1
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Borah R, O'Sullivan J, Suku M, Spurling D, Diez Clarke D, Nicolosi V, Caldwell MA, Monaghan MG. Electrically Conductive Injectable Silk/PEDOT: PSS Hydrogel for Enhanced Neural Network Formation. J Biomed Mater Res A 2025; 113:e37859. [PMID: 39719872 DOI: 10.1002/jbm.a.37859] [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: 08/07/2024] [Revised: 12/06/2024] [Accepted: 12/12/2024] [Indexed: 12/26/2024]
Abstract
With no effective treatments for functional recovery after injury, spinal cord injury (SCI) remains one of the unresolved healthcare challenges. Human induced pluripotent stem cell (hiPSC) transplantation is a versatile patient-specific regenerative approach for functional recovery after SCI. Injectable electroconductive hydrogel (ECH) can further enhance the cell transplantation efficacy through a minimally invasive manner as well as recapitulate the native bioelectrical microenvironment of neural tissue. Given these considerations, we report a novel ECH prepared through self-assembly facilitated in situ gelation of natural silk fibroin (SF) derived from mulberry Bombyx mori silk and electrically conductive PEDOT:PSS. PEDOT:PSS was pre-stabilized to prevent the potential delamination of its hydrophilic PSS chain under aqueous environment using 3% (v/v) (3-glycidyloxypropyl)trimethoxysilane (GoPS) and 3% (w/v) poly(ethylene glycol)diglycidyl ether (PeGDE). The resultant ECH formulations are easily injectable with standard hand force with flow point below 100 Pa and good shear-thinning properties. The ECH formulations with unmodified and GoPS-modified PEDOT:PSS, that is, SF/PEDOT and SF/PEDOTGoP maintain comparable elastic modulus to spinal cord (~10-60 kPa) under physiological condition, indicating their flexibility. The GoPS-modified ECHs also display improved structural recoverability (~70%-90%) as compared to the unmodified versions of the ECHs (~30%-80%), as indicated by the three interval time thixotropy (3ITT) test. Additionally, these ECHs possess electrical conductivity in the range of ~0.2-1.2 S/m comparable to spinal cord (1-10 S/m), indicating their ability to mimic native bioelectrical environment. Approximately 80% or more cell survival was observed when hiPSC-derived cortical neurons and astrocytes were encapsulated within these ECHs. These ECHs support the maturation of cortical neurons when embedded for 7 days, fostering the development of a complex, interconnected network of long axonal processes and promoting synaptogenesis. These results underline the potential of silk ECHs in cell transplantation therapy for spinal cord regeneration.
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Affiliation(s)
- Rajiv Borah
- Discipline of Mechanical, Manufacturing and Biomedical Engineering, Trinity College Dublin, Dublin 2, Ireland
- Trinity Centre for Biomedical Engineering, Trinity College Dublin, Dublin 2, Ireland
- Advanced Materials and Bio-Engineering Research (AMBER), Centre at Trinity College Dublin and the Royal College of Surgeons in Ireland, Dublin 2, Ireland
| | - Julia O'Sullivan
- Department of Physiology, School of Medicine, Trinity College Dublin, Dublin 2, Ireland
- Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland
| | - Meenakshi Suku
- Discipline of Mechanical, Manufacturing and Biomedical Engineering, Trinity College Dublin, Dublin 2, Ireland
- Trinity Centre for Biomedical Engineering, Trinity College Dublin, Dublin 2, Ireland
| | - Dahnan Spurling
- Advanced Materials and Bio-Engineering Research (AMBER), Centre at Trinity College Dublin and the Royal College of Surgeons in Ireland, Dublin 2, Ireland
- Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College Dublin, Dublin 2, Ireland
- School of Chemistry, Trinity College Dublin, Dublin 2, Ireland
| | - Daniel Diez Clarke
- Discipline of Mechanical, Manufacturing and Biomedical Engineering, Trinity College Dublin, Dublin 2, Ireland
- Trinity Centre for Biomedical Engineering, Trinity College Dublin, Dublin 2, Ireland
| | - Valeria Nicolosi
- Advanced Materials and Bio-Engineering Research (AMBER), Centre at Trinity College Dublin and the Royal College of Surgeons in Ireland, Dublin 2, Ireland
- Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College Dublin, Dublin 2, Ireland
- School of Chemistry, Trinity College Dublin, Dublin 2, Ireland
| | - Maeve A Caldwell
- Department of Physiology, School of Medicine, Trinity College Dublin, Dublin 2, Ireland
- Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland
| | - Michael G Monaghan
- Discipline of Mechanical, Manufacturing and Biomedical Engineering, Trinity College Dublin, Dublin 2, Ireland
- Trinity Centre for Biomedical Engineering, Trinity College Dublin, Dublin 2, Ireland
- Advanced Materials and Bio-Engineering Research (AMBER), Centre at Trinity College Dublin and the Royal College of Surgeons in Ireland, Dublin 2, Ireland
- CÚRAM, Research Ireland Centre for Research in Medical Devices, National University of Ireland, Galway, Ireland
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2
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Peñas-Núñez S, Mecerreyes D, Criado-Gonzalez M. Recent Advances and Developments in Injectable Conductive Polymer Gels for Bioelectronics. ACS APPLIED BIO MATERIALS 2024; 7:7944-7964. [PMID: 38364213 PMCID: PMC11653406 DOI: 10.1021/acsabm.3c01224] [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: 12/12/2023] [Revised: 01/30/2024] [Accepted: 01/31/2024] [Indexed: 02/18/2024]
Abstract
Soft matter bioelectronics represents an emerging and interdisciplinary research frontier aiming to harness the synergy between biology and electronics for advanced diagnostic and healthcare applications. In this context, a whole family of soft gels have been recently developed with self-healing ability and tunable biological mimetic features to act as a tissue-like space bridging the interface between the electronic device and dynamic biological fluids and body tissues. This review article provides a comprehensive overview of electroactive polymer gels, formed by noncovalent intermolecular interactions and dynamic covalent bonds, as injectable electroactive gels, covering their synthesis, characterization, and applications. First, hydrogels crafted from conducting polymers (poly(3,4-ethylene-dioxythiophene) (PEDOT), polyaniline (PANi), and polypyrrole (PPy))-based networks which are connected through physical interactions (e.g., hydrogen bonding, π-π stacking, hydrophobic interactions) or dynamic covalent bonds (e.g., imine bonds, Schiff-base, borate ester bonds) are addressed. Injectable hydrogels involving hybrid networks of polymers with conductive nanomaterials (i.e., graphene oxide, carbon nanotubes, metallic nanoparticles, etc.) are also discussed. Besides, it also delves into recent advancements in injectable ionic liquid-integrated gels (iongels) and deep eutectic solvent-integrated gels (eutectogels), which present promising avenues for future research. Finally, the current applications and future prospects of injectable electroactive polymer gels in cutting-edge bioelectronic applications ranging from tissue engineering to biosensing are outlined.
