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Sawyer M, Semodji A, Nielson O, Rektor A, Burgoyne H, Eppel M, Eixenberger J, Montenegro-Brown R, Nelson ML, Lujan T, Estrada D. Direct Scaffold-Coupled Electrical Stimulation of Chondrogenic Progenitor Cells through Graphene Foam Bioscaffolds to Control Mechanical Properties of Graphene Foam - Cell Composites. RESEARCH SQUARE 2024:rs.3.rs-5589589. [PMID: 39764126 PMCID: PMC11703340 DOI: 10.21203/rs.3.rs-5589589/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/12/2025]
Abstract
Osteoarthritis, a major global cause of pain and disability, is driven by the irreversible degradation of hyaline cartilage in joints. Cartilage tissue engineering presents a promising therapeutic avenue, but success hinges on replicating the native physiological environment to guide cellular behavior and generate tissue constructs that mimic natural cartilage. Although electrical stimulation has been shown to enhance chondrogenesis and extracellular matrix production in 2D cultures, the mechanisms underlying these effects remain poorly understood, particularly in 3D models. Here, we report that direct scaffold-coupled electrical stimulation applied to 3D graphene foam bioscaffolds significantly enhances the mechanical properties of the resulting graphene foam - cell constructs. Using custom 3D-printed electrical stimulus chambers, we applied biphasic square impulses (20, 40, 60 mVpp at 1 kHz) for 5 minutes daily over 7 days. Stimulation at 60 mVpp increased the steady-state energy dissipation and equilibrium modulus by approximately 65% and 25%, respectively, compared to unstimulated controls, while also yielding the highest cell density among stimulated samples. In addition, our custom chambers facilitated full submersion of the hydrophobic graphene foam in media, leading to enhanced cell attachment and integration across the scaffold surface and within its hollow branches. To assess this cellular integration, we employed co-localized confocal fluorescence microscopy and X-ray microCT imaging enabled by colloidal gold nanoparticle and fluorophore staining, which allowed visualization of cell distribution within the opaque scaffold's internal structure. These findings highlight the potential of direct scaffold-coupled electrical stimulus to modulate the mechanical properties of engineered tissues and offer new insights into the emergent behavior of cells within conductive 3D bioscaffolds.
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Tian JS, Tay A. Progress on Electro-Enhancement of Cell Manufacturing. SMALL METHODS 2024; 8:e2301281. [PMID: 38059759 DOI: 10.1002/smtd.202301281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Revised: 11/09/2023] [Indexed: 12/08/2023]
Abstract
With the long persistence of complex, chronic diseases in society, there is increasing motivation to develop cells as living medicine to treat diseases ranging from cancer to wounds. While cell therapies can significantly impact healthcare, the shortage of starter cells meant that considerable raw materials must be channeled solely for cell expansion, leading to expensive products with long manufacturing time which can prevent accessibility by patients who either cannot afford the treatment or have highly aggressive diseases and cannot wait that long. Over the last three decades, there has been increasing knowledge on the effects of electrical modulation on proliferation, but to the best of the knowledge, none of these studies went beyond how electro-control of cell proliferation may be extended to enhance industrial scale cell manufacturing. Here, this review is started by discussing the importance of maximizing cell yield during manufacturing before comparing strategies spanning biomolecular/chemical/physical to modulate cell proliferation. Next, the authors describe how factors governing invasive and non-invasive electrical stimulation (ES) including capacitive coupling electric field may be modified to boost cell manufacturing. This review concludes by describing what needs to be urgently performed to bridge the gap between academic investigation of ES to industrial applications.
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Affiliation(s)
- Johann Shane Tian
- Department of Biomedical Engineering, National University of Singapore, Singapore, 117583, Singapore
| | - Andy Tay
- Department of Biomedical Engineering, National University of Singapore, Singapore, 117583, Singapore
- Institute for Health Innovation and Technology, National University of Singapore, Singapore, 117599, Singapore
- NUS Tissue Engineering Program, National University of Singapore, Singapore, 117510, Singapore
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3
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Chen L, Yang J, Cai Z, Huang Y, Xiao P, Wang J, Wang F, Huang W, Cui W, Hu N. Electroactive Biomaterials Regulate the Electrophysiological Microenvironment to Promote Bone and Cartilage Tissue Regeneration. ADVANCED FUNCTIONAL MATERIALS 2024; 34. [DOI: 10.1002/adfm.202314079] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Indexed: 01/06/2025]
Abstract
AbstractThe incidence of large bone and articular cartilage defects caused by traumatic injury is increasing worldwide; the tissue regeneration process for these injuries is lengthy due to limited self‐healing ability. Endogenous bioelectrical phenomenon has been well recognized to play an important role in bone and cartilage homeostasis and regeneration. Studies have reported that electrical stimulation (ES) can effectively regulate various biological processes and holds promise as an external intervention to enhance the synthesis of the extracellular matrix, thereby accelerating the process of bone and cartilage regeneration. Hence, electroactive biomaterials have been considered a biomimetic approach to ensure functional recovery by integrating various physiological signals, including electrical, biochemical, and mechanical signals. This review will discuss the role of endogenous bioelectricity in bone and cartilage tissue, as well as the effects of ES on cellular behaviors. Then, recent advances in electroactive materials and their applications in bone and cartilage tissue regeneration are systematically overviewed, with a focus on their advantages and disadvantages as tissue repair materials and performances in the modulation of cell fate. Finally, the significance of mimicking the electrophysiological microenvironment of target tissue is emphasized and future development challenges of electroactive biomaterials for bone and cartilage repair strategies are proposed.
