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1
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Reinehr P, Diel LF, Diz FM, Balbinot GDS, Monteiro WF, Ligabue RA, Lamers ML, Kunrath MF. Three-dimensional bioactive collagen scaffolds incorporated with titanate nanotubes for tissue regeneration. Colloids Surf B Biointerfaces 2025; 252:114638. [PMID: 40157167 DOI: 10.1016/j.colsurfb.2025.114638] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2025] [Revised: 03/07/2025] [Accepted: 03/15/2025] [Indexed: 04/01/2025]
Abstract
The development of three-dimensional (3D) biomimetic scaffolds for bone and soft tissue engineering has received increasing attention due to their ability to mimic the extracellular matrix (ECM) environment. This study presents the development and characterization of a 3D collagen matrix incorporating titanate nanotubes (TNT) aiming to improve cell migration and biocompatibility, with potential applications in bioink for bone and soft tissue regeneration. TNT were hydrothermally synthesized, and their properties were characterized using materials analysis techniques. After the incorporation of human fibroblasts into the collagen matrices with or without TNT, biological characterization was performed. The results showed that the incorporation of TNT significantly improved the migration efficiency and directionality compared to collagen-only matrices, which were more evident after long-term incubation. This indicates that the addition of TNT to the collagen matrixes improves the mechanical properties, promotes biocompatibility, and induces a superior environment for cell migration. These findings contribute to the development of new biomaterials for tissue engineering and demonstrate the potential of TNT as a key component of bioengineered biomaterials for bone and soft tissue regeneration.
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Affiliation(s)
- Petra Reinehr
- Postgraduate Program in Physiology, Institute of Basic Health Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil
| | - Leonardo Francisco Diel
- Basic Research Center in Dentistry, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Fernando Mendonça Diz
- Preclinical Research Center, Brain Institute of Rio Grande do Sul, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, Brazil
| | - Gabriela de Souza Balbinot
- Dental Materials Laboratory, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Wesley Formentin Monteiro
- Laboratory of Reactivity and Catalysis, Federal University of Rio de Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil
| | - Rosane Angélica Ligabue
- Graduate Program in Materials Engineering and Technology, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, Brazil
| | - Marcelo Lazzaron Lamers
- Basic Research Center in Dentistry, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil; Department of Morphological Sciences, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Marcel Ferreira Kunrath
- School of Health and Life Sciences, Postgraduate Program in Dentistry, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil; Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
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2
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Cen C, Zhang Y, Cao Y, Hu C, Tang L, Liu C, Wang T, Peng W. Construction of a 3D Degradable PLLA/β-TCP/CS Scaffold for Establishing an Induced Membrane Inspired by the Modified Single-Stage Masquelet Technique. ACS Biomater Sci Eng 2025; 11:1629-1645. [PMID: 39943835 PMCID: PMC11900768 DOI: 10.1021/acsbiomaterials.4c01849] [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: 10/04/2024] [Revised: 02/05/2025] [Accepted: 02/05/2025] [Indexed: 03/11/2025]
Abstract
Although the Masquelet-induced membrane technique (MIMT) is now employed worldwide for bone defects, it often needs to be repeated and autogenous bone graft. This study aims to investigate the theoretical feasibility of replacing PMMA (poly(methyl methacrylate)) bone cement with PLLA (poly-l-lactic acid)/β -TCP (beta-tricalcium phosphate)/CS (calcium sulfate) scaffold for single-stage bone defect reconstruction, which evoke the induced membrane (IM) formation in the early stage and directly acts as the implantation in the second stage to reconstruct the bone defect. We constructed a corn-like PLLA/β -TCP/CS scaffold by the fused deposition 3D printing method. The characterizations of the scaffolds were investigated systematically. The P/T15/S15 scaffolds (the PLLA/β -TCP/CS scaffold with a 15% mass fraction of β-TCP and 15% mass fraction of CS) were filled into the large-segmental radius bone defects of white rabbits to evoke the formation of IMs. HE (hematoxylin-eosin) and VG (van gieson) staining, along with immunofluorescent staining, were performed to analyze the architecture and cellularity, the expression of BMP-2 (bone morphogenetic protein-2), VEGF (vascular endothelial growth factor), and TGF-β1 (transforming growth factor-β1) was evaluated by IHC (immunohistochemistry) and WB (western-blot) respectively, the ALP (alkaline phosphatase) and ARS (alizarin red S) staining was applied to assess the osteogenic potential. The corn-like PLLA/β-TCP/CS scaffolds with excellent physicochemical properties are successfully constructed using the fused deposition 3D printing technique. The HE and VG staining, along with immunofluorescent staining, suggested that the P/T15/S15 scaffold effectively mediated the formation of IM after 6 weeks of placement. A significant presence of M2 macrophages was observed in IM. The results of IHC and WB demonstrated that the IMs derived from the P/T15/S15 scaffolds exhibited elevated levels of VEGF, BMP-2, and TGF-β1, all of which promote the osteogenic differentiation of BMSCs. The results of cellular immunofluorescence, flow cytometry, and WB indicate that P/T15/S15 regulates the phenotypic polarization of M0 macrophages toward the M2 phenotype via the PI3K/AKT/β-Catenin pathway. These findings suggest that the biodegradable PLLA/β-TCP/CS scaffold may serve as a viable alternative to PMMA bone cement for single-stage bone defect reconstruction, owing to its unique ability to stimulate IM formation and promote the polarization of macrophages toward the M2 phenotype. This work presents innovative materials and strategies for the management of bone defects.