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Affiliation(s)
- Sergio
J. Peñas-Núñez
- POLYMAT,
University of the Basque Country UPV/EHU, Avda. Tolosa 72, 20018 Donostia-San Sebastián, Spain
| | - David Mecerreyes
- POLYMAT,
University of the Basque Country UPV/EHU, Avda. Tolosa 72, 20018 Donostia-San Sebastián, Spain
- Ikerbasque,
Basque Foundation for Science, 48013 Bilbao, Spain
| | - Miryam Criado-Gonzalez
- POLYMAT,
University of the Basque Country UPV/EHU, Avda. Tolosa 72, 20018 Donostia-San Sebastián, Spain
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3
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Casella A, Lowen J, Griffin KH, Shimamoto N, Ramos-Rodriguez DH, Panitch A, Leach JK. Conductive Microgel Annealed Scaffolds Enhance Myogenic Potential of Myoblastic Cells. Adv Healthc Mater 2024; 13:e2302500. [PMID: 38069833 PMCID: PMC11759339 DOI: 10.1002/adhm.202302500] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 11/15/2023] [Indexed: 12/19/2023]
Abstract
Conductive biomaterials may capture native or exogenous bioelectric signaling, but incorporation of conductive moieties is limited by cytotoxicity, poor injectability, or insufficient stimulation. Microgel annealed scaffolds are promising as hydrogel-based materials due to their inherent void space that facilitates cell migration and proliferation better than nanoporous bulk hydrogels. Conductive microgels are generated from poly(ethylene) glycol (PEG and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT: PSS) to explore the interplay of void volume and conductivity on myogenic differentiation. PEDOT: PSS increases microgel conductivity two-fold while maintaining stiffness, annealing strength, and viability of associated myoblastic cells. C2C12 myoblasts exhibit increases in the late-stage differentiation marker myosin heavy chain as a function of both porosity and conductivity. Myogenin, an earlier marker, is influenced only by porosity. Human skeletal muscle-derived cells exhibit increased Myod1, insulin like growth factor-1, and insulin-like growth factor binding protein 2 at earlier time points on conductive microgel scaffolds compared to non-conductive scaffolds. They also secrete more vascular endothelial growth factor at early time points and express factors that led to macrophage polarization patterns observe during muscle repair. These data indicate that conductivity aids myogenic differentiation of myogenic cell lines and primary cells, motivating the need for future translational studies to promote muscle repair.
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Affiliation(s)
- Alena Casella
- Department of Biomedical Engineering, University of California Davis, Davis, CA 95616
- Department of Orthopaedic Surgery, School of Medicine, UC Davis Health, Sacramento, CA 95817
| | - Jeremy Lowen
- Department of Biomedical Engineering, University of California Davis, Davis, CA 95616
- Department of Orthopaedic Surgery, School of Medicine, UC Davis Health, Sacramento, CA 95817
| | - Katherine H. Griffin
- Department of Orthopaedic Surgery, School of Medicine, UC Davis Health, Sacramento, CA 95817
- School of Veterinary Medicine, University of California, Davis, Davis, CA 95616
| | - Nathan Shimamoto
- Department of Biomedical Engineering, University of California Davis, Davis, CA 95616
- Department of Orthopaedic Surgery, School of Medicine, UC Davis Health, Sacramento, CA 95817
| | | | - Alyssa Panitch
- Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332
- Department of Biomedical Engineering, Emory University, Atlanta, GA 30322
| | - J. Kent Leach
- Department of Biomedical Engineering, University of California Davis, Davis, CA 95616
- Department of Orthopaedic Surgery, School of Medicine, UC Davis Health, Sacramento, CA 95817
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4
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Kusen I, Lee A, Cuttaz EA, Bailey ZK, Killilea J, Aslie SMN, Goding JA, Green RA. Injectable conductive hydrogel electrodes for minimally invasive neural interfaces. J Mater Chem B 2024; 12:8929-8940. [PMID: 39145569 PMCID: PMC11325676 DOI: 10.1039/d4tb00679h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Accepted: 07/22/2024] [Indexed: 08/16/2024]
Abstract
Soft bioelectronic neural interfaces have great potential as mechanically favourable alternatives to implantable metal electrodes. In this pursuit, conductive hydrogels (CHs) are particularly viable, combining tissue compliance with the required electrochemical characteristics. Physically-aggregated CHs offer an additional advantage by their facile synthesis into injectable systems, enabling minimally invasive implantation, though they can be impeded by a lack of control over their particle size and packing. Guided by these principles, an injectable PEDOT:PSS/acetic acid-based hydrogel is presented herein whose mechanical and electrochemical properties are independently tuneable by modifying the relative acetic acid composition. The fabrication process further benefits from employing batch emulsion to decrease particle sizes and facilitate tighter packing. The resulting material is stable and anatomically compact upon injection both in tissue phantom and ex vivo, while retaining favourable electrochemical properties in both contexts. Biphasic current stimulation yielding voltage transients well below the charge injection limit as well as the gel's non-cytotoxicity further underscore its potential for safe and effective neural interfacing applications.
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Affiliation(s)
- Ines Kusen
- Department of Bioengineering, Imperial College London, London, SW7 2BX, UK.
| | - Aaron Lee
- Department of Bioengineering, Imperial College London, London, SW7 2BX, UK.
| | - Estelle A Cuttaz
- Department of Bioengineering, Imperial College London, London, SW7 2BX, UK.
| | - Zachary K Bailey
- Department of Bioengineering, Imperial College London, London, SW7 2BX, UK.
| | - Joshua Killilea
- Department of Bioengineering, Imperial College London, London, SW7 2BX, UK.
- Faculty of Medicine, Imperial College London, London, SW7 2BX, UK
| | | | - Josef A Goding
- Department of Bioengineering, Imperial College London, London, SW7 2BX, UK.
| | - Rylie A Green
- Department of Bioengineering, Imperial College London, London, SW7 2BX, UK.
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5
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Fatima R, Almeida B. Methods to achieve tissue-mimetic physicochemical properties in hydrogels for regenerative medicine and tissue engineering. J Mater Chem B 2024; 12:8505-8522. [PMID: 39149830 DOI: 10.1039/d4tb00716f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/17/2024]
Abstract
Hydrogels are water-swollen polymeric matrices with properties that are remarkably similar in function to the extracellular matrix. For example, the polymer matrix provides structural support and adhesion sites for cells in much of the same way as the fibers of the extracellular matrix. In addition, depending on the polymer used, bioactive sites on the polymer may provide signals to initiate certain cell behavior. However, despite their potential as biomaterials for tissue engineering and regenerative medicine applications, fabricating hydrogels that truly mimic the physicochemical properties of the extracellular matrix to physiologically-relevant values is a challenge. Recent efforts in the field have sought to improve the physicochemical properties of hydrogels using advanced materials science and engineering methods. In this review, we highlight some of the most promising methods, including crosslinking strategies and manufacturing approaches such as 3D bioprinting and granular hydrogels. We also provide a brief perspective on the future outlook of this field and how these methods may lead to the clinical translation of hydrogel biomaterials for tissue engineering and regenerative medicine applications.
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Affiliation(s)
- Rabia Fatima
- Department of Chemical and Biomolecular Engineering, Clarkson University, Potsdam, NY 13699, USA.
| | - Bethany Almeida
- Department of Chemical and Biomolecular Engineering, Clarkson University, Potsdam, NY 13699, USA.