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Affiliation(s)
- Li Chen
- Department of Orthopedics The First Affiliated Hospital of Chongqing Medical University Orthopaedic Research Laboratory, Chongqing Medical University Chongqing 400016 China
| | - Jianye Yang
- Department of Orthopedics The First Affiliated Hospital of Chongqing Medical University Orthopaedic Research Laboratory, Chongqing Medical University Chongqing 400016 China
| | - Zhengwei Cai
- Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine 197 Ruijin 2nd Road Shanghai 200025 P. R. China
| | - Yanran Huang
- Department of Orthopedics The First Affiliated Hospital of Chongqing Medical University Orthopaedic Research Laboratory, Chongqing Medical University Chongqing 400016 China
| | - Pengcheng Xiao
- Department of Orthopedics The First Affiliated Hospital of Chongqing Medical University Orthopaedic Research Laboratory, Chongqing Medical University Chongqing 400016 China
| | - Juan Wang
- Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine 197 Ruijin 2nd Road Shanghai 200025 P. R. China
| | - Fan Wang
- Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine 197 Ruijin 2nd Road Shanghai 200025 P. R. China
| | - Wei Huang
- Department of Orthopedics The First Affiliated Hospital of Chongqing Medical University Orthopaedic Research Laboratory, Chongqing Medical University Chongqing 400016 China
| | - Wenguo Cui
- Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine 197 Ruijin 2nd Road Shanghai 200025 P. R. China
| | - Ning Hu
- Department of Orthopedics The First Affiliated Hospital of Chongqing Medical University Orthopaedic Research Laboratory, Chongqing Medical University Chongqing 400016 China
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4
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Lin JJ, Ning T, Jia SC, Li KJ, Huang YC, Liu Q, Lin JH, Zhang XT. Evaluation of genetic response of mesenchymal stem cells to nanosecond pulsed electric fields by whole transcriptome sequencing. World J Stem Cells 2024; 16:305-323. [PMID: 38577234 PMCID: PMC10989289 DOI: 10.4252/wjsc.v16.i3.305] [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: 12/13/2023] [Revised: 01/31/2024] [Accepted: 02/28/2024] [Indexed: 03/25/2024] Open
Abstract
BACKGROUND Mesenchymal stem cells (MSCs) modulated by various exogenous signals have been applied extensively in regenerative medicine research. Notably, nanosecond pulsed electric fields (nsPEFs), characterized by short duration and high strength, significantly influence cell phenotypes and regulate MSCs differentiation via multiple pathways. Consequently, we used transcriptomics to study changes in messenger RNA (mRNA), long noncoding RNA (lncRNA), microRNA (miRNA), and circular RNA expression during nsPEFs application. AIM To explore gene expression profiles and potential transcriptional regulatory mechanisms in MSCs pretreated with nsPEFs. METHODS The impact of nsPEFs on the MSCs transcriptome was investigated through whole transcriptome sequencing. MSCs were pretreated with 5-pulse nsPEFs (100 ns at 10 kV/cm, 1 Hz), followed by total RNA isolation. Each transcript was normalized by fragments per kilobase per million. Fold change and difference significance were applied to screen the differentially expressed genes (DEGs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to elucidate gene functions, complemented by quantitative polymerase chain reaction verification. RESULTS In total, 263 DEGs were discovered, with 92 upregulated and 171 downregulated. DEGs were predominantly enriched in epithelial cell proliferation, osteoblast differentiation, mesenchymal cell differentiation, nuclear division, and wound healing. Regarding cellular components, DEGs are primarily involved in condensed chromosome, chromosomal region, actin cytoskeleton, and kinetochore. From aspect of molecular functions, DEGs are mainly involved in glycosaminoglycan binding, integrin binding, nuclear steroid receptor activity, cytoskeletal motor activity, and steroid binding. Quantitative real-time polymerase chain reaction confirmed targeted transcript regulation. CONCLUSION Our systematic investigation of the wide-ranging transcriptional pattern modulated by nsPEFs revealed the differential expression of 263 mRNAs, 2 miRNAs, and 65 lncRNAs. Our study demonstrates that nsPEFs may affect stem cells through several signaling pathways, which are involved in vesicular transport, calcium ion transport, cytoskeleton, and cell differentiation.
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Affiliation(s)
- Jian-Jing Lin
- Department of Sports Medicine and Rehabilitation, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, China
| | - Tong Ning
- Institute of Medical Science, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, Shandong Province, China
| | - Shi-Cheng Jia
- Department of Sports Medicine and Rehabilitation, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, China
| | - Ke-Jia Li
- Department of Biomedical Engineering, Institute of Future Technology, Peking University, Beijing 100871, China
| | - Yong-Can Huang
- Shenzhen Engineering Laboratory of Orthopaedic Regenerative Technologies, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, China
| | - Qiang Liu
- Arthritis Clinical and Research Center, Peking University People's Hospital, Beijing 100044, China
| | - Jian-Hao Lin
- Arthritis Clinical and Research Center, Peking University People's Hospital, Beijing 100044, China
| | - Xin-Tao Zhang
- Department of Sports Medicine and Rehabilitation, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, China.