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Affiliation(s)
- Chaode Cen
- School
of Clinical Medicine, The Guizhou Medical
University, Guiyang 550025,China
- Department
of Orthopedics, The Beijing Jishuitan Hospital
Guizhou Hospital, Guiyang 550014, China
| | - Yong Zhang
- Department
of gynaecology and obstetrics, Guiyang First
People’s Hospital, Guiyang 550005, China
| | - Yongfei Cao
- Department
of Orthopedics, The Beijing Jishuitan Hospital
Guizhou Hospital, Guiyang 550014, China
| | - Chaoran Hu
- Department
of Orthopedics, The Beijing Jishuitan Hospital
Guizhou Hospital, Guiyang 550014, China
| | - Lingli Tang
- Department
of Orthopedics, The Beijing Jishuitan Hospital
Guizhou Hospital, Guiyang 550014, China
| | - Chengwei Liu
- Department
of Orthopedics, The Beijing Jishuitan Hospital
Guizhou Hospital, Guiyang 550014, China
| | - Tao Wang
- School
of Clinical Medicine, The Guizhou Medical
University, Guiyang 550025,China
- Department
of Emergency Surgery, The Affiliated Hospital
of Guizhou Medical University, Guiyang, Guizhou 550004, China
| | - Wuxun Peng
- School
of Clinical Medicine, The Guizhou Medical
University, Guiyang 550025,China
- Department
of Emergency Surgery, The Affiliated Hospital
of Guizhou Medical University, Guiyang, Guizhou 550004, China
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3
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Li S, Huang C, Liu H, Han X, Wang Z, Chen Z, Huang J, Wang Z. A viscoelastic-stochastic model of cell adhesion considering matrix morphology and medium viscoelasticity. SOFT MATTER 2024; 20:7270-7283. [PMID: 39239672 DOI: 10.1039/d4sm00740a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/07/2024]
Abstract
Quantitative investigation of the adhesive behavior between cells and the extracellular matrix (ECM) through molecular bonds is essential for cell culture and bio-medical engineering in vitro. Cell adhesion is a complex multi-scale behavior that includes temporal and spatial scales. However, the influence of the cell and matrix creep effect and the complex spatial morphology characteristics of the matrix on the cell adhesion mechanism is unclear. In the present study, an idealized theoretical model has been considered, where the adhesion of cells and the matrix is simplified into a planar strain problem of homogeneous viscoelastic half-spaces. Furthermore, a new viscoelastic-stochastic model that considers the morphological characteristics of the matrix, the viscoelasticity of the cell and the viscoelasticity of the substrate was developed under the action of a constant external force. The model characterizes the matrix topographical features by fractal dimension (FD), interprets the effects of FD and medium viscoelasticity on the molecular bond force and the receptor-ligand bond re-association rate and reveals a new mechanism for the stable adhesion of molecular bond clusters by Monte Carlo simulation. Based on this model, it was identified that the temporal and spatial distribution of molecular bond force was affected by the matrix FD and the lifetime and stability of the molecular bond cluster could be significantly improved by tuning the FD. At the same time, the viscoelastic creep effect of the cell and matrix increased the re-association rate of open bonds and could expand the window of stable adhesion more flexibly.
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Affiliation(s)
- Shuying Li
- Centre for Advanced Jet Engineering Technology (CaJET), Key Laboratory of High-efficiency and Clean Mechanical Manufacture (Ministry of Education), National Experimental Teaching Demonstration Center for Mechanical Engineering (Shandong University), School of Mechanical Engineering, Shandong University, Jinan 250061, China.
| | - Chuanzhen Huang
- School of Mechanical Engineering, Yanshan University, Qinhuangdao 066004, China.
| | - Hanlian Liu
- Centre for Advanced Jet Engineering Technology (CaJET), Key Laboratory of High-efficiency and Clean Mechanical Manufacture (Ministry of Education), National Experimental Teaching Demonstration Center for Mechanical Engineering (Shandong University), School of Mechanical Engineering, Shandong University, Jinan 250061, China.
| | - Xu Han
- Centre for Advanced Jet Engineering Technology (CaJET), Key Laboratory of High-efficiency and Clean Mechanical Manufacture (Ministry of Education), National Experimental Teaching Demonstration Center for Mechanical Engineering (Shandong University), School of Mechanical Engineering, Shandong University, Jinan 250061, China.
| | - Zhichao Wang
- Centre for Advanced Jet Engineering Technology (CaJET), Key Laboratory of High-efficiency and Clean Mechanical Manufacture (Ministry of Education), National Experimental Teaching Demonstration Center for Mechanical Engineering (Shandong University), School of Mechanical Engineering, Shandong University, Jinan 250061, China.
| | - Zhuang Chen
- Centre for Advanced Jet Engineering Technology (CaJET), Key Laboratory of High-efficiency and Clean Mechanical Manufacture (Ministry of Education), National Experimental Teaching Demonstration Center for Mechanical Engineering (Shandong University), School of Mechanical Engineering, Shandong University, Jinan 250061, China.
| | - Jun Huang
- Centre for Advanced Jet Engineering Technology (CaJET), Key Laboratory of High-efficiency and Clean Mechanical Manufacture (Ministry of Education), National Experimental Teaching Demonstration Center for Mechanical Engineering (Shandong University), School of Mechanical Engineering, Shandong University, Jinan 250061, China.
| | - Zhen Wang
- School of Mechanical Engineering, Yanshan University, Qinhuangdao 066004, China.
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Diez-Escudero A, Espanol M, Ginebra MP. High-aspect-ratio nanostructured hydroxyapatite: towards new functionalities for a classical material. Chem Sci 2023; 15:55-76. [PMID: 38131070 PMCID: PMC10732134 DOI: 10.1039/d3sc05344j] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Accepted: 11/20/2023] [Indexed: 12/23/2023] Open
Abstract
Hydroxyapatite-based materials have been widely used in countless applications, such as bone regeneration, catalysis, air and water purification or protein separation. Recently, much interest has been given to controlling the aspect ratio of hydroxyapatite crystals from bulk samples. The ability to exert control over the aspect ratio may revolutionize the applications of these materials towards new functional materials. Controlling the shape, size and orientation of HA crystals allows obtaining high aspect ratio structures, improving several key properties of HA materials such as molecule adsorption, ion exchange, catalytic reactions, and even overcoming the well-known brittleness of ceramic materials. Regulating the morphogenesis of HA crystals to form elongated oriented fibres has led to flexible inorganic synthetic sponges, aerogels, membranes, papers, among others, with applications in sustainability, energy and catalysis, and especially in the biomedical field.