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6
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Han GY, Kwack HW, Kim YH, Je YH, Kim HJ, Cho CS. Progress of polysaccharide-based tissue adhesives. Carbohydr Polym 2024; 327:121634. [PMID: 38171653 DOI: 10.1016/j.carbpol.2023.121634] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Revised: 11/20/2023] [Accepted: 11/21/2023] [Indexed: 01/05/2024]
Abstract
Recently, polymer-based tissue adhesives (TAs) have gained the attention of scientists and industries as alternatives to sutures for sealing and closing wounds or incisions because of their ease of use, low cost, minimal tissue damage, and short application time. However, poor mechanical properties and weak adhesion strength limit the application of TAs, although numerous studies have attempted to develop new TAs with enhanced performance. Therefore, next-generation TAs with improved multifunctional properties are required. In this review, we address the requirements of polymeric TAs, adhesive characteristics, adhesion strength assessment methods, adhesion mechanisms, applications, advantages and disadvantages, and commercial products of polysaccharide (PS)-based TAs, including chitosan (CS), alginate (AL), dextran (DE), and hyaluronic acid (HA). Additionally, future perspectives are discussed.
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Affiliation(s)
- Gi-Yeon Han
- Program in Environmental Materials Science, Department of Agriculture, Forestry and Bioresources, Seoul National University, Seoul 08826, Republic of Korea
| | - Ho-Wook Kwack
- Program in Environmental Materials Science, Department of Agriculture, Forestry and Bioresources, Seoul National University, Seoul 08826, Republic of Korea
| | - Yo-Han Kim
- Department of Agricultural Biotechnology, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea
| | - Yeon Ho Je
- Department of Agricultural Biotechnology, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea
| | - Hyun-Joong Kim
- Program in Environmental Materials Science, Department of Agriculture, Forestry and Bioresources, Seoul National University, Seoul 08826, Republic of Korea.
| | - Chong-Su Cho
- Department of Agricultural Biotechnology, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea.
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7
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Song S, McConnell KW, Shan D, Chen C, Oh B, Sun J, Poon ASY, George PM. Conductive gradient hydrogels allow spatial control of adult stem cell fate. J Mater Chem B 2024; 12:1854-1863. [PMID: 38291979 PMCID: PMC10922832 DOI: 10.1039/d3tb02269b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2024]
Abstract
Electrical gradients are fundamental to physiological processes including cell migration, tissue formation, organ development, and response to injury and regeneration. Current electrical modulation of cells is primarily studied under a uniform electrical field. Here we demonstrate the fabrication of conductive gradient hydrogels (CGGs) that display mechanical properties and varying local electrical gradients mimicking physiological conditions. The electrically-stimulated CGGs enhanced human mesenchymal stem cell (hMSC) viability and attachment. Cells on CGGs under electrical stimulation showed a high expression of neural progenitor markers such as Nestin, GFAP, and Sox2. More importantly, CGGs showed cell differentiation toward oligodendrocyte lineage (Oligo2) in the center of the scaffold where the electric field was uniform with a greater intensity, while cells preferred neuronal lineage (NeuN) on the edge of the scaffold on a varying electric field at lower magnitude. Our data suggest that CGGs can serve as a useful platform to study the effects of electrical gradients on stem cells and potentially provide insights on developing new neural engineering applications.
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Affiliation(s)
- Shang Song
- Department of Neurology and Neurological Sciences, Stanford University, School of Medicine, 300 Pasteur Dr, MC5778 Stanford Stroke Center, Stanford, CA 94305-5778, USA.
- Department of Biomedical Engineering, The University of Arizona, Tucson, AZ, USA
- Departments of Neuroscience GIDP, Materials Science and Engineering, BIO5 Institute, The University of Arizona, Tucson, AZ, USA
| | - Kelly W McConnell
- Department of Neurology and Neurological Sciences, Stanford University, School of Medicine, 300 Pasteur Dr, MC5778 Stanford Stroke Center, Stanford, CA 94305-5778, USA.
| | - Dingying Shan
- Department of Neurology and Neurological Sciences, Stanford University, School of Medicine, 300 Pasteur Dr, MC5778 Stanford Stroke Center, Stanford, CA 94305-5778, USA.
| | - Cheng Chen
- Department of Electrical Engineering, Stanford University, Stanford, CA, USA
| | - Byeongtaek Oh
- Department of Neurology and Neurological Sciences, Stanford University, School of Medicine, 300 Pasteur Dr, MC5778 Stanford Stroke Center, Stanford, CA 94305-5778, USA.
| | - Jindi Sun
- Department of Biomedical Engineering, The University of Arizona, Tucson, AZ, USA
| | - Ada S Y Poon
- Department of Electrical Engineering, Stanford University, Stanford, CA, USA
| | - Paul M George
- Department of Neurology and Neurological Sciences, Stanford University, School of Medicine, 300 Pasteur Dr, MC5778 Stanford Stroke Center, Stanford, CA 94305-5778, USA.
- Stanford Stroke Center and Stanford University School of Medicine, Stanford, CA, USA
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8
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Tropp J, Collins CP, Xie X, Daso RE, Mehta AS, Patel SP, Reddy MM, Levin SE, Sun C, Rivnay J. Conducting Polymer Nanoparticles with Intrinsic Aqueous Dispersibility for Conductive Hydrogels. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2306691. [PMID: 37680065 PMCID: PMC11294187 DOI: 10.1002/adma.202306691] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/08/2023] [Revised: 08/16/2023] [Indexed: 09/09/2023]
Abstract
Conductive hydrogels are promising materials with mixed ionic-electronic conduction to interface living tissue (ionic signal transmission) with medical devices (electronic signal transmission). The hydrogel form factor also uniquely bridges the wet/soft biological environment with the dry/hard environment of electronics. The synthesis of hydrogels for bioelectronics requires scalable, biocompatible fillers with high electronic conductivity and compatibility with common aqueous hydrogel formulations/resins. Despite significant advances in the processing of carbon nanomaterials, fillers that satisfy all these requirements are lacking. Herein, intrinsically dispersible acid-crystalized PEDOT:PSS nanoparticles (ncrys-PEDOTX ) are reported which are processed through a facile and scalable nonsolvent induced phase separation method from commercial PEDOT:PSS without complex instrumentation. The particles feature conductivities of up to 410 S cm-1 , and when compared to other common conductive fillers, display remarkable dispersibility, enabling homogeneous incorporation at relatively high loadings within diverse aqueous biomaterial solutions without additives or surfactants. The aqueous dispersibility of the ncrys-PEDOTX particles also allows simple incorporation into resins designed for microstereolithography without sonication or surfactant optimization; complex biomedical structures with fine features (< 150 µm) are printed with up to 10% particle loading . The ncrys-PEDOTX particles overcome the challenges of traditional conductive fillers, providing a scalable, biocompatible, plug-and-play platform for soft organic bioelectronic materials.