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5
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Ricotti L, Cafarelli A, Manferdini C, Trucco D, Vannozzi L, Gabusi E, Fontana F, Dolzani P, Saleh Y, Lenzi E, Columbaro M, Piazzi M, Bertacchini J, Aliperta A, Cain M, Gemmi M, Parlanti P, Jost C, Fedutik Y, Nessim GD, Telkhozhayeva M, Teblum E, Dumont E, Delbaldo C, Codispoti G, Martini L, Tschon M, Fini M, Lisignoli G. Ultrasound Stimulation of Piezoelectric Nanocomposite Hydrogels Boosts Chondrogenic Differentiation in Vitro, in Both a Normal and Inflammatory Milieu. ACS NANO 2024; 18:2047-2065. [PMID: 38166155 PMCID: PMC10811754 DOI: 10.1021/acsnano.3c08738] [Citation(s) in RCA: 18] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 12/11/2023] [Accepted: 12/14/2023] [Indexed: 01/04/2024]
Abstract
The use of piezoelectric nanomaterials combined with ultrasound stimulation is emerging as a promising approach for wirelessly triggering the regeneration of different tissue types. However, it has never been explored for boosting chondrogenesis. Furthermore, the ultrasound stimulation parameters used are often not adequately controlled. In this study, we show that adipose-tissue-derived mesenchymal stromal cells embedded in a nanocomposite hydrogel containing piezoelectric barium titanate nanoparticles and graphene oxide nanoflakes and stimulated with ultrasound waves with precisely controlled parameters (1 MHz and 250 mW/cm2, for 5 min once every 2 days for 10 days) dramatically boost chondrogenic cell commitment in vitro. Moreover, fibrotic and catabolic factors are strongly down-modulated: proteomic analyses reveal that such stimulation influences biological processes involved in cytoskeleton and extracellular matrix organization, collagen fibril organization, and metabolic processes. The optimal stimulation regimen also has a considerable anti-inflammatory effect and keeps its ability to boost chondrogenesis in vitro, even in an inflammatory milieu. An analytical model to predict the voltage generated by piezoelectric nanoparticles invested by ultrasound waves is proposed, together with a computational tool that takes into consideration nanoparticle clustering within the cell vacuoles and predicts the electric field streamline distribution in the cell cytoplasm. The proposed nanocomposite hydrogel shows good injectability and adhesion to the cartilage tissue ex vivo, as well as excellent biocompatibility in vivo, according to ISO 10993. Future perspectives will involve preclinical testing of this paradigm for cartilage regeneration.
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Affiliation(s)
- Leonardo Ricotti
- The
BioRobotics Institute, Scuola Superiore
Sant’Anna, Piazza Martiri della Libertà 33, 56127 Pisa, Italy
- Department
of Excellence in Robotics & AI, Scuola
Superiore Sant’Anna, Piazza Martiri della Libertà 33, 56127 Pisa, Italy
| | - Andrea Cafarelli
- The
BioRobotics Institute, Scuola Superiore
Sant’Anna, Piazza Martiri della Libertà 33, 56127 Pisa, Italy
- Department
of Excellence in Robotics & AI, Scuola
Superiore Sant’Anna, Piazza Martiri della Libertà 33, 56127 Pisa, Italy
| | - Cristina Manferdini
- Laboratorio
di Immunoreumatologia e Rigenerazione Tissutale, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
| | - Diego Trucco
- The
BioRobotics Institute, Scuola Superiore
Sant’Anna, Piazza Martiri della Libertà 33, 56127 Pisa, Italy
- Department
of Excellence in Robotics & AI, Scuola
Superiore Sant’Anna, Piazza Martiri della Libertà 33, 56127 Pisa, Italy
- Laboratorio
di Immunoreumatologia e Rigenerazione Tissutale, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
| | - Lorenzo Vannozzi
- The
BioRobotics Institute, Scuola Superiore
Sant’Anna, Piazza Martiri della Libertà 33, 56127 Pisa, Italy
- Department
of Excellence in Robotics & AI, Scuola
Superiore Sant’Anna, Piazza Martiri della Libertà 33, 56127 Pisa, Italy
| | - Elena Gabusi
- Laboratorio
di Immunoreumatologia e Rigenerazione Tissutale, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
| | - Francesco Fontana
- The
BioRobotics Institute, Scuola Superiore
Sant’Anna, Piazza Martiri della Libertà 33, 56127 Pisa, Italy
- Department
of Excellence in Robotics & AI, Scuola
Superiore Sant’Anna, Piazza Martiri della Libertà 33, 56127 Pisa, Italy
| | - Paolo Dolzani
- Laboratorio
di Immunoreumatologia e Rigenerazione Tissutale, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
| | - Yasmin Saleh
- Laboratorio
di Immunoreumatologia e Rigenerazione Tissutale, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
| | - Enrico Lenzi
- Laboratorio
di Immunoreumatologia e Rigenerazione Tissutale, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
| | - Marta Columbaro
- Piattaforma
di Microscopia Elettronica, IRCCS Istituto
Ortopedico Rizzoli, 40136 Bologna, Italy
| | - Manuela Piazzi
- Istituto
di Genetica Molecolare “Luigi Luca Cavalli-Sforza”, Consiglio Nazionale delle Ricerche (IGM-CNR), 40136 Bologna, Italy
- IRCCS Istituto
Ortopedico Rizzoli, 40136 Bologna, Italy
| | - Jessika Bertacchini
- Department
of Surgery, Medicine, Dentistry and Morphological Sciences with Interest
in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, 41125 Modena, Italy
| | - Andrea Aliperta
- The
BioRobotics Institute, Scuola Superiore
Sant’Anna, Piazza Martiri della Libertà 33, 56127 Pisa, Italy
- Department
of Excellence in Robotics & AI, Scuola
Superiore Sant’Anna, Piazza Martiri della Libertà 33, 56127 Pisa, Italy
| | - Markys Cain
- Electrosciences
Ltd., Farnham, Surrey GU9 9QT, U.K.