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Affiliation(s)
- Anna Diez-Escudero
- Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Universitat Politècnica de Catalunya (UPC) Av. Eduard Maristany 16 08019 Barcelona Spain
- Barcelona Research Center in Multiscale Science and Engineering, Universitat Politècnica de Catalunya (UPC) Av. Eduard Maristany 16 08019 Barcelona Spain
| | - Montserrat Espanol
- Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Universitat Politècnica de Catalunya (UPC) Av. Eduard Maristany 16 08019 Barcelona Spain
- Barcelona Research Center in Multiscale Science and Engineering, Universitat Politècnica de Catalunya (UPC) Av. Eduard Maristany 16 08019 Barcelona Spain
| | - Maria-Pau Ginebra
- Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Universitat Politècnica de Catalunya (UPC) Av. Eduard Maristany 16 08019 Barcelona Spain
- Barcelona Research Center in Multiscale Science and Engineering, Universitat Politècnica de Catalunya (UPC) Av. Eduard Maristany 16 08019 Barcelona Spain
- Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology Baldiri Reixac 10-12 08028 Barcelona Spain
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5
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Majidi M, Pakzad S, Salimi M, Azadbakht A, Hajighasemlou S, Amoupour M, Nokhbedehghan Z, Bonakdar S, Sineh Sepehr K, Pal Singh Chauhan N, Gholipourmalekabadi M. Macrophage cell morphology-imprinted substrates can modulate mesenchymal stem cell behaviors and macrophage M1/M2 polarization for wound healing applications. Biotechnol Bioeng 2023; 120:3638-3654. [PMID: 37668186 DOI: 10.1002/bit.28546] [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: 03/15/2023] [Revised: 08/09/2023] [Accepted: 08/24/2023] [Indexed: 09/06/2023]
Abstract
Mesenchymal stem cells and macrophages (MQ) are two very important cells involved in the normal wound healing process. It is well understood that topological cues and mechanical factors can lead to different responses in stem cells and MQ by influencing their shape, cytoskeleton proliferation, migration, and differentiation, which play an essential role in the success or failure of biomaterial implantation and more importantly wound healing. On the other hand, the polarization of MQ from proinflammatory (M1) to prohealing (M2) phenotypes has a critical role in the acceleration of wound healing. In this study, the morphology of different MQ subtypes (M0, M1, and M2) was imprinted on a silicon surface (polydimethylsiloxane [PDMS]) to prepare a nano-topography cell-imprinted substrate with the ability to induce anti-inflammatory effects on the mouse adipose-derived stem cells (ADSCs) and RAW264.7 monocyte cell line (MO). The gene expression profiles and flow cytometry of MQ revealed that the cell shape microstructure promoted the MQ phenotypes according to the specific shape of each pattern. The ELISA results were in agreement with the gene expression profiles. The ADSCs on the patterned PDMS exhibited remarkably different shapes from no-patterned PDMS. The MOs grown on M2 morphological patterns showed a significant increase in expression and section of anti-inflammatory cytokine compared with M0 and M1 patterns. The ADSCs homing in niches heavily deformed the cytoskeletal, which is probably why the gene expression and phenotype unexpectedly changed. In conclusion, wound dressings with M2 cell morphology-induced surfaces are suggested as excellent anti-inflammatory and antiscarring dressings.
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Affiliation(s)
- Mohammad Majidi
- Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Saeedreza Pakzad
- Food and Drug Laboratory Research Center, Food and Drug Administration, Iran Ministry of Health and Medical Education, Tehran, Iran
| | - Maryam Salimi
- Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abdolnaser Azadbakht
- Department of Biomedical Engineering, Central Tehran Branch, Islamic Azad University, Tehran, Iran
- Stem Cell Research Center, Tissue Engineering and Regenerative Medicine Institute, Central Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Saieh Hajighasemlou
- Food and Drug Administration, Iran Ministry of Health and Medical Education, Tehran, Iran
| | - Moein Amoupour
- Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Zeinab Nokhbedehghan
- Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
| | | | - Koushan Sineh Sepehr
- Laboratory Sciences Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | | | - Mazaher Gholipourmalekabadi
- Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
- Cellular and Molecular Research Centre, Iran University of Medical Sciences, Tehran, Iran
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6
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Jesus D, Pinho AR, Gomes MC, Oliveira CS, Mano JF. Emerging modulators for osteogenic differentiation: a combination of chemical and topographical cues for bone microenvironment engineering. SOFT MATTER 2022; 18:3107-3119. [PMID: 35373803 DOI: 10.1039/d2sm00009a] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Bone presents an intrinsic ability for self-regeneration and repair, however critical defects and large fractures require invasive and time-consuming clinical interventions. As an alternative to current therapy, bone tissue engineering (BTE) has primarily aimed to recreate the bone microenvironment by delivering key biomolecules and/or by modification of scaffolds to guide cell fate towards the osteogenic lineage or other phenotypes that may benefit the bone regeneration mechanism. Considering that bone cells communicate, in their native microenvironment, through biochemical and physical signals, most strategies fail when considering only chemical, geometrical or mechanical cues. This is not representative of the physiological conditions, where the cells are simultaneously in contact and stimulated by several cues. Therefore, this review explores the synergistic effect of biochemical/physical cues in regulating cellular events, namely cell adhesion, proliferation, osteogenic differentiation, and mineralization, highlighting the importance of the combined modifications for the development of innovative bone regenerative therapies.
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Affiliation(s)
- Diana Jesus
- Department of Chemistry, CICECO - Aveiro Institute of Materials, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.
| | - Ana R Pinho
- Department of Chemistry, CICECO - Aveiro Institute of Materials, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.
| | - Maria C Gomes
- Department of Chemistry, CICECO - Aveiro Institute of Materials, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.
| | - Cláudia S Oliveira
- Department of Chemistry, CICECO - Aveiro Institute of Materials, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.
| | - João F Mano
- Department of Chemistry, CICECO - Aveiro Institute of Materials, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.