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Affiliation(s)
- Joshua Tropp
- Department of Biomedical Engineering, Northwestern University Evanston, IL 60208, USA
| | - Caralyn P. Collins
- Department of Mechanical Engineering Northwestern University, Evanston, IL 60208, USA
| | - Xinran Xie
- Department of Biomedical Engineering, Northwestern University Evanston, IL 60208, USA
| | - Rachel E. Daso
- Department of Biomedical Engineering, Northwestern University Evanston, IL 60208, USA
| | - Abijeet Singh Mehta
- Department of Biomedical Engineering, Northwestern University Evanston, IL 60208, USA
| | - Shiv P. Patel
- Department of Biomedical Engineering, Northwestern University Evanston, IL 60208, USA
| | - Manideep M. Reddy
- Department of Biomedical Engineering, Northwestern University Evanston, IL 60208, USA
| | - Sophia E. Levin
- Department of Mechanical Engineering Northwestern University, Evanston, IL 60208, USA
| | - Cheng Sun
- Department of Mechanical Engineering Northwestern University, Evanston, IL 60208, USA
| | - Jonathan Rivnay
- Department of Biomedical Engineering, Northwestern University Evanston, IL 60208, USA
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9
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Goestenkors AP, Liu T, Okafor SS, Semar BA, Alvarez RM, Montgomery SK, Friedman L, Rutz AL. Manipulation of cross-linking in PEDOT:PSS hydrogels for biointerfacing. J Mater Chem B 2023; 11:11357-11371. [PMID: 37997395 DOI: 10.1039/d3tb01415k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2023]
Abstract
Conducting hydrogels can be used to fabricate bioelectronic devices that are soft for improved cell- and tissue-interfacing. Those based on conjugated polymers, such as poly(3,4-ethylene-dioxythiophene):polystyrene sulfonate (PEDOT:PSS), can be made simply with solution-based processing techniques, yet the influence of fabrication variables on final gel properties is not fully understood. In this study, we investigated if PEDOT:PSS cross-linking could be manipulated by changing the concentration of a gelling agent, ionic liquid, in the hydrogel precursor mixture. Rheology and gelation kinetics of precursor mixtures were investigated, and aqueous stability, swelling, conductivity, stiffness, and cytocompatibility of formed hydrogels were characterized. Increasing ionic liquid concentration was found to increase cross-linking as measured by decreased swelling, decreased non-network fraction, increased stiffness, and increased conductivity. Such manipulation of IL concentration thus afforded control of final gel properties and was utilized in further investigations of biointerfacing. When cross-linked sufficiently, PEDOT:PSS hydrogels were stable in sterile cell culture conditions for at least 28 days. Additionally, hydrogels supported a viable and proliferating population of human dermal fibroblasts for at least two weeks. Collectively, these characterizations of stability and cytocompatibility illustrate that these PEDOT:PSS hydrogels have significant promise for biointerfacing applications that require soft materials for direct interaction with cells.
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Affiliation(s)
- Anna P Goestenkors
- Department of Biomedical Engineering, Washington University in St. Louis, 1 Brookings Dr, St. Louis, MO, USA.
| | - Tianran Liu
- Department of Biomedical Engineering, Washington University in St. Louis, 1 Brookings Dr, St. Louis, MO, USA.
| | - Somtochukwu S Okafor
- Department of Biomedical Engineering, Washington University in St. Louis, 1 Brookings Dr, St. Louis, MO, USA.
| | - Barbara A Semar
- Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, 1 Brookings Dr, St. Louis, MO, USA
| | - Riley M Alvarez
- Department of Biomedical Engineering, Washington University in St. Louis, 1 Brookings Dr, St. Louis, MO, USA.
| | - Sandra K Montgomery
- Department of Biomedical Engineering, Washington University in St. Louis, 1 Brookings Dr, St. Louis, MO, USA.
| | - Lianna Friedman
- Department of Biomedical Engineering, Washington University in St. Louis, 1 Brookings Dr, St. Louis, MO, USA.
| | - Alexandra L Rutz
- Department of Biomedical Engineering, Washington University in St. Louis, 1 Brookings Dr, St. Louis, MO, USA.
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Kim S, Jang J, Kang K, Jin S, Choi H, Son D, Shin M. Injection-on-Skin Granular Adhesive for Interactive Human-Machine Interface. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2023; 35:e2307070. [PMID: 37769671 DOI: 10.1002/adma.202307070] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 09/12/2023] [Indexed: 10/03/2023]
Abstract
Realization of interactive human-machine interfaces (iHMI) is improved with development of soft tissue-like strain sensors beyond hard robotic exosuits, potentially allowing cognitive behavior therapy and physical rehabilitation for patients with brain disorders. Here, this study reports on a strain-sensitive granular adhesive inspired by the core-shell architectures of natural basil seeds for iHMI as well as human-metaverse interfacing. The granular adhesive sensor consists of easily fragmented hydropellets as a core and tissue-adhesive catecholamine layers as a shell, satisfying great on-skin injectability, ionic-electrical conductivity, and sensitive resistance changes through reversible yet robust cohesion among the hydropellets. Particularly, it is found that the ionic-electrical self-doping of the catecholamine shell on hydrosurfaces leads to a compact ion density of the materials. Based on these physical and electrical properties of the sensor, it is demonstrated that successful iHMI integration with a robot arm in both real and virtual environments enables robotic control by finger gesture and haptic feedback. This study expresses benefits of using granular hydrogel-based strain sensors for implementing on-skin writable bioelectronics and their bridging into the metaverse world.
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Affiliation(s)
- Sumin Kim
- Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, 16419, Republic of Korea
- Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Suwon, 16419, Republic of Korea
| | - Jaepyo Jang
- Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Suwon, 16419, Republic of Korea
- Department of Electrical and Computer Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea
| | - Kyumin Kang
- Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Suwon, 16419, Republic of Korea
- Department of Electrical and Computer Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea
| | - Subin Jin
- Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, 16419, Republic of Korea
- Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Suwon, 16419, Republic of Korea
| | - Heewon Choi
- Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Suwon, 16419, Republic of Korea
- Department of Electrical and Computer Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea
| | - Donghee Son
- Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Suwon, 16419, Republic of Korea
- Department of Electrical and Computer Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea
- Department of Artificial Intelligence System Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea
| | - Mikyung Shin
- Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, 16419, Republic of Korea
- Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Suwon, 16419, Republic of Korea
- Department of Biomedical Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea
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11
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Kim SD, Kim K, Shin M. Recent advances in 3D printable conductive hydrogel inks for neural engineering. NANO CONVERGENCE 2023; 10:41. [PMID: 37679589 PMCID: PMC10484881 DOI: 10.1186/s40580-023-00389-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Accepted: 08/23/2023] [Indexed: 09/09/2023]
Abstract
Recently, the 3D printing of conductive hydrogels has undergone remarkable advances in the fabrication of complex and functional structures. In the field of neural engineering, an increasing number of reports have been published on tissue engineering and bioelectronic approaches over the last few years. The convergence of 3D printing methods and electrically conducting hydrogels may create new clinical and therapeutic possibilities for precision regenerative medicine and implants. In this review, we summarize (i) advancements in preparation strategies for conductive materials, (ii) various printing techniques enabling the fabrication of electroconductive hydrogels, (iii) the required physicochemical properties of the printed constructs, (iv) their applications in bioelectronics and tissue regeneration for neural engineering, and (v) unconventional approaches and outlooks for the 3D printing of conductive hydrogels. This review provides technical insights into 3D printable conductive hydrogels and encompasses recent developments, specifically over the last few years of research in the neural engineering field.