| | - Mauro Gemmi
- Center
for Materials Interfaces, Electron Crystallography, Istituto Italiano di Tecnologia, Viale Rinaldo Piaggio 34, 56025 Pontedera, Italy
| | - Paola Parlanti
- Center
for Materials Interfaces, Electron Crystallography, Istituto Italiano di Tecnologia, Viale Rinaldo Piaggio 34, 56025 Pontedera, Italy
| | - Carsten Jost
- PlasmaChem
GmbH, Schwarzschildstraße
10, 12489 Berlin, Germany
| | - Yirij Fedutik
- PlasmaChem
GmbH, Schwarzschildstraße
10, 12489 Berlin, Germany
| | - Gilbert Daniel Nessim
- Department
of Chemistry and Institute of Nanotechnology, Bar-Ilan University, Ramat
Gan 52900, Israel
| | - Madina Telkhozhayeva
- Department
of Chemistry and Institute of Nanotechnology, Bar-Ilan University, Ramat
Gan 52900, Israel
| | - Eti Teblum
- Department
of Chemistry and Institute of Nanotechnology, Bar-Ilan University, Ramat
Gan 52900, Israel
| | | | - Chiara Delbaldo
- Struttura
Complessa Scienze e Tecnologie Chirurgiche, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy
| | - Giorgia Codispoti
- Struttura
Complessa Scienze e Tecnologie Chirurgiche, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy
| | - Lucia Martini
- Struttura
Complessa Scienze e Tecnologie Chirurgiche, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy
| | - Matilde Tschon
- Struttura
Complessa Scienze e Tecnologie Chirurgiche, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy
| | - Milena Fini
- Scientific Director, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
| | - Gina Lisignoli
- Laboratorio
di Immunoreumatologia e Rigenerazione Tissutale, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
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6
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Suito H, Minamizono W, Yashima N, Matsunaga H, Fujikawa K, Ohsako M. Vector potential dual effect of promoting the proliferation of chondrocytes and inhibiting the calcification process in the articular cartilage. Sci Rep 2023; 13:16845. [PMID: 37803162 PMCID: PMC10558497 DOI: 10.1038/s41598-023-43949-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Accepted: 09/30/2023] [Indexed: 10/08/2023] Open
Abstract
OA commonly affects the articular cartilage of the tibia, and its calcification worsens its advancement and its prevalence has recently increased. Vector potential (VP) represents a novel physical therapy for treating OA. Since the impact of VP on articular cartilage remains unknown, we aimed to assess its effects on articular cartilage and its potential as a new treatment for OA. Here, we divided 24 male Wistar rats, 6-week-old, into control (CO, n = 12) and VP stimulus (n = 12) groups (VP conditions: volt, 67 mV; frequency, 20 kHz; current, 0.12 mA; experimental frequency, 30 min/days, 5 days/week, and 3 weeks). Articular cartilage can be classified into four layers: superficial, medial, deep, and calcified. Moreover, the number of chondrocytes in the articular cartilage was higher in the CO group compared to the VP group, although the calcified layer was thinner in the VP group. Furthermore, MKi67 exhibited higher expression in the VP group than in the CO group, while ectonucleotide pyrophosphatase/phosphodiesterase 1 was downregulated in the VP group. Our findings indicate that VP positively influenced chondrocyte proliferation and inhibited calcification in articular cartilage. Thus, VP stimulation may assist in the development of novel strategies for preventing OA.
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Affiliation(s)
- Hirai Suito
- Graduate School of Human Life Design, Toyo University, 1-7-11 Akabanedai, Kita-Ku, Tokyo, 115-8650, Japan.
- Japan Society for the Promotion of Science Research Fellowships DC, 5-3-1 Koji-Machi, Chiyoda-Ku, Tokyo, 102-0083, Japan.
| | - Wataru Minamizono
- Graduate School of Human Life Design, Toyo University, 1-7-11 Akabanedai, Kita-Ku, Tokyo, 115-8650, Japan
| | - Nao Yashima
- Graduate School of Health Sports Science, Toyo University, 1-7-11 Akabanedai, Kita-Ku, Tokyo, 115-8650, Japan
| | - Hiroya Matsunaga
- Graduate School of Health Sports Science, Toyo University, 1-7-11 Akabanedai, Kita-Ku, Tokyo, 115-8650, Japan
| | - Kaoru Fujikawa
- Department of Oral Anatomy and Developmental Biology, Showa University School of Density, 1-5-8, Hatanodai, Shinagawa-Ku, Tokyo, Japan
| | - Masafumi Ohsako
- Graduate School of Health Sports Science, Toyo University, 1-7-11 Akabanedai, Kita-Ku, Tokyo, 115-8650, Japan
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7
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Wang X, Li X. Regulation of pain neurotransmitters and chondrocytes metabolism mediated by voltage-gated ion channels: A narrative review. Heliyon 2023; 9:e17989. [PMID: 37501995 PMCID: PMC10368852 DOI: 10.1016/j.heliyon.2023.e17989] [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: 01/15/2023] [Revised: 05/15/2023] [Accepted: 07/04/2023] [Indexed: 07/29/2023] Open
Abstract
Osteoarthritis (OA) is one of the leading causes of chronic pain and dysfunction. It is essential to comprehend the nature of pain and cartilage degeneration and its influencing factors on OA treatment. Voltage-gated ion channels (VGICs) are essential in chondrocytes and extracellular matrix (ECM) metabolism and regulate the pain neurotransmitters between the cartilage and the central nervous system. This narrative review focused primarily on the effects of VGICs regulating pain neurotransmitters and chondrocytes metabolism, and most studies have focused on voltage-sensitive calcium channels (VSCCs), voltage-gated sodium channels (VGSCs), acid-sensing ion channels (ASICs), voltage-gated potassium channels (VGKCs), voltage-gated chloride channels (VGCCs). Various ion channels coordinate to maintain the intracellular environment's homeostasis and jointly regulate metabolic and pain under normal circumstances. In the OA model, the ion channel transport of chondrocytes is abnormal, and calcium influx is increased, which leads to increased neuronal excitability. The changes in ion channels are strongly associated with the OA disease process and individual OA risk factors. Future studies should explore how VGICs affect the metabolism of chondrocytes and their surrounding tissues, which will help clinicians and pharmacists to develop more effective targeted drugs to alleviate the progression of OA disease.