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7
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Carthew J, Taylor JBJ, Garcia-Cruz MR, Kiaie N, Voelcker NH, Cadarso VJ, Frith JE. The Bumpy Road to Stem Cell Therapies: Rational Design of Surface Topographies to Dictate Stem Cell Mechanotransduction and Fate. ACS APPLIED MATERIALS & INTERFACES 2022; 14:23066-23101. [PMID: 35192344 DOI: 10.1021/acsami.1c22109] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Cells sense and respond to a variety of physical cues from their surrounding microenvironment, and these are interpreted through mechanotransductive processes to inform their behavior. These mechanisms have particular relevance to stem cells, where control of stem cell proliferation, potency, and differentiation is key to their successful application in regenerative medicine. It is increasingly recognized that surface micro- and nanotopographies influence stem cell behavior and may represent a powerful tool with which to direct the morphology and fate of stem cells. Current progress toward this goal has been driven by combined advances in fabrication technologies and cell biology. Here, the capacity to generate precisely defined micro- and nanoscale topographies has facilitated the studies that provide knowledge of the mechanotransducive processes that govern the cellular response as well as knowledge of the specific features that can drive cells toward a defined differentiation outcome. However, the path forward is not fully defined, and the "bumpy road" that lays ahead must be crossed before the full potential of these approaches can be fully exploited. This review focuses on the challenges and opportunities in applying micro- and nanotopographies to dictate stem cell fate for regenerative medicine. Here, key techniques used to produce topographic features are reviewed, such as photolithography, block copolymer lithography, electron beam lithography, nanoimprint lithography, soft lithography, scanning probe lithography, colloidal lithography, electrospinning, and surface roughening, alongside their advantages and disadvantages. The biological impacts of surface topographies are then discussed, including the current understanding of the mechanotransductive mechanisms by which these cues are interpreted by the cells, as well as the specific effects of surface topographies on cell differentiation and fate. Finally, considerations in translating these technologies and their future prospects are evaluated.
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Affiliation(s)
- James Carthew
- Materials Science and Engineering, Monash University, Clayton, Victoria 3800, Australia
| | - Jason B J Taylor
- Mechanical and Aerospace Engineering, Monash University, Clayton, Victoria 3800, Australia
| | - Maria R Garcia-Cruz
- Materials Science and Engineering, Monash University, Clayton, Victoria 3800, Australia
| | - Nasim Kiaie
- Materials Science and Engineering, Monash University, Clayton, Victoria 3800, Australia
| | - Nicolas H Voelcker
- Materials Science and Engineering, Monash University, Clayton, Victoria 3800, Australia
- Melbourne Centre for Nanofabrication, Victorian Node of the Australian National Fabrication Facility, Clayton, Victoria 3168, Australia
- Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia
- ARC Centre for Cell and Tissue Engineering Technologies, Monash University, Clayton, Victoria 3800, Australia
- CSIRO Manufacturing, Bayview Avenue, Clayton, VIC 3168, Australia
| | - Victor J Cadarso
- Mechanical and Aerospace Engineering, Monash University, Clayton, Victoria 3800, Australia
- Centre to Impact Antimicrobial Resistance, Monash University, Clayton, Victoria 3800, Australia
| | - Jessica E Frith
- Materials Science and Engineering, Monash University, Clayton, Victoria 3800, Australia
- ARC Centre for Cell and Tissue Engineering Technologies, Monash University, Clayton, Victoria 3800, Australia
- Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria 3800, Australia
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8
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dos Anjos KFL, da Silva CDC, de Souza MAA, de Mattos AB, Coelho LCBB, Machado G, de Melo JV, de Figueiredo RCBQ. The Deposition of a Lectin from Oreochromis niloticus on the Surface of Titanium Dioxide Nanotubes Improved the Cell Adhesion, Proliferation, and Osteogenic Activity of Osteoblast-like Cells. Biomolecules 2021; 11:1748. [PMID: 34944393 PMCID: PMC8698878 DOI: 10.3390/biom11121748] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Revised: 09/13/2021] [Accepted: 09/16/2021] [Indexed: 12/20/2022] Open
Abstract
Titanium and its alloys are used as biomaterials for medical and dental applications, due to their mechanical and physical properties. Surface modifications of titanium with bioactive molecules can increase the osseointegration by improving the interface between the bone and implant. In this work, titanium dioxide nanotubes (TiO2NTs) were functionalized with a lectin from the plasma of the fish Oreochromis niloticus aiming to favor the adhesion and proliferation of osteoblast-like cells, improving its biocompatibility. The TiO2NTs were obtained by anodization of titanium and annealed at 400 °C for 3 h. The resulting TiO2NTs were characterized by high-resolution scanning electron microscopy. The successful incorporation of OniL on the surface of TiO2NTs, by spin coating, was demonstrated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIE), and attenuated total reflection-Fourier transform infrared spectrum (ATR-FTIR). Our results showed that TiO2NTs were successfully synthesized in a regular and well-distributed way. The modification of TiO2NTs with OniL favored adhesion, proliferation, and the osteogenic activity of osteoblast-like cells, suggesting its use to improve the quality and biocompatibility of titanium-based biomaterials.
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Affiliation(s)
- Keicyanne Fernanda Lessa dos Anjos
- Departamento de Microbiologia, Instituto Aggeu Magalhães (FIOCRUZ-PE), Campus da UFPE, Av. Prof. Moraes Rego s/n Cidade Universitária, Recife 50670-420, PE, Brazil; (K.F.L.d.A.); (C.D.C.d.S.); (M.A.A.d.S.)
| | - Cynarha Daysy Cardoso da Silva
- Departamento de Microbiologia, Instituto Aggeu Magalhães (FIOCRUZ-PE), Campus da UFPE, Av. Prof. Moraes Rego s/n Cidade Universitária, Recife 50670-420, PE, Brazil; (K.F.L.d.A.); (C.D.C.d.S.); (M.A.A.d.S.)
| | - Mary Angela Aranda de Souza
- Departamento de Microbiologia, Instituto Aggeu Magalhães (FIOCRUZ-PE), Campus da UFPE, Av. Prof. Moraes Rego s/n Cidade Universitária, Recife 50670-420, PE, Brazil; (K.F.L.d.A.); (C.D.C.d.S.); (M.A.A.d.S.)
| | - Alessandra Batista de Mattos
- Centro de Tecnologias Estratégicas do Nordeste (CETENE), Av. Prof. Luiz Freire, 01. Cidade Universitária, Recife 50740-540, PE, Brazil; (A.B.d.M.); (G.M.); (J.V.d.M.)
| | - Luana Cassandra Breitenbach Barroso Coelho
- Centro de Ciências Biológicas, Departamento de Bioquímica, Campus da UFPE, Universidade Federal de Pernambuco (UFPE), Av. Prof. Moraes Rego s/n Cidade Universitária, Recife 50670-420, PE, Brazil;
| | - Giovanna Machado
- Centro de Tecnologias Estratégicas do Nordeste (CETENE), Av. Prof. Luiz Freire, 01. Cidade Universitária, Recife 50740-540, PE, Brazil; (A.B.d.M.); (G.M.); (J.V.d.M.)
| | - Janaina Viana de Melo
- Centro de Tecnologias Estratégicas do Nordeste (CETENE), Av. Prof. Luiz Freire, 01. Cidade Universitária, Recife 50740-540, PE, Brazil; (A.B.d.M.); (G.M.); (J.V.d.M.)
| | - Regina Celia Bressan Queiroz de Figueiredo
- Departamento de Microbiologia, Instituto Aggeu Magalhães (FIOCRUZ-PE), Campus da UFPE, Av. Prof. Moraes Rego s/n Cidade Universitária, Recife 50670-420, PE, Brazil; (K.F.L.d.A.); (C.D.C.d.S.); (M.A.A.d.S.)