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Affiliation(s)
- Sung Dong Kim
- Department of Biomedical Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea
- Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Suwon, 16419, Republic of Korea
| | - Kyoungryong Kim
- Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Suwon, 16419, Republic of Korea
- Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, 16419, Republic of Korea
| | - Mikyung Shin
- Department of Biomedical Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
- Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Suwon, 16419, Republic of Korea.
- Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
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12
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Amirthalingam S, Rajendran AK, Moon YG, Hwang NS. Stimuli-responsive dynamic hydrogels: design, properties and tissue engineering applications. MATERIALS HORIZONS 2023; 10:3325-3350. [PMID: 37387121 DOI: 10.1039/d3mh00399j] [Citation(s) in RCA: 42] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/01/2023]
Abstract
The field of tissue engineering and regenerative medicine has been evolving at a rapid pace with numerous novel and interesting biomaterials being reported. Hydrogels have come a long way in this regard and have been proven to be an excellent choice for tissue regeneration. This could be due to their innate properties such as water retention, and ability to carry and deliver a multitude of therapeutic and regenerative elements to aid in better outcomes. Over the past few decades, hydrogels have been developed into an active and attractive system that can respond to various stimuli, thereby presenting a wider control over the delivery of the therapeutic agents to the intended site in a spatiotemporal manner. Researchers have developed hydrogels that respond dynamically to a multitude of external as well as internal stimuli such as mechanics, thermal energy, light, electric field, ultrasonics, tissue pH, and enzyme levels, to name a few. This review gives a brief overview of the recent developments in such hydrogel systems which respond dynamically to various stimuli, some of the interesting fabrication strategies, and their application in cardiac, bone, and neural tissue engineering.
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Affiliation(s)
- Sivashanmugam Amirthalingam
- Institute of Engineering Research, Seoul National University, Seoul, 08826, Republic of Korea.
- School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul, 08826, Republic of Korea
| | - Arun Kumar Rajendran
- School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul, 08826, Republic of Korea
| | - Young Gi Moon
- School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul, 08826, Republic of Korea
| | - Nathaniel S Hwang
- Institute of Engineering Research, Seoul National University, Seoul, 08826, Republic of Korea.
- School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul, 08826, Republic of Korea
- Interdisciplinary Program in Bioengineering, Seoul National University, Seoul, 08826, Republic of Korea
- Bio-MAX/N-Bio Institute, Institute of Bio-Engineering, Seoul National University, Seoul, 08826, Republic of Korea
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13
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Lyu X, Hu Y, Shi S, Wang S, Li H, Wang Y, Zhou K. Hydrogel Bioelectronics for Health Monitoring. BIOSENSORS 2023; 13:815. [PMID: 37622901 PMCID: PMC10452556 DOI: 10.3390/bios13080815] [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: 06/28/2023] [Revised: 08/07/2023] [Accepted: 08/09/2023] [Indexed: 08/26/2023]
Abstract
Hydrogels are considered an ideal platform for personalized healthcare due to their unique characteristics, such as their outstanding softness, appealing biocompatibility, excellent mechanical properties, etc. Owing to the high similarity between hydrogels and biological tissues, hydrogels have emerged as a promising material candidate for next generation bioelectronic interfaces. In this review, we discuss (i) the introduction of hydrogel and its traditional applications, (ii) the work principles of hydrogel in bioelectronics, (iii) the recent advances in hydrogel bioelectronics for health monitoring, and (iv) the outlook for future hydrogel bioelectronics' development.
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Affiliation(s)
- Xinyan Lyu
- School of Science and Engineering, The Chinese University of Hong Kong, Shenzhen 518172, China; (X.L.); (S.W.); (H.L.)
| | - Yan Hu
- The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710061, China; (Y.H.); (S.S.)
| | - Shuai Shi
- The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710061, China; (Y.H.); (S.S.)
| | - Siyuan Wang
- School of Science and Engineering, The Chinese University of Hong Kong, Shenzhen 518172, China; (X.L.); (S.W.); (H.L.)
| | - Haowen Li
- School of Science and Engineering, The Chinese University of Hong Kong, Shenzhen 518172, China; (X.L.); (S.W.); (H.L.)
| | - Yuheng Wang
- Faculty of Electrical Engineering and Computer Science, Ningbo University, Ningbo 315211, China;
| | - Kun Zhou
- School of Science and Engineering, The Chinese University of Hong Kong, Shenzhen 518172, China; (X.L.); (S.W.); (H.L.)
- The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710061, China; (Y.H.); (S.S.)
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14
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Casella A, Lowen J, Shimamoto N, Griffin KH, Filler AC, Panitch A, Leach JK. Conductive microgel annealed scaffolds enhance myogenic potential of myoblastic cells. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.08.01.551533. [PMID: 37577583 PMCID: PMC10418230 DOI: 10.1101/2023.08.01.551533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/15/2023]
Abstract
Bioelectricity is an understudied phenomenon to guide tissue homeostasis and regeneration. Conductive biomaterials may capture native or exogenous bioelectric signaling, but incorporation of conductive moieties is limited by cytotoxicity, poor injectability, or insufficient stimulation. Microgel annealed scaffolds are promising as hydrogel-based materials due to their inherent void space that facilitates cell migration and proliferation better than nanoporous bulk hydrogels. We generated conductive microgels from poly(ethylene) glycol and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) to explore the interplay of void volume and conductivity on myogenic differentiation. PEDOT:PSS increased microgel conductivity over 2-fold while maintaining stiffness, annealing strength, and viability of associated myoblastic cells. C2C12 myoblasts exhibited increases in the late-stage differentiation marker myosin heavy chain as a function of both porosity and conductivity. Myogenin, an earlier marker, was influenced only by porosity. Human skeletal muscle derived cells exhibited increased Myod1 , IGF-1, and IGFBP-2 at earlier timepoints on conductive microgel scaffolds compared to non-conductive scaffolds. They also secreted higher levels of VEGF at early timepoints and expressed factors that led to macrophage polarization patterns observed during muscle repair. These data indicate that conductivity aids myogenic differentiation of myogenic cell lines and primary cells, motivating the need for future translational studies to promote muscle repair.
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15
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Wang Z, Lin H, Zhang M, Yu W, Zhu C, Wang P, Huang Y, Lv F, Bai H, Wang S. Water-soluble conjugated polymers for bioelectronic systems. MATERIALS HORIZONS 2023; 10:1210-1233. [PMID: 36752220 DOI: 10.1039/d2mh01520j] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/18/2023]
Abstract
Bioelectronics is an interdisciplinary field of research that aims to establish a synergy between electronics and biology. Contributing to a deeper understanding of bioelectronic processes and the built bioelectronic systems, a variety of new phenomena, mechanisms and concepts have been derived in the field of biology, medicine, energy, artificial intelligence science, etc. Organic semiconductors can promote the applications of bioelectronics in improving original performance and creating new features for organisms due to their excellent photoelectric and electrical properties. Recently, water-soluble conjugated polymers (WSCPs) have been employed as a class of ideal interface materials to regulate bioelectronic processes between biological systems and electronic systems, relying on their satisfying ionic conductivity, water-solubility, good biocompatibility and the additional mechanical and electrical properties. In this review, we summarize the prominent contributions of WSCPs in the aspect of the regulation of bioelectronic processes and highlight the latest advances in WSCPs for bioelectronic applications, involving biosynthetic systems, photosynthetic systems, biophotovoltaic systems, and bioelectronic devices. The challenges and outlooks of WSCPs in designing high-performance bioelectronic systems are also discussed.