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8
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Zhao J, Lu H, Xu D, Sun R, Fang C, Zhao Q, He C, Pan Y, Xu F, Jiang T. Neutrophil membrane-coated nanoparticles for enhanced nanosecond pulsed electric field treatment of pancreatic cancer. Int J Hyperthermia 2022; 39:1026-1035. [PMID: 35914867 DOI: 10.1080/02656736.2022.2093994] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/16/2022] Open
Abstract
OBJECTIVE Pancreatic cancer is one of the leading causes of cancer-related deaths worldwide. Poor prognosis and low survival rates have driven the development of novel therapeutic strategies. Nanosecond pulsed electric field has emerged as a novel, minimal invasive and non-thermal treatment for solid tumors. It is of great significance to study the combination therapy of nsPEF and other treatment strategies for pancreatic cancer. METHODS We developed neutrophil membrane-wrapped liposomal nanoparticles loaded with gemcitabine (NE/Lip-GEM) and investigated their use as a complementary agent for nsPEF treatment. RESULTS Our results showed that neutrophil-mediated delivery of liposomal-gemcitabine (NE/Lip-GEM) efficiently inhibited the growth of pancreatic tumors in mice whose has been treated with incomplete nsPEF ablation. CONCLUSIONS The combination of nsPEF and NE/Lip-GEM may be a promising synergistic strategy for pancreatic cancer therapy.
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Affiliation(s)
- Jing Zhao
- Department of Ultrasound, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.,Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China
| | - Huidan Lu
- Department of Infectious Diseases, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Danxia Xu
- Department of Ultrasound, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Ruiqi Sun
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China
| | - Chengyu Fang
- Department of Ultrasound, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Qiyu Zhao
- Department of Ultrasound, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Chang He
- Department of Ultrasound, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Yuwei Pan
- Department of Ultrasound, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Feng Xu
- Department of Infectious Diseases, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Tianna Jiang
- Department of Ultrasound, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.,Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China
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9
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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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Electrical Stimulation-Mediated Tissue Healing in Porcine Intervertebral Disc Under Mechanically Dynamic Organ Culture Conditions. Spine (Phila Pa 1976) 2022; 47:764-772. [PMID: 35102117 DOI: 10.1097/brs.0000000000004331] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
STUDY DESIGN Porcine intervertebral discs (IVDs) were excised and then drilled to simulate degeneration before being electrically stimulated for 21 days while undergoing mechanical loading. The discs were then analyzed for gene expression and morphology to assess regeneration. OBJECTIVE The purpose of this study was to investigate the effectiveness of the electrical stimulation of IVD treatment as an early intervention method in halting the progression of degenerative disc disease using an ex-vivo porcine model. SUMMARY OF BACKGROUND DATA Treatments for degenerative disc disease are limited in their efficacy and tend to treat the symptoms of the disease rather than repairing the degenerated disc itself. There is a dire need for an early intervention treatment that not only halts the progression of the disease but contributes to reviving the degenerated disc. METHODS Lumbar IVDs were extracted from a mature pig within 1 hour of death and were drilled with a 1.5 mm bit to simulate degenerative disc disease. Four IVDs at a time were then cultured in a dynamic bioreactor system under mechanical loading for 21 days, two with and two without the electrical stimulation treatment. The IVDs were assessed using histological analysis, magnetic resonance imaging, and quantitative reverse transcriptase polymerase chain reaction to quantify the effectiveness of the treatment on the degenerated discs. RESULTS IVDs with electrical stimulation treatment exhibited extensive annular regeneration and prevented herniation of the nucleus pulposus (NP). In contrast, the untreated group of IVDs were unable to maintain tissue integrity and exhibited NP herniation through multiple layers of the annulus fibrosus. Gene expression showed an increase of extracellular matrix markers and antiinflammatory cytokine interleukin-4 (IL-4), while decreasing in pro-inflammatory markers and pain markers in electrically stimulated IVDs when compared to the untreated group. CONCLUSION The direct electrical stimulation application in NP of damaged IVDs can be a viable option to regenerate damaged NP and annulus fibrosus tissues.
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Li K, Fan L, Lin J, Heng BC, Deng Z, Zheng Q, Zhang J, Jiang Y, Ge Z. Nanosecond pulsed electric fields prime mesenchymal stem cells to peptide ghrelin and enhance chondrogenesis and osteochondral defect repair in vivo. SCIENCE CHINA. LIFE SCIENCES 2022; 65:927-939. [PMID: 34586575 DOI: 10.1007/s11427-021-1983-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 07/22/2021] [Indexed: 01/07/2023]
Abstract
Mesenchymal stem cells (MSCs) are important cell sources in cartilage tissue development and homeostasis, and multiple strategies have been developed to improve MSCs chondrogenic differentiation with an aim of promoting cartilage regeneration. Here we report the effects of combining nanosecond pulsed electric fields (nsPEFs) followed by treatment with ghrelin (a hormone that stimulates release of growth hormone) to regulate chondrogenesis of MSCs. nsPEFs and ghrelin were observed to separately enhance the chondrogenesis of MSCs, and the effects were significantly enhanced when the bioelectric stimulation and hormone were combined, which in turn improved osteochondral tissue repair of these cells within Sprague Dawley rats. We further found that nsPEFs can prime MSCs to be more receptive to subsequent stimuli of differentiation by upregulated Oct4/Nanog and activated JNK signaling pathway. Ghrelin initiated chondrogenic differentiation by activation of ERK1/2 signaling pathway, and RNA-seq results indicated 243 genes were regulated, and JAK-STAT signaling pathway was involved. Interestingly, the sequential order of applying these two stimuli is critical, with nsPEFs pretreatment followed by ghrelin enhanced chondrogenesis of MSCs in vitro and subsequent cartilage regeneration in vivo, but not vice versa. This synergistic prochondrogenic effects provide us new insights and strategies for future cell-based therapies.