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9
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Shah V, Patel S, Shah J. Emerging Role of Piezo Ion Channels in Cardiovascular Development. Dev Dyn 2021; 251:276-286. [PMID: 34255896 DOI: 10.1002/dvdy.401] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 06/12/2021] [Accepted: 07/09/2021] [Indexed: 12/23/2022] Open
Abstract
Mechanical cues are crucial for vascular development and the proper differentiation of various cell types. Piezo1 and Piezo2 are mechanically activated cationic channels expressed in various cell types, especially in vascular smooth muscle and endothelial cells. It is present as a transmembrane homotrimeric complex, regulating calcium influx. Local blood flow associated shear stress, in addition to blood pressure associated cell membrane stretching are key Piezo channel activators. There is rising proof, showcasing Piezo channels significance in myocytes, cardiac fibroblast, vascular tone maintenance, atherosclerosis, hypertension, NO generation, and baroreceptor reflex. Here, we review the role of Piezo channels in cardiovascular development and its associated clinical disorders. Also, emphasizing on Piezo channel modulators which might lead to novel therapies for cardiovascular diseases. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Vandit Shah
- Department of Pharmacology, L.M. College of Pharmacy, Navrangpura, Ahmedabad, Gujarat, India
| | - Sandip Patel
- Department of Pharmacology, L.M. College of Pharmacy, Navrangpura, Ahmedabad, Gujarat, India
| | - Jigna Shah
- Department of Pharmacology, Institute of Pharmacy Nirma University, Ahmedabad, Gujarat, India
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10
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Sun Y, Wu Q, Zhang Y, Dai K, Wei Y. 3D-bioprinted gradient-structured scaffold generates anisotropic cartilage with vascularization by pore-size-dependent activation of HIF1α/FAK signaling axis. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2021; 37:102426. [PMID: 34175454 DOI: 10.1016/j.nano.2021.102426] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Revised: 05/06/2021] [Accepted: 06/01/2021] [Indexed: 02/06/2023]
Abstract
Articular cartilage injury is one of the most common diseases in orthopedics, which seriously affects patients' life quality, the development of a biomimetic scaffold that mimics the multi-layered gradient structure of native cartilage is a new cartilage repair strategy. It has been shown that scaffold topography affects cell attachment, proliferation, and differentiation; the underlying molecular mechanism of cell-scaffold interaction is still unclear. In the present study, we construct an anisotropic gradient-structured cartilage scaffold by three-dimensional (3D) bioprinting, in which bone marrow stromal cell (BMSC)-laden anisotropic hydrogels micropatterns were used for heterogeneous chondrogenic differentiation and physically gradient synthetic poly (ε-caprolactone) (PCL) to impart mechanical strength. In vitro and in vivo, we demonstrated that gradient-structured cartilage scaffold displayed better cartilage repair effect. The heterogeneous cartilage tissue maturation and blood vessel ingrowth were mediated by a pore-size-dependent mechanism and HIF1α/FAK axis activation. In summary, our results provided a theoretical basis for employing 3D bioprinting gradient-structured constructs for anisotropic cartilage regeneration and revealed HIF1α/FAK axis as a crucial regulator for cell-material interactions, so as to provide a new perspective for cartilage regeneration and repair.
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Affiliation(s)
- Ye Sun
- Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Jiangsu, China.
| | - Qiang Wu
- Clinical and Translational Research Center for 3D Printing Technology, Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuxin Zhang
- Department of Rehabilitation Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Huangpu District, Shanghai, People's Republic of China
| | - Kerong Dai
- Clinical and Translational Research Center for 3D Printing Technology, Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yongzhong Wei
- Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Jiangsu, China
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11
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Abstract
It is known that iron is found as a trace element in bone tissue, the main inorganic constituent of which is hydroxyapatite. Therefore, iron-doped hydroxyapatite (HApFe) materials could be new alternatives for many biomedical applications. A facile dip coating process was used to elaborate the iron-doped hydroxyapatite (HApFe) nanocomposite coatings. The HApFe suspension used to prepare the coatings was achieved using a co-precipitation method, which was adapted in the laboratory. The quality of the HApFe suspension was assessed through dynamic light scattering (DLS), ultrasonic measurements, and zeta potential values. The hydroxyapatite XRD patterns were observed in the HApFe nanocomposite with no significant shifting of peak positions, thus suggesting that the incorporation of iron did not significantly modify the hydroxyapatite structure. The morphology of the HApFe nanoparticles was evaluated using transmission electron microscopy (TEM). Scanning electron microscopy (SEM) was used in order to investigate the morphologies of HApFe particles and coatings, while their chemical compositions were assessed using energy-dispersive X-ray spectroscopy (EDS). The SEM results suggested that the HApFe consists mainly of spherical nanometric particles and that the surfaces of the coatings are continuous and homogeneous. Additionally, the EDS spectra highlighted the purity of the samples and confirmed the presence of calcium, phosphorous, and iron in the analyzed sample. The in vitro cytotoxicity of the HApFe suspensions and coatings was evidenced using osteoblast cells. The MTT assay showed that both the HApFe suspensions and coatings exhibited biocompatible properties.
