after injury or rupture to specific tendons. This review will discuss recent advances in the identification of biomarkers prognostic for successful and less successful outcomes after tendon injury, and the mechanistic implications of such biomarkers, as well as the potential for specific biologic interventions to enhance outcomes to improve both quality of life and a return to participation in sports. In addition, the implication of these biomarkers for clinical trial design is discussed, as is the issue of whether such biomarkers for successful healing of one tendon can be extended to all tendons or are valid only for tendons in specific biomechanical and biological environments. As maintaining an active lifestyle is critical for health, the successful implementation of these advances will benefit the large number of individuals at risk.
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Affiliation(s)
- David A. Hart
- Department of Surgery, Faculty of Kinesiology, McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB, Canada,Correspondence: David A. Hart
| | - Aisha S. Ahmed
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - Paul Ackermann
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
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Luo W, Wang Y, Han Q, Wang Z, Jiao J, Gong X, Liu Y, Zhang A, Zhang H, Chen H, Wang J, Wu M. Advanced strategies for constructing interfacial tissues of bone and tendon/ligament. J Tissue Eng 2022; 13:20417314221144714. [PMID: 36582940 PMCID: PMC9793068 DOI: 10.1177/20417314221144714] [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: 07/28/2022] [Accepted: 11/26/2022] [Indexed: 12/25/2022] Open
Abstract
Enthesis, the interfacial tissue between a tendon/ligament and bone, exhibits a complex histological transition from soft to hard tissue, which significantly complicates its repair and regeneration after injury. Because traditional surgical treatments for enthesis injury are not satisfactory, tissue engineering has emerged as a strategy for improving treatment success. Rapid advances in enthesis tissue engineering have led to the development of several strategies for promoting enthesis tissue regeneration, including biological scaffolds, cells, growth factors, and biophysical modulation. In this review, we discuss recent advances in enthesis tissue engineering, particularly the use of biological scaffolds, as well as perspectives on the future directions in enthesis tissue engineering.
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Affiliation(s)
- Wangwang Luo
- Department of Orthopedics, The Second
Hospital of Jilin University, Changchun, China
| | - Yang Wang
- Department of Orthopedics, The Second
Hospital of Jilin University, Changchun, China
| | - Qing Han
- Department of Orthopedics, The Second
Hospital of Jilin University, Changchun, China
| | - Zhonghan Wang
- Department of Orthopedics, The Second
Hospital of Jilin University, Changchun, China,Orthopaedic Research Institute of Jilin
Province, Changchun, China
| | - Jianhang Jiao
- Department of Orthopedics, The Second
Hospital of Jilin University, Changchun, China
| | - Xuqiang Gong
- Department of Orthopedics, The Second
Hospital of Jilin University, Changchun, China
| | - Yang Liu
- Department of Orthopedics, The Second
Hospital of Jilin University, Changchun, China
| | - Aobo Zhang
- Department of Orthopedics, The Second
Hospital of Jilin University, Changchun, China
| | - Han Zhang
- Department of Orthopedics, The Second
Hospital of Jilin University, Changchun, China
| | - Hao Chen
- Department of Orthopedics, The Second
Hospital of Jilin University, Changchun, China
| | - Jincheng Wang
- Department of Orthopedics, The Second
Hospital of Jilin University, Changchun, China
| | - Minfei Wu
- Department of Orthopedics, The Second
Hospital of Jilin University, Changchun, China,Minfei Wu, Department of Orthopedics, The
Second Hospital of Jilin University, 218 Ziqiang Sreet, Changchun 130041, China.