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Affiliation(s)
- Kejia Li
- Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, 100871, China
| | - Litong Fan
- Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, 100871, China
| | - Jianjing Lin
- Arthritis Clinical and Research Center, Peking University People's Hospital, Beijing, 100044, China
- Arthritis Institute, Peking University, Beijing, 100871, China
| | - Boon Chin Heng
- Peking University School of Stomatology, Beijing, 100081, China
| | - Zhantao Deng
- Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China
| | - Qiujian Zheng
- Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China
| | - Jue Zhang
- Institute of Biomechanics and Biomedical Engineering, College of Engineering, Peking University, Beijing, 100871, China
| | - Yangzi Jiang
- Institute for Tissue Engineering and Regenerative Medicine, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, 999077, China.
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, 999077, China.
| | - Zigang Ge
- Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, 100871, China.
- Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, 100871, China.
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Zha K, Tian Y, Panayi AC, Mi B, Liu G. Recent Advances in Enhancement Strategies for Osteogenic Differentiation of Mesenchymal Stem Cells in Bone Tissue Engineering. Front Cell Dev Biol 2022; 10:824812. [PMID: 35281084 PMCID: PMC8904963 DOI: 10.3389/fcell.2022.824812] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 02/08/2022] [Indexed: 12/12/2022] Open
Abstract
Although bone is an organ that displays potential for self-healing after damage, bone regeneration does not occur properly in some cases, and it is still a challenge to treat large bone defects. The development of bone tissue engineering provides a new approach to the treatment of bone defects. Among various cell types, mesenchymal stem cells (MSCs) represent one of the most promising seed cells in bone tissue engineering due to their functions of osteogenic differentiation, immunomodulation, and secretion of cytokines. Regulation of osteogenic differentiation of MSCs has become an area of extensive research over the past few years. This review provides an overview of recent research progress on enhancement strategies for MSC osteogenesis, including improvement in methods of cell origin selection, culture conditions, biophysical stimulation, crosstalk with macrophages and endothelial cells, and scaffolds. This is favorable for further understanding MSC osteogenesis and the development of MSC-based bone tissue engineering.
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Affiliation(s)
- Kangkang Zha
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, China
| | - Yue Tian
- Department of Military Patient Management, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Institute of Orthopaedics, Chinese PLA General Hospital, Beijing, China
| | - Adriana C. Panayi
- Division of Plastic Surgery, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, United States
| | - Bobin Mi
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, China
- *Correspondence: Bobin Mi, ; Guohui Liu,
| | - Guohui Liu
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, China
- *Correspondence: Bobin Mi, ; Guohui Liu,
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Distler T, Polley C, Shi F, Schneidereit D, Ashton MD, Friedrich O, Kolb JF, Hardy JG, Detsch R, Seitz H, Boccaccini AR. Electrically Conductive and 3D-Printable Oxidized Alginate-Gelatin Polypyrrole:PSS Hydrogels for Tissue Engineering. Adv Healthc Mater 2021; 10:e2001876. [PMID: 33711199 PMCID: PMC11469227 DOI: 10.1002/adhm.202001876] [Citation(s) in RCA: 64] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Revised: 01/26/2021] [Indexed: 02/06/2023]
Abstract
Electroactive hydrogels can be used to influence cell response and maturation by electrical stimulation. However, hydrogel formulations which are 3D printable, electroactive, cytocompatible, and allow cell adhesion, remain a challenge in the design of such stimuli-responsive biomaterials for tissue engineering. Here, a combination of pyrrole with a high gelatin-content oxidized alginate-gelatin (ADA-GEL) hydrogel is reported, offering 3D-printability of hydrogel precursors to prepare cytocompatible and electrically conductive hydrogel scaffolds. By oxidation of pyrrole, electroactive polypyrrole:polystyrenesulfonate (PPy:PSS) is synthesized inside the ADA-GEL matrix. The hydrogels are assessed regarding their electrical/mechanical properties, 3D-printability, and cytocompatibility. It is possible to prepare open-porous scaffolds via bioplotting which are electrically conductive and have a higher cell seeding efficiency in scaffold depth in comparison to flat 2D hydrogels, which is confirmed via multiphoton fluorescence microscopy. The formation of an interpenetrating polypyrrole matrix in the hydrogel matrix increases the conductivity and stiffness of the hydrogels, maintaining the capacity of the gels to promote cell adhesion and proliferation. The results demonstrate that a 3D-printable ADA-GEL can be rendered conductive (ADA-GEL-PPy:PSS), and that such hydrogel formulations have promise for cell therapies, in vitro cell culture, and electrical-stimulation assisted tissue engineering.