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12
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Raghunathan V, Edwards SG, Leonard BC, Kim S, Evashenk AT, Song Y, Rewinski E, Marangakis Price A, Hoehn A, Chang C, Reilly CM, Muppala S, Murphy CJ, Thomasy SM. Differential effects of Hsp90 inhibition on corneal cells in vitro and in vivo. Exp Eye Res 2020; 202:108362. [PMID: 33220237 DOI: 10.1016/j.exer.2020.108362] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 10/30/2020] [Accepted: 11/13/2020] [Indexed: 10/23/2022]
Abstract
The transformation of quiescent keratocytes to activated fibroblasts and myofibroblasts (KFM transformation) largely depends on transforming growth factor beta (TGFβ) signaling. Initiation of the TGFβ signaling cascade results from binding of TGFβ to the labile type I TGFβ receptor (TGFβRI), which is stabilized by the 90 kDa heat shock protein (Hsp90). Since myofibroblast persistence within the corneal stroma can result in stromal haze and corneal fibrosis in patients undergoing keratorefractive therapy, modulation of TGFβ signaling through Hsp90 inhibition would represent a novel approach to prevent myofibroblast persistence. In vitro, rabbit corneal fibroblasts (RCFs) or stratified immortalized human corneal epithelial cells (hTCEpi) were treated with a Hsp90 inhibitor (17AAG) in the presence/absence of TGFβ1. RCFs were cultured either on tissue culture plastic, anisotropically patterned substrates, and hydrogels of varying stiffness. Cellular responses to both cytoactive and variable substrates were assessed by morphologic changes to the cells, and alterations in expression patterns of key keratocyte and myofibroblast proteins using PCR, Western blotting and immunocytochemistry. Transepithelial electrical resistance (TEER) measurements were performed to establish epithelial barrier integrity. In vivo, the corneas of New Zealand White rabbits were wounded by phototherapeutic keratectomy (PTK) and treated with 17AAG (3× or 6× daily) either immediately or 7 days after wounding for 28 days. Rabbits underwent clinical ophthalmic examinations, SPOTS scoring and advanced imaging on days 0, 1, 3, 7, 10, 14, 21 and 28. On day 28, rabbits were euthanized and histopathology/immunohistochemistry was performed. In vitro data demonstrated that 17AAG inhibited KFM transformation with the de-differentiation of spindle shaped myofibroblasts to dendritic keratocyte-like cells accompanied by significant upregulation of corneal crystallins and suppression of myofibroblast markers regardless of TGFβ1 treatment. RCFs cultured on soft hydrogels or patterned substrates exhibited elevated expression of α-smooth muscle actin (αSMA) in the presence of 17AAG. Treatment of hTCEpi cells disrupted zonula occludens 1 (ZO-1) adherens junction formation. In vivo, there were no differences detected in nearly all clinical parameters assessed between treatment groups. However, rabbits treated with 17AAG developed greater stromal haze formation compared with controls, irrespective of frequency of administration. Lastly, there was increased αSMA positive myofibroblasts in the stroma of 17AAG treated animals when compared with controls. Hsp90 inhibition promoted reversion of the myofibroblast to keratocyte phenotype, although this only occurred on rigid substrates. By contrast, in vivo Hsp90 inhibition was detrimental to corneal wound healing likely due to impairment in corneal epithelial closure and barrier function restoration. Collectively, our data demonstrated a strong interplay in vitro between biophysical cues and soluble signaling molecules in determining corneal stromal cell phenotype.
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Affiliation(s)
- VijayKrishna Raghunathan
- Department of Basic Sciences, United States; The Ocular Surface Institute, College of Optometry, University of Houston, Houston, TX, United States.
| | - Sydney Garrison Edwards
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, United States
| | - Brian C Leonard
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, United States
| | - Soohyun Kim
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, United States
| | - Alexander T Evashenk
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, United States
| | - Yeonju Song
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, United States
| | - Eva Rewinski
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, United States
| | - Ariana Marangakis Price
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, United States
| | - Alyssa Hoehn
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, United States
| | - Connor Chang
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, United States
| | - Christopher M Reilly
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, United States
| | - Santoshi Muppala
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, United States
| | - Christopher J Murphy
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, United States; Department of Ophthalmology and Vision Science, School of Medicine, University of California, Davis, Davis, CA, United States
| | - Sara M Thomasy
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, United States; Department of Ophthalmology and Vision Science, School of Medicine, University of California, Davis, Davis, CA, United States.
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13
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Production of High Silicon-Doped Hydroxyapatite Thin Film Coatings via Magnetron Sputtering: Deposition, Characterisation, and In Vitro Biocompatibility. COATINGS 2020. [DOI: 10.3390/coatings10020190] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
In recent years, it has been found that small weight percent additions of silicon to HA can be used to enhance the initial response between bone tissue and HA. A large amount of research has been concerned with bulk materials, however, only recently has the attention moved to the use of these doped materials as coatings. This paper focusses on the development of a co-RF and pulsed DC magnetron sputtering methodology to produce a high percentage Si containing HA (SiHA) thin films (from 1.8 to 13.4 wt.%; one of the highest recorded in the literature to date). As deposited thin films were found to be amorphous, but crystallised at different annealing temperatures employed, dependent on silicon content, which also lowered surface energy profiles destabilising the films. X-ray photoelectron spectroscopy (XPS) was used to explore the structure of silicon within the films which were found to be in a polymeric (SiO2; Q4) state. However, after annealing, the films transformed to a SiO44−, Q0, state, indicating that silicon had substituted into the HA lattice at higher concentrations than previously reported. A loss of hydroxyl groups and the maintenance of a single-phase HA crystal structure further provided evidence for silicon substitution. Furthermore, a human osteoblast cell (HOB) model was used to explore the in vitro cellular response. The cells appeared to prefer the HA surfaces compared to SiHA surfaces, which was thought to be due to the higher solubility of SiHA surfaces inhibiting protein mediated cell attachment. The extent of this effect was found to be dependent on film crystallinity and silicon content.