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Affiliation(s)
- Zenghao Wang
- Beijing National Laboratory for Molecular Sciences, Key Laboratory of Organic Solids, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China.
- College of Chemistry, University of Chinese Academy of Sciences, Beijing 100049, P. R. China
| | - Hongrui Lin
- Beijing National Laboratory for Molecular Sciences, Key Laboratory of Organic Solids, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China.
- College of Chemistry, University of Chinese Academy of Sciences, Beijing 100049, P. R. China
| | - Miaomiao Zhang
- Beijing National Laboratory for Molecular Sciences, Key Laboratory of Organic Solids, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China.
| | - Wen Yu
- Beijing National Laboratory for Molecular Sciences, Key Laboratory of Organic Solids, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China.
- College of Chemistry, University of Chinese Academy of Sciences, Beijing 100049, P. R. China
| | - Chuanwei Zhu
- Beijing National Laboratory for Molecular Sciences, Key Laboratory of Organic Solids, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China.
- College of Chemistry, University of Chinese Academy of Sciences, Beijing 100049, P. R. China
| | - Pengcheng Wang
- Beijing National Laboratory for Molecular Sciences, Key Laboratory of Organic Solids, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China.
| | - Yiming Huang
- Beijing National Laboratory for Molecular Sciences, Key Laboratory of Organic Solids, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China.
| | - Fengting Lv
- Beijing National Laboratory for Molecular Sciences, Key Laboratory of Organic Solids, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China.
| | - Haotian Bai
- Beijing National Laboratory for Molecular Sciences, Key Laboratory of Organic Solids, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China.
| | - Shu Wang
- Beijing National Laboratory for Molecular Sciences, Key Laboratory of Organic Solids, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China.
- College of Chemistry, University of Chinese Academy of Sciences, Beijing 100049, P. R. China
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16
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Liang Y, Qiao L, Qiao B, Guo B. Conductive hydrogels for tissue repair. Chem Sci 2023; 14:3091-3116. [PMID: 36970088 PMCID: PMC10034154 DOI: 10.1039/d3sc00145h] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Accepted: 02/20/2023] [Indexed: 02/23/2023] Open
Abstract
Conductive hydrogels (CHs) combine the biomimetic properties of hydrogels with the physiological and electrochemical properties of conductive materials, and have attracted extensive attention in the past few years. In addition, CHs have high conductivity and electrochemical redox properties and can be used to detect electrical signals generated in biological systems and conduct electrical stimulation to regulate the activities and functions of cells including cell migration, cell proliferation, and cell differentiation. These properties give CHs unique advantages in tissue repair. However, the current review of CHs is mostly focused on their applications as biosensors. Therefore, this article reviewed the new progress of CHs in tissue repair including nerve tissue regeneration, muscle tissue regeneration, skin tissue regeneration and bone tissue regeneration in the past five years. We first introduced the design and synthesis of different types of CHs such as carbon-based CHs, conductive polymer-based CHs, metal-based CHs, ionic CHs, and composite CHs, and the types and mechanisms of tissue repair promoted by CHs including anti-bacterial, antioxidant and anti-inflammatory properties, stimulus response and intelligent delivery, real-time monitoring, and promoted cell proliferation and tissue repair related pathway activation, which provides a useful reference for further preparation of bio-safer and more efficient CHs used in tissue regeneration.
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Affiliation(s)
- Yongping Liang
- State Key Laboratory for Mechanical Behavior of Materials, and Frontier Institute of Science and Technology, Xi'an Jiaotong University Xi'an 710049 China +86-29-83395131 +86-29-83395340
| | - Lipeng Qiao
- State Key Laboratory for Mechanical Behavior of Materials, and Frontier Institute of Science and Technology, Xi'an Jiaotong University Xi'an 710049 China +86-29-83395131 +86-29-83395340
| | - Bowen Qiao
- State Key Laboratory for Mechanical Behavior of Materials, and Frontier Institute of Science and Technology, Xi'an Jiaotong University Xi'an 710049 China +86-29-83395131 +86-29-83395340
| | - Baolin Guo
- State Key Laboratory for Mechanical Behavior of Materials, and Frontier Institute of Science and Technology, Xi'an Jiaotong University Xi'an 710049 China +86-29-83395131 +86-29-83395340
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University Xi'an 710049 China
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17
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Conductive and Adhesive Granular Alginate Hydrogels for On-Tissue Writable Bioelectronics. Gels 2023; 9:gels9020167. [PMID: 36826337 PMCID: PMC9957464 DOI: 10.3390/gels9020167] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 02/15/2023] [Accepted: 02/18/2023] [Indexed: 02/22/2023] Open
Abstract
Conductive hydrogels are promising materials in bioelectronics that ensure a tissue-like soft modulus and re-enact the electrophysiological function of damaged tissues. However, recent approaches to fabricating conductive hydrogels have proved difficult: fixing of the conductive hydrogels on the target tissues hydrogels requires the aids from other medical glues because of their weak tissue-adhesiveness. In this study, an intrinsically conductive and tissue-adhesive granular hydrogel consisting of a PEDOT:PSS conducting polymer and an adhesive catechol-conjugated alginate polymer was fabricated via an electrohydrodynamic spraying method. Because alginate-based polymers can be crosslinked by calcium ions, alginate-catechol polymers mixed with PEDOT:PSS granular hydrogels (ACP) were easily fabricated. The fabricated ACP exhibited not only adhesive and shear-thinning properties but also conductivity similar to that of muscle tissue. Additionally, the granular structure makes the hydrogel injectable through a syringe, enabling on-tissue printing. This multifunctional granular hydrogel can be applied to soft and flexible electronics to connect humans and machines.
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18
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RANDHAWA AAYUSHI, DEB DUTTA SAYAN, GANGULY KEYA, V. PATIL TEJAL, LUTHFIKASARI RACHMI, LIM KITAEK. Understanding cell-extracellular matrix interactions for topology-guided tissue regeneration. BIOCELL 2023. [DOI: 10.32604/biocell.2023.026217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/11/2023]
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19
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Shin S, Hyun J. Matrix-Assisted In Situ Polymerization of a 3D Conductive Hydrogel Structure. ACS APPLIED MATERIALS & INTERFACES 2022; 14:52516-52523. [PMID: 36354752 DOI: 10.1021/acsami.2c15603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
It is challenging to fabricate 3D architectures of conductive hydrogels and impart uniform conductivity at the same time. Here, we demonstrate a one-step 3D printing technique for controlling the 3D structure of hydrogel materials while simultaneously conferring uniform conductivity. The core technology lies in the in situ polymerization of conductive polymers by the diffusion of monomers and redox initiators to an interface. An alginate ink containing ammonium peroxide as a redox initiator is printed in a silica nanoparticle matrix containing a pyrrole monomer. A 3D structure of conductive polypyrrole is uniformly fabricated on the surface of the alginate immediately after the printing. This simple process provides uniform electrical conductivity throughout the bulk structure.