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Affiliation(s)
- Thomas Distler
- Institute of BiomaterialsDepartment of Material Science and EngineeringFriedrich‐Alexander‐University Erlangen‐NurembergErlangen91058Germany
| | - Christian Polley
- Chair of MicrofluidicsDepartment of Mechanical EngineeringUniversity of RostockRostock18059Germany
| | - Fukun Shi
- Leibniz Institute for Plasma Science and Technology (INP)Greifswald17489Germany
| | - Dominik Schneidereit
- Institute of Medical BiotechnologyDepartment of Chemical and Biological EngineeringErlangen91052Germany
| | - Mark. D. Ashton
- Department of ChemistryFaraday BuildingLancaster UniversityLancasterLancashireLA1 4YBUK
- Materials Science InstituteFaraday BuildingLancaster UniversityLancasterLancashireLA1 4YBUK
| | - Oliver Friedrich
- Institute of Medical BiotechnologyDepartment of Chemical and Biological EngineeringErlangen91052Germany
| | - Jürgen F. Kolb
- Leibniz Institute for Plasma Science and Technology (INP)Greifswald17489Germany
| | - John G. Hardy
- Department of ChemistryFaraday BuildingLancaster UniversityLancasterLancashireLA1 4YBUK
- Materials Science InstituteFaraday BuildingLancaster UniversityLancasterLancashireLA1 4YBUK
| | - Rainer Detsch
- Institute of BiomaterialsDepartment of Material Science and EngineeringFriedrich‐Alexander‐University Erlangen‐NurembergErlangen91058Germany
| | - Hermann Seitz
- Chair of MicrofluidicsDepartment of Mechanical EngineeringUniversity of RostockRostock18059Germany
| | - Aldo R. Boccaccini
- Institute of BiomaterialsDepartment of Material Science and EngineeringFriedrich‐Alexander‐University Erlangen‐NurembergErlangen91058Germany
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Recent Developed Strategies for Enhancing Chondrogenic Differentiation of MSC: Impact on MSC-Based Therapy for Cartilage Regeneration. Stem Cells Int 2021; 2021:8830834. [PMID: 33824665 PMCID: PMC8007380 DOI: 10.1155/2021/8830834] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 02/20/2021] [Accepted: 03/04/2021] [Indexed: 12/19/2022] Open
Abstract
Articular cartilage is susceptible to damage, but its self-repair is hindered by its avascular nature. Traditional treatment methods are not able to achieve satisfactory repair effects, and the development of tissue engineering techniques has shed new light on cartilage regeneration. Mesenchymal stem cells (MSCs) are one of the most commonly used seed cells in cartilage tissue engineering. However, MSCs tend to lose their multipotency, and the composition and structure of cartilage-like tissues formed by MSCs are far from those of native cartilage. Thus, there is an urgent need to develop strategies that promote MSC chondrogenic differentiation to give rise to durable and phenotypically correct regenerated cartilage. This review provides an overview of recent advances in enhancement strategies for MSC chondrogenic differentiation, including optimization of bioactive factors, culture conditions, cell type selection, coculture, gene editing, scaffolds, and physical stimulation. This review will aid the further understanding of the MSC chondrogenic differentiation process and enable improvement of MSC-based cartilage tissue engineering.
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Farooqi AR, Zimmermann J, Bader R, van Rienen U. Computational study on electromechanics of electroactive hydrogels for cartilage-tissue repair. COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE 2020; 197:105739. [PMID: 32950923 DOI: 10.1016/j.cmpb.2020.105739] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Accepted: 08/31/2020] [Indexed: 06/11/2023]
Abstract
BACKGROUND AND OBJECTIVE The self-repair capability of articular cartilage is limited because of non-vascularization and low turnover of its extracellular matrix. Regenerating hyaline cartilage remains a significant clinical challenge as most non-surgical and surgical treatments provide only mid-term relief. Eventually, further pain and mobility loss occur for many patients in the long run due to further joint deterioration. Repair of articular cartilage tissue using electroactive scaffolds and biophysical stimuli like electrical and osmotic stimulation may have the potential to heal cartilage defects occurring due to trauma, osteoarthritis, or sport-related injuries. Therefore, the focus of the current study is to present a computational model of electroactive hydrogels for the cartilage-tissue repair as a first step towards an optimized experimental design. METHODS The multiphysics transport model that mainly includes the Poisson-Nernst-Planck equations and the mechanical equation is used to find the electrical stimulation response of the polyelectrolyte hydrogels. Based upon this, a numerical model on electromechanics of electroactive hydrogels seeded with chondrocytes is presented employing the open-source software FEniCS, which is a Python library for finite-element analysis. RESULTS We analyzed the ionic concentrations and electric potential in a hydrogel sample and the cell culture medium, the osmotic pressure created due to ionic concentration variations and the resulting hydrogel displacement. The proposed mathematical model was validated with examples from literature. CONCLUSIONS The presented model for the electrical and osmotic stimulation of a hydrogel sample can serve as a useful tool for the development and analysis of a cartilaginous scaffold employing electrical stimulation. By analyzing various parameters, we pave the way for future research on a finer scale using open-source software.