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Wang M, Li Y, Feng L, Zhang X, Wang H, Zhang N, Viohl I, Li G. Pulsed Electromagnetic Field Enhances Healing of a Meniscal Tear and Mitigates Posttraumatic Osteoarthritis in a Rat Model. Am J Sports Med 2022; 50:2722-2732. [PMID: 35834942 DOI: 10.1177/03635465221105874] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Meniscal tears in the avascular region are thought to rarely heal and are a considerable challenge to treat. Although the therapeutic effects of a pulsed electromagnetic field (PEMF) have been extensively studied in a variety of orthopaedic disorders, the effect of a PEMF on meniscal healing has not been reported. HYPOTHESIS PEMF treatment would promote meniscal healing and prevent osteoarthritis progression. STUDY DESIGN Controlled laboratory study. METHODS A total of 72 twelve-week-old male Sprague-Dawley rats with full-thickness longitudinal medial meniscal tears in the avascular region were divided into 3 groups: control (Gcon), treatment with a classic signal PEMF (Gclassic), and treatment with a high-slew rate signal PEMF (GHSR). Macroscopic observation and histological analysis of the meniscus and articular cartilage were performed to evaluate the meniscal healing and progression of osteoarthritis. The synovium was harvested for histological and immunofluorescent analysis to evaluate the intra-articular inflammation. Meniscal healing, articular cartilage degeneration, and synovitis were quantitatively evaluated according to their scoring systems. RESULTS Dramatic degenerative changes of the meniscus and articular cartilage were noticed during gross observation and histological evaluation in Gcon at 8 weeks. However, the menisci in the 2 treatment groups were restored to normal morphology, with a smooth surface and shiny white color. Particularly, the HSR signal remarkably enhanced the fibrochondrogenesis and accelerated the remodeling process of the regenerated tissue. The meniscal healing scores of the PEMF treatment groups were significantly higher than those in Gcon at 8 weeks. Specifically, the HSR signal showed a significantly higher meniscal repair score than did the classic signal at week 8 (P < .01). Additionally, the HSR signal significantly downregulated the secretion levels of interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) in the meniscus and synovium as compared with the control group. When compared with the 2 treatment groups, Gcon had significantly higher degeneration scores (Gcon vs Gclassic, P < .0001; Gcon vs GHSR, P < .0001). The HSR signal also exhibited significantly lower synovitis scores compared with the other two groups (Gcon vs Gclassic, P < .0001; Gclassic vs GHSR, P = .0002). CONCLUSION A PEMF promoted the healing of meniscal tears in the avascular region and restored the injured meniscus to its structural integrity in a rat model. As compared with the classic signal, the HSR signal showed increased capability to promote fibrocartilaginous tissue formation and modulate the inflammatory environment, therefore protecting the knee joint from posttraumatic osteoarthritis development. CLINICAL RELEVANCE Adjuvant PEMF therapy may offer a new approach for the treatment of meniscal tears attributed to the enhanced meniscal repair and ameliorated osteoarthritis progression.
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Affiliation(s)
- Ming Wang
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Yucong Li
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Lu Feng
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Xiaoting Zhang
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Haixing Wang
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - Nianli Zhang
- Research and Clinical Affairs, Orthofix Medical Inc, Lewisville, Texas, USA
| | - Ingmar Viohl
- Research and Clinical Affairs, Orthofix Medical Inc, Lewisville, Texas, USA
| | - Gang Li
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
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Chen MY, Li J, Zhang N, Waldorff EI, Ryaby JT, Fedor P, Jia Y, Wang Y. In Vitro and in Vivo Study of the Effect of Osteogenic Pulsed Electromagnetic Fields on Breast and Lung Cancer Cells. Technol Cancer Res Treat 2022; 21:15330338221124658. [PMID: 36172744 PMCID: PMC9523832 DOI: 10.1177/15330338221124658] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Introduction: Although there have been significant advances in research and treatments over the past decades, cancer remains a leading cause of morbidity and mortality, mostly due to resistance to standard therapies. Pulsed electromagnetic field (PEMF), a newly emerged therapeutic strategy, has been highly regarded as less invasive and almost safe to patients, is now a clinically accepted form to treat diseases including cancer. Breast and lung cancer are the most prevalent forms of human cancers, yet reported investigations on exploring regimes including PEMF are limited. Methods: Intended to examine the anti-tumor effects of a clinically accepted osteogenic PEMF and the possibility of including PEMF in breast and lung cancer treatments, we studied the effects of 2 PEMF signals (PMF1 and PMF2) on breast and lung cancer cell growth and proliferation, as well as the possible underline mechanisms in vitro and in vivo. Results: We found that both signals caused modest but significant growth inhibition (∼5%) in MCF-7 and A549 cancer cells. Interestingly, mice xenograft tumors with A549 cells treated by PEMF were smaller in sizes than controls. However, for mice with MCF-7 tumor implants, treatment with PMF1 resulted in a slight increase (2.8%) in mean tumor size, while PMF2 treated tumors showed a 9% reduction in average size. Furthermore, PEMF increased caspase 3/7 expression levels and percentage of annexin stained cells, indicating the induction of apoptosis. It also increased G0 by 8.5%, caused changes in the expression of genes associated with cell growth suppression, DNA damage, cell cycle arrest, and apoptosis. When cancer cells or xenograft tumors treated with combined PEMF and chemotherapy drugs, PEMF showed growth inhibition effect independent of cisplatin in A549 cells, but with added effect by pemetrexed for the inhibition of MCF-7 growth. Conclusion: Together, our data suggested that clinically used osteogenic PEMF signals moderately suppressed cancer cell growth and proliferation both in vitro and in vivo.
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Affiliation(s)
- Mike Y Chen
- Division of Neurosurgery, 20220City of Hope National Medical Center, Duarte, CA, USA
| | - Jing Li
- Division of Neurosurgery, 20220City of Hope National Medical Center, Duarte, CA, USA
| | | | | | | | - Philip Fedor
- Division of Neurosurgery, 20220City of Hope National Medical Center, Duarte, CA, USA
| | - Yongsheng Jia
- Division of Neurosurgery, 20220City of Hope National Medical Center, Duarte, CA, USA
| | - Yujun Wang
- Division of Neurosurgery, 20220City of Hope National Medical Center, Duarte, CA, USA
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