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Affiliation(s)
- Sungchul Shin
- Department of Agriculture, Forestry and Bioresources, Seoul National University, Seoul08826, Republic of Korea
| | - Jinho Hyun
- Department of Agriculture, Forestry and Bioresources, Seoul National University, Seoul08826, Republic of Korea
- Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul08826, Republic of Korea
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20
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Ma Y, Wang X, Su T, Lu F, Chang Q, Gao J. Recent Advances in Macroporous Hydrogels for Cell Behavior and Tissue Engineering. Gels 2022; 8:606. [PMID: 36286107 PMCID: PMC9601978 DOI: 10.3390/gels8100606] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 09/07/2022] [Accepted: 09/14/2022] [Indexed: 11/23/2022] Open
Abstract
Hydrogels have been extensively used as scaffolds in tissue engineering for cell adhesion, proliferation, migration, and differentiation because of their high-water content and biocompatibility similarity to the extracellular matrix. However, submicron or nanosized pore networks within hydrogels severely limit cell survival and tissue regeneration. In recent years, the application of macroporous hydrogels in tissue engineering has received considerable attention. The macroporous structure not only facilitates nutrient transportation and metabolite discharge but also provides more space for cell behavior and tissue formation. Several strategies for creating and functionalizing macroporous hydrogels have been reported. This review began with an overview of the advantages and challenges of macroporous hydrogels in the regulation of cellular behavior. In addition, advanced methods for the preparation of macroporous hydrogels to modulate cellular behavior were discussed. Finally, future research in related fields was discussed.
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Affiliation(s)
| | | | | | | | - Qiang Chang
- Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, 1838 Guangzhou North Road, Guangzhou 510515, China
| | - Jianhua Gao
- Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, 1838 Guangzhou North Road, Guangzhou 510515, China
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21
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Muir VG, Qazi TH, Weintraub S, Torres Maldonado BO, Arratia PE, Burdick JA. Sticking Together: Injectable Granular Hydrogels with Increased Functionality via Dynamic Covalent Inter-Particle Crosslinking. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2022; 18:e2201115. [PMID: 35315233 PMCID: PMC9463088 DOI: 10.1002/smll.202201115] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Revised: 03/03/2022] [Indexed: 05/14/2023]
Abstract
Granular hydrogels are an exciting class of microporous and injectable biomaterials that are being explored for many biomedical applications, including regenerative medicine, 3D printing, and drug delivery. Granular hydrogels often possess low mechanical moduli and lack structural integrity due to weak physical interactions between microgels. This has been addressed through covalent inter-particle crosslinking; however, covalent crosslinking often occurs through temporal enzymatic methods or photoinitiated reactions, which may limit injectability and material processing. To address this, a hyaluronic acid (HA) granular hydrogel is developed with dynamic covalent (hydrazone) inter-particle crosslinks. Extrusion fragmentation is used to fabricate microgels from photocrosslinkable norbornene-modified HA, additionally modified with either aldehyde or hydrazide groups. Aldehyde and hydrazide-containing microgels are mixed and jammed to form adhesive granular hydrogels. These granular hydrogels possess enhanced mechanical integrity and shape stability over controls due to the covalent inter-particle bonds, while maintaining injectability due to the dynamic hydrazone bonds. The adhesive granular hydrogels are applied to 3D printing, which allows the printing of structures that are stable without any further post-processing. Additionally, the authors demonstrate that adhesive granular hydrogels allow for cell invasion in vitro. Overall, this work demonstrates the use of dynamic covalent inter-particle crosslinking to enhance injectable granular hydrogels.
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Affiliation(s)
- Victoria G Muir
- Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Taimoor H Qazi
- Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Shoshana Weintraub
- Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Bryan O Torres Maldonado
- Department of Mechanical Engineering and Applied Mechanics, University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Paulo E Arratia
- Department of Mechanical Engineering and Applied Mechanics, University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Jason A Burdick
- Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, 19104, USA
- BioFrontiers Institute, University of Colorado Boulder, Boulder, CO, 80303, USA
- Department of Chemical and Biological Engineering, College of Engineering and Applied Science, University of Colorado Boulder, Boulder, CO, 80303, USA
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22
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Muir VG, Prendergast ME, Burdick JA. Fragmenting Bulk Hydrogels and Processing into Granular Hydrogels for Biomedical Applications. J Vis Exp 2022:10.3791/63867. [PMID: 35662235 PMCID: PMC11022187 DOI: 10.3791/63867] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/07/2024] Open
Abstract
Granular hydrogels are jammed assemblies of hydrogel microparticles (i.e., "microgels"). In the field of biomaterials, granular hydrogels have many advantageous properties, including injectability, microscale porosity, and tunability by mixing multiple microgel populations. Methods to fabricate microgels often rely on water-in-oil emulsions (e.g., microfluidics, batch emulsions, electrospraying) or photolithography, which may present high demands in terms of resources and costs, and may not be compatible with many hydrogels. This work details simple yet highly effective methods to fabricate microgels using extrusion fragmentation and to process them into granular hydrogels useful for biomedical applications (e.g., 3D printing inks). First, bulk hydrogels (using photocrosslinkable hyaluronic acid (HA) as an example) are extruded through a series of needles with sequentially smaller diameters to form fragmented microgels. This microgel fabrication technique is rapid, low-cost, and highly scalable. Methods to jam microgels into granular hydrogels by centrifugation and vacuum-driven filtration are described, with optional post-crosslinking for hydrogel stabilization. Lastly, granular hydrogels fabricated from fragmented microgels are demonstrated as extrusion printing inks. While the examples described herein use photocrosslinkable HA for 3D printing, the methods are easily adaptable for a wide variety of hydrogel types and biomedical applications.