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Affiliation(s)
- Abdul Razzaq Farooqi
- Institute of General Electrical Engineering, Faculty of Computer Science and Electrical Engineering, University of Rostock, Albert Einstein Str. 2, Rostock 18059, Germany; Department of Electronic Engineering, Faculty of Engineering, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
| | - Julius Zimmermann
- Institute of General Electrical Engineering, Faculty of Computer Science and Electrical Engineering, University of Rostock, Albert Einstein Str. 2, Rostock 18059, Germany
| | - Rainer Bader
- Department of Orthopaedics, University Medical Center Rostock, Rostock 18057, Germany; Department Life, Light & Matter, University of Rostock, Rostock 18051, Germany
| | - Ursula van Rienen
- Institute of General Electrical Engineering, Faculty of Computer Science and Electrical Engineering, University of Rostock, Albert Einstein Str. 2, Rostock 18059, Germany; Department Life, Light & Matter, University of Rostock, Rostock 18051, Germany
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Li K, Ning T, Wang H, Jiang Y, Zhang J, Ge Z. Nanosecond pulsed electric fields enhance mesenchymal stem cells differentiation via DNMT1-regulated OCT4/NANOG gene expression. Stem Cell Res Ther 2020; 11:308. [PMID: 32698858 PMCID: PMC7374836 DOI: 10.1186/s13287-020-01821-5] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Revised: 06/25/2020] [Accepted: 07/09/2020] [Indexed: 02/28/2023] Open
Abstract
Background Multiple strategies have been proposed to promote the differentiation potential of mesenchymal stem cells (MSCs), which is the fundamental property in tissue formation and regeneration. However, these strategies are relatively inefficient that limit the application. In this study, we reported a novel and efficient strategy, nanosecond pulsed electric fields (nsPEFs) stimulation, which can enhance the trilineage differentiation potential of MSCs, and further explained the mechanism behind. Methods We used histological staining to screen out the nsPEFs parameters that promoted the trilineage differentiation potential of MSCs, and further proved the effect of nsPEFs by detecting the functional genes. In order to explore the corresponding mechanism, we examined the expression of pluripotency genes and the methylation status of their promoters. Finally, we targeted the DNA methyltransferase which was affected by nsPEFs. Results The trilineage differentiation of bone marrow-derived MSCs was significantly enhanced in vitro by simply pre-treating with 5 pulses of nsPEFs stimulation (energy levels as 10 ns, 20 kV/cm; 100 ns, 10 kV/cm), due to that the nsPEFs demethylated the promoters of stem cell pluripotency genes OCT4 and NANOG through instantaneous downregulation of DNA methylation transferase 1 (DNMT1), thereby increasing the expression of OCT4 and NANOG for up to 3 days, and created a treatment window period of stem cells. Conclusions In summary, nsPEFs can enhance MSCs differentiation via the epigenetic regulation and could be a safe and effective strategy for future stem cell application.
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Affiliation(s)
- Kejia Li
- Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, 100871, China
| | - Tong Ning
- Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, 100871, China
| | - Hao Wang
- Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China
| | - Yangzi Jiang
- Institute for Tissue Engineering and Regenerative Medicine, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China.,School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Jue Zhang
- Institute of Biomechanics and Biomedical Engineering, College of Engineering, Peking University, Beijing, China
| | - Zigang Ge
- Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, 100871, China.
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Chen J, Huang Y, Yang J, Li K, Jiang Y, Heng BC, Cai Q, Zhang J, Ge Z. Multiple nanosecond pulsed electric fields stimulation with conductive poly(
l
‐lactic acid)/carbon nanotubes films maintains the multipotency of mesenchymal stem cells during prolonged in vitro culture. J Tissue Eng Regen Med 2020; 14:1136-1148. [DOI: 10.1002/term.3088] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Revised: 06/03/2020] [Accepted: 06/06/2020] [Indexed: 12/19/2022]
Affiliation(s)
- Jiaqing Chen
- Department of Biomedical Engineering, College of EngineeringPeking University Beijing China
| | - Yiqian Huang
- State Key Laboratory of Organic‐Inorganic Composites, Beijing Laboratory of Biomedical MaterialsBeijing University of Chemical Technology Beijing China
| | - Jiabei Yang
- Department of Biomedical Engineering, College of EngineeringPeking University Beijing China
| | - Kejia Li
- Department of Biomedical Engineering, College of EngineeringPeking University Beijing China
| | - Yangzi Jiang
- Institute for Tissue Engineering and Regenerative Medicine, School of Biomedical Sciences, Faculty of MedicineThe Chinese University of Hong Kong Hong Kong China
| | - Boon Chin Heng
- Central LaboratoryPeking University School of Stomatology Beijing Beijing China
| | - Qing Cai
- State Key Laboratory of Organic‐Inorganic Composites, Beijing Laboratory of Biomedical MaterialsBeijing University of Chemical Technology Beijing China
| | - Jue Zhang
- Academy for Advanced Interdisciplinary StudiesPeking University Beijing China
| | - Zigang Ge
- Department of Biomedical Engineering, College of EngineeringPeking University Beijing China
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Leppik L, Oliveira KMC, Bhavsar MB, Barker JH. Electrical stimulation in bone tissue engineering treatments. Eur J Trauma Emerg Surg 2020; 46:231-244. [PMID: 32078704 PMCID: PMC7113220 DOI: 10.1007/s00068-020-01324-1] [Citation(s) in RCA: 128] [Impact Index Per Article: 25.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Accepted: 02/04/2020] [Indexed: 12/20/2022]
Abstract
Electrical stimulation (EStim) has been shown to promote bone healing and regeneration both in animal experiments and clinical treatments. Therefore, incorporating EStim into promising new bone tissue engineering (BTE) therapies is a logical next step. The goal of current BTE research is to develop combinations of cells, scaffolds, and chemical and physical stimuli that optimize treatment outcomes. Recent studies demonstrating EStim's positive osteogenic effects at the cellular and molecular level provide intriguing clues to the underlying mechanisms by which it promotes bone healing. In this review, we discuss results of recent in vitro and in vivo research focused on using EStim to promote bone healing and regeneration and consider possible strategies for its application to improve outcomes in BTE treatments. Technical aspects of exposing cells and tissues to EStim in in vitro and in vivo model systems are also discussed.
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Affiliation(s)
- Liudmila Leppik
- Frankfurt Initiative for Regenerative Medicine, Experimental Orthopedics and Trauma Surgery, J.W. Goethe University, Frankfurt/Main, Germany.
| | - Karla Mychellyne Costa Oliveira
- Frankfurt Initiative for Regenerative Medicine, Experimental Orthopedics and Trauma Surgery, J.W. Goethe University, Frankfurt/Main, Germany
| | - Mit Balvantray Bhavsar
- Frankfurt Initiative for Regenerative Medicine, Experimental Orthopedics and Trauma Surgery, J.W. Goethe University, Frankfurt/Main, Germany
| | - John Howard Barker
- Frankfurt Initiative for Regenerative Medicine, Experimental Orthopedics and Trauma Surgery, J.W. Goethe University, Frankfurt/Main, Germany
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