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14
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Li G, Li S, Zhang L, Chen S, Sun Z, Li S, Zhang L, Yang Y. Construction of Biofunctionalized Anisotropic Hydrogel Micropatterns and Their Effect on Schwann Cell Behavior in Peripheral Nerve Regeneration. ACS APPLIED MATERIALS & INTERFACES 2019; 11:37397-37410. [PMID: 31525950 DOI: 10.1021/acsami.9b08510] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Hydrogels have promising application in tissue regeneration due to their excellent physicochemical and biocompatible properties, whereas anisotropic micropatterns are been proven to directionally induce cell alignment and accelerate cell migration. However, an effect of biofunctionalized anisotropic hydrogel micropatterns on nerve regeneration has rarely been reported. In this study, the anisotropic polyacrylamide (PAM) hydrogel micropatterns with aligned ridge/groove structures were first prepared via in situ free radical polymerization and micromolding, and then biofunctionalized using YIGSR peptide for better promoting cell growth. The morphology, swelling ratio, wettability, mechanical properties, and stability of the prepared hydrogel were characterized. The successful immobilization of YIGSR peptide on the PAM hydrogel was monitored using FTIR, immunofluorescence staining, and ELISA. The effects on adhesion, directional growth, and biological function of Schwann cells were evaluated. The results displayed that the anisotropic PAM hydrogel micropatterns with inner porous structure possessed good stability, swelling, and mechanical properties. The YIGSR peptide could be well immobilized on hydrogel micropatterns with a percentage of 62.6%. The biofunctionalized anisotropic hydrogel micropatterns could effectively regulate the orientation growth of Schwann cells, and obviously up-regulate BDNF (40%) and β-actin (50%) expression compared with single hydrogel micropatterns, without negatively affecting the normal secretion of neurotropic factors by Schwann cells. To the best of our knowledge, this is the first time to study the construction and effect of biofunctionalized anisotropic hydrogel micropatterns on nerve regeneration, which may provide an experimental and theoretical basis for the design and development of artificial implants for nerve regeneration application.
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Affiliation(s)
| | - Shenjie Li
- Medical School of Nantong University , 226001 , Nantong , P.R. China
| | | | | | - Zedong Sun
- Medical School of Nantong University , 226001 , Nantong , P.R. China
| | - Siqi Li
- Medical School of Nantong University , 226001 , Nantong , P.R. China
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15
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Mariappan N. Current trends in Nanotechnology applications in surgical specialties and orthopedic surgery. ACTA ACUST UNITED AC 2019. [DOI: 10.13005/bpj/1739] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Nanotechnology is manipulation of matter on atomic, molecular and supramolecular scale. It has extensive range of applications in various branches of science including molecular biology, Health and medicine, materials, electronics, transportation, drugs and drug delivery, chemical sensing, space exploration, energy, environment, sensors, diagnostics, microfabrication, organic chemistry and biomaterials. Nanotechnology involves innovations in drug delivery,fabric design, reactivity and strength of material and molecular manufacturing. Nanotechnology applications are spread over almost all surgical specialties and have revolutionized treatment of various medical and surgical conditions. Clinically relevant applications of nanotechnology in surgical specialties include development of surgical instruments, suture materials, imaging, targeted drug therapy, visualization methods and wound healing techniques. Management of burn wounds and scar is an important application of nanotechnology.Prevention, diagnosis, and treatment of various orthopedic conditions are crucial aspects of technology for functional recovery of patients. Improvement in standard of patient care,clinical trials, research, and development of medical equipments for safe use are improved with nanotechnology. They have a potential for long-term good results in a variety of surgical specialties including orthopedic surgery in the years to come.
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Affiliation(s)
- N. Mariappan
- Department of Hand Surgery, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra University (deemed), Porur, Chennai, India
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16
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Cell Morphology on Poly(methyl methacrylate) Microstructures as Function of Surface Energy. Int J Biomater 2019; 2019:2393481. [PMID: 31186649 PMCID: PMC6521382 DOI: 10.1155/2019/2393481] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Revised: 03/22/2019] [Accepted: 04/07/2019] [Indexed: 12/24/2022] Open
Abstract
Whilst the significance of substrate topography as a regulator of cell function is well established, a systematic analysis of the principles underlying this is still unavailable. Here we evaluate the hypothesis that surface energy plays a decisive role in substrate-mediated modulation of cell phenotype by evaluation of cell behaviour on synthetic microstructures exhibiting pronounced differences in surface energy. These microstructures, specifically cubes and walls, were fabricated from a biocompatible base polymer, poly(methyl methacrylate), by variotherm injection molding. The dimensions of the cubes were 1 μm x 1 μm x 1 μm (height x width x length) with a periodicity of 1:1 and 1:5 and the dimensions of the walls 1 μm x 1 μm x 15 mm (height x width x length) with a periodicity of 1:1 and 1:5. Mold inserts were made by lithography and electroplating. The surface energy of the resultant microstructures was determined by static contact angle measurements. Light scanning microscopy of the morphology of NT2/D1 and MC3T3-E1 preosteoblast cells cultured on structured PMMA samples in both cases revealed a profound surface energy dependence. “Walls” appeared to promote significant cell elongation, whilst a lack of cell adhesion was observed on “cubes” with the lowest periodicity. Contact angle measurements on walls revealed enhanced surface energy anisotropy (55 mN/m max., 10 mN/m min.) causing a lengthwise spreading of the test liquid droplet, similar to cell elongation. Surface energy measurements for cubes revealed increased isotropic hydrophobicity (87° max., H2O). A critical water contact angle of ≤ 80° appears to be necessary for adequate cell adhesion. A “switch” for cell adhesion and subsequently cell growth could therefore be applied by, for example, adjusting the periodicity of hydrophobic structures. In summary cell elongation on walls and a critical surface energy level for cell adhesion could be produced for NT2/D1 and MC3T3-E1 cells by symmetrical and asymmetrical energy barrier levels. We, furthermore, propose a water-drop model providing a common physicochemical cause regarding similar cell/droplet geometries and cell adhesion on the investigated microstructures.