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Affiliation(s)
- Victoria G Muir
- Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania
| | - Margaret E Prendergast
- Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania
| | - Jason A Burdick
- Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania; BioFrontiers Institute, University of Colorado Boulder; Department of Chemical and Biological Engineering, College of Engineering and Applied Science, University of Colorado Boulder;
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23
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Danielsen SPO, Thompson BJ, Fredrickson GH, Nguyen TQ, Bazan GC, Segalman RA. Ionic Tunability of Conjugated Polyelectrolyte Solutions. Macromolecules 2022. [DOI: 10.1021/acs.macromol.2c00178] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- Scott P. O. Danielsen
- Department of Chemical Engineering, University of California, Santa Barbara, California 93106, United States
- Materials Research Laboratory, University of California, Santa Barbara, California 93106, United States
| | - Brittany J. Thompson
- Materials Research Laboratory, University of California, Santa Barbara, California 93106, United States
- School of Polymer Science and Engineering, University of Southern Mississippi, Hattiesburg, Mississippi 39406, United States
| | - Glenn H. Fredrickson
- Department of Chemical Engineering, University of California, Santa Barbara, California 93106, United States
- Materials Research Laboratory, University of California, Santa Barbara, California 93106, United States
- Materials Department, University of California, Santa Barbara, California 93106, United States
| | - Thuc-Quyen Nguyen
- Materials Research Laboratory, University of California, Santa Barbara, California 93106, United States
- Center for Polymers and Organic Solids, Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106, United States
| | - Guillermo C. Bazan
- Materials Research Laboratory, University of California, Santa Barbara, California 93106, United States
- Materials Department, University of California, Santa Barbara, California 93106, United States
- Center for Polymers and Organic Solids, Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106, United States
| | - Rachel A. Segalman
- Department of Chemical Engineering, University of California, Santa Barbara, California 93106, United States
- Materials Research Laboratory, University of California, Santa Barbara, California 93106, United States
- Materials Department, University of California, Santa Barbara, California 93106, United States
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24
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Wang J, Li Q, Li K, Sun X, Wang Y, Zhuang T, Yan J, Wang H. Ultra-High Electrical Conductivity in Filler-Free Polymeric Hydrogels Toward Thermoelectrics and Electromagnetic Interference Shielding. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2022; 34:e2109904. [PMID: 35064696 DOI: 10.1002/adma.202109904] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 01/19/2022] [Indexed: 06/14/2023]
Abstract
Conducting hydrogels have attracted much attention for the emerging field of hydrogel bioelectronics, especially poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) (PEDOT:PSS) based hydrogels, because of their great biocompatibility and stability. However, the electrical conductivities of hydrogels are often lower than 1 S cm-1 which are not suitable for digital circuits or applications in bioelectronics. Introducing conductive inorganic fillers into the hydrogels can improve their electrical conductivities. However, it may lead to compromises in compliance, biocompatibility, deformability, biodegradability, etc. Herein, a series of highly conductive ionic liquid (IL) doped PEDOT:PSS hydrogels without any conductive fillers is reported. These hydrogels exhibit high conductivities up to ≈305 S cm-1 , which is ≈8 times higher than the record of polymeric hydrogels without conductive fillers in literature. The high electrical conductivity results in enhanced areal thermoelectric output power for hydrogel-based thermoelectric devices, and high specific electromagnetic interference (EMI) shielding efficiency which is about an order in magnitude higher than that of state-of-the-art conductive hydrogels in literature. Furthermore, these stretchable (strain >30%) hydrogels exhibit fast self-healing, and shape/size-tunable properties, which are desirable for hydrogel bioelectronics and wearable organic devices. The results indicate that these highly conductive hydrogels are promising in applications such as sensing, thermoelectrics, EMI shielding, etc.
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Affiliation(s)
- Jing Wang
- Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710054, China
| | - Qing Li
- Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710054, China
| | - Kuncai Li
- Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710054, China
| | - Xu Sun
- Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710054, China
| | - Yizhuo Wang
- Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710054, China
| | - Tiantian Zhuang
- Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710054, China
| | - Junjie Yan
- State Key Laboratory of Multiphase Flow in Power Engineering, Xi'an Jiaotong University, Xi'an, 710054, China
- School of energy and power engineering, Xi'an Jiaotong University, Xi'an, 710054, China
| | - Hong Wang
- Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710054, China
- State Key Laboratory of Multiphase Flow in Power Engineering, Xi'an Jiaotong University, Xi'an, 710054, China
- School of energy and power engineering, Xi'an Jiaotong University, Xi'an, 710054, China
- Zhejiang YunFeng New Materials Technology Co., Ltd, No. 755 Hongji Street, Jinghua Zhejiang, 321015, China
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25
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Zhou N, Ma L. Smart bioelectronics and biomedical devices. Biodes Manuf 2022; 5:1-5. [PMID: 35043079 PMCID: PMC8759059 DOI: 10.1007/s42242-021-00179-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 11/22/2021] [Indexed: 12/26/2022]
Affiliation(s)
- Nanjia Zhou
- Key Laboratory of 3D Micro/Nano Fabrication and Characterization of Zhejiang Province, School of Engineering, Westlake University, Hangzhou, 310024 China
- Institute of Advanced Technology, Westlake Institute for Advanced Study, Hangzhou, 310024 China
| | - Liang Ma
- State Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University, Hangzhou, 310058 China
- School of Mechanical Engineering, Zhejiang University, Hangzhou, 310058 China
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26
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Micro-scaffolds as synthetic cell niches: recent advances and challenges. Curr Opin Biotechnol 2021; 73:290-299. [PMID: 34619481 DOI: 10.1016/j.copbio.2021.08.016] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 08/19/2021] [Accepted: 08/21/2021] [Indexed: 01/01/2023]
Abstract
Micro-fabrication and nano-fabrication provide useful approaches to address fundamental biological questions by mimicking the physiological microenvironment in which cells carry out their functions. In particular, 2D patterns and 3D scaffolds obtained via lithography, direct laser writing, and other techniques allow for shaping hydrogels, synthetic polymers and biologically derived materials to create structures for (single) cell culture. Applications of micro-scaffolds mimicking cell niches include stem cell self-renewal, differentiation, and lineage specification. This review moves from technological aspects of scaffold microfabrication for cell biological applications to a broad overview of advances in (stem) cell research: achievements for embryonic, induced pluripotent, mesenchymal, and neural stem cells are treated in detail, while a particular section is dedicated to micro-scaffolds used to study single cells in basic cell biology.
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27
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Roth JG, Huang MS, Li TL, Feig VR, Jiang Y, Cui B, Greely HT, Bao Z, Paşca SP, Heilshorn SC. Advancing models of neural development with biomaterials. Nat Rev Neurosci 2021; 22:593-615. [PMID: 34376834 PMCID: PMC8612873 DOI: 10.1038/s41583-021-00496-y] [Citation(s) in RCA: 64] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/25/2021] [Indexed: 12/12/2022]
Abstract
Human pluripotent stem cells have emerged as a promising in vitro model system for studying the brain. Two-dimensional and three-dimensional cell culture paradigms have provided valuable insights into the pathogenesis of neuropsychiatric disorders, but they remain limited in their capacity to model certain features of human neural development. Specifically, current models do not efficiently incorporate extracellular matrix-derived biochemical and biophysical cues, facilitate multicellular spatio-temporal patterning, or achieve advanced functional maturation. Engineered biomaterials have the capacity to create increasingly biomimetic neural microenvironments, yet further refinement is needed before these approaches are widely implemented. This Review therefore highlights how continued progression and increased integration of engineered biomaterials may be well poised to address intractable challenges in recapitulating human neural development.
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Affiliation(s)
- Julien G Roth
- Institute for Stem Cell Biology & Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Michelle S Huang
- Department of Chemical Engineering, Stanford University, Stanford, CA, USA
| | - Thomas L Li
- Department of Chemistry, Stanford University, Stanford, CA, USA
- Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA
| | - Vivian R Feig
- Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA
| | - Yuanwen Jiang
- Department of Chemical Engineering, Stanford University, Stanford, CA, USA
| | - Bianxiao Cui
- Department of Chemistry, Stanford University, Stanford, CA, USA
| | - Henry T Greely
- Stanford Law School, Stanford University, Stanford, CA, USA
| | - Zhenan Bao
- Department of Chemical Engineering, Stanford University, Stanford, CA, USA
| | - Sergiu P Paşca
- Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA
| | - Sarah C Heilshorn
- Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA.
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