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17
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Chen S, Du C. [Preparation and osteogenic properties of poly ( L-lactic acid)/lecithin porous scaffolds with open pore structure]. ZHONGGUO XIU FU CHONG JIAN WAI KE ZA ZHI = ZHONGGUO XIUFU CHONGJIAN WAIKE ZAZHI = CHINESE JOURNAL OF REPARATIVE AND RECONSTRUCTIVE SURGERY 2019; 32:1123-1130. [PMID: 30701727 DOI: 10.7507/1002-1892.201804127] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Objective To investigate the preparation and osteogenic properties of poly ( L-lactic acid)(PLLA)/lecithin porous scaffolds with open pore structure. Methods PLLA/lecithin porous scaffolds with different lecithin contents (0, 5%, 10%, 20%, 30%, 40%, 50%) were prepared by thermally induced phase separation (groups A, B, C, D, E, F, and G, respectively). Scanning electron microscopy (SEM) was used to observe the surface morphology of the scaffolds. Wide-angle X-ray diffraction (XRD) and differential scanning calorimetry (DSC) were used to detect the crystallinity of the scaffolds. The water uptake ability of the scaffolds was measured. The cell growth and viability of bone marrow mesenchymal stem cells (BMSCs) of mouse on each scaffold was assessed by cell counting kit 8 (CCK-8) method. The osteogenic differentiation ability of BMSCs on each scaffold was evaluated by alkaline phosphatase (ALP) activity. Finally, a critical-size rat calvarial bone defect model was used to evaluate the osteogenesis of the scaffolds in vivo. Micro-CT was used to reconstruct the three-dimensional model of the defect area, and the bone volume and bone mineral density were quantitatively analyzed. Results SEM results showed that the lecithin could slightly reduce the pore size; when lecithin content was 50%, platelet-like structure could be observed on the scaffolds. Wide angle XRD and DSC showed that the crystallinity of scaffolds gradually decreased with the increase of lecithin content. The water uptake ability test showed that the hydrophilicity of scaffolds increased with the increase of lecithin content. CCK-8 assay showed that cell activity gradually increased with the increase of culture time. After 7 days of culture, the absorbance ( A) value of groups C, D, E, and F were significantly higher than that of groups A, B, and G ( P<0.05), but no significant difference was found among groups C, D, E, and F ( P>0.05). After 14 days of osteogenic induction, with the increase of lecithin content, there was a significant difference in ALP activity of each group. The ALP activity in groups D, E, F, and G were significantly higher than that in groups A, B, and C ( P<0.05). In vivo, the results of Micro-CT examination and bone volume and bone mineral density showed that the scaffolds with 30% lecithin had the best repairing effect. Conclusion Prepared by thermally induced phase separation, the cytocompatibility, osteogenic differentiation, and bone repair ability of the PLLA/lecithin porous scaffold is obviously better than that of pure PLLA scaffold. PLLA/lecithin porous scaffold with suitable lecithin content is a promising scaffold material for bone tissue engineering.
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Affiliation(s)
- Si Chen
- Department of Biomedical Engineering, School of Materials Science and Engineering, South China University of Technology, Guangzhou Guangdong, 510641, P.R.China;National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou Guangdong, 510006, P.R.China;Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou Guangdong, 510006, P.R.China
| | - Chang Du
- Department of Biomedical Engineering, School of Materials Science and Engineering, South China University of Technology, Guangzhou Guangdong, 510641, P.R.China;National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou Guangdong, 510006, P.R.China;Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou Guangdong, 510006,
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18
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Zarka R, Horev MB, Volberg T, Neubauer S, Kessler H, Spatz JP, Geiger B. Differential Modulation of Platelet Adhesion and Spreading by Adhesive Ligand Density. NANO LETTERS 2019; 19:1418-1427. [PMID: 30649888 PMCID: PMC6437653 DOI: 10.1021/acs.nanolett.8b03513] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Revised: 01/08/2019] [Indexed: 05/25/2023]
Abstract
Platelets play a major role in hemostasis and thrombosis, by binding to the underlying extracellular matrix around injured blood vessels, via integrin receptors. In this study, we investigated the effects of adhesive ligand spacing on the stability of platelets' adhesion and the mode of their spreading on extracellular surfaces. Toward this end, we have examined the differential adhesion and spreading of human platelets onto nanogold-patterned surfaces, functionalized with the αIIbβ3 integrin ligand, SN528. Combining light- and scanning electron-microscopy, we found that interaction of platelets with surfaces coated with SN528 at spacing of 30-60 nm induces the extension of filopodia through which the platelets stably attach to the nanopatterned surface and spread on it. Increasing the nanopattern-gold spacing to 80-100 nm resulted in a dramatic reduction (>95%) in the number of adhering platelets. Surprisingly, a further increase in ligand spacing to 120 nm resulted in platelet binding to the surface at substantially larger numbers, yet these platelets remained discoid and were essentially devoid of filopodia and lamellipodia. These results indicate that the stimulation of filopodia extension by adhering platelets, and the consequent spreading on these surfaces depend on different ligand densities. Thus, the extension of filopodia occurs on surfaces with a ligand spacing of 100 nm or less, while the sustainability and growth of these initial adhesions and induction of extensive platelet adhesion and spreading requires lower ligand-to-ligand spacing (≤60 nm). The mechanisms underlying this differential ligand-density sensing by platelets, as well as the unexpected retention of discoid platelets on surfaces with even larger spacing (120 nm) are discussed.
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Affiliation(s)
- Revital Zarka
- Department
of Molecular Cell Biology, The Weizmann
Institute of Science, Rehovot 76100, Israel
| | - Melanie B. Horev
- Department
of Molecular Cell Biology, The Weizmann
Institute of Science, Rehovot 76100, Israel
| | - Tova Volberg
- Department
of Molecular Cell Biology, The Weizmann
Institute of Science, Rehovot 76100, Israel
| | - Stefanie Neubauer
- Institute
for Advanced Study (IAS) and Center of Integrated Protein Science,
Department of Chemistry, Technical University
of Munich, 85747 Garching, Germany
| | - Horst Kessler
- Institute
for Advanced Study (IAS) and Center of Integrated Protein Science,
Department of Chemistry, Technical University
of Munich, 85747 Garching, Germany
| | - Joachim P. Spatz
- Department
of Cellular Biophysics, Max Planck Institute
for Medical Research, Jahnstrasse 29, D-69120 Heidelberg, Germany
| | - Benjamin Geiger
- Department
of Molecular Cell Biology, The Weizmann
Institute of Science, Rehovot 76100, Israel
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19
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Aktas OC, Metzger W, Haidar A, Açil Y, Gülses A, Wiltfang J, Sacramento CM, Nothdurft FP. Enhancing adhesion and alignment of human gingival fibroblasts on dental implants. J Craniomaxillofac Surg 2019; 47:661-667. [PMID: 30846326 DOI: 10.1016/j.jcms.2019.02.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 01/27/2019] [Accepted: 02/04/2019] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Promoting the directional attachment of gingiva to the dental implant leads to the formation of tight connective tissue which acts as a seal against the penetration of oral bacteria. Such a directional growth is mostly governed by the surface texture. MATERIAL AND METHODS In this study, three different methods, mechanical structuring, chemical etching and laser treatment, have been explored for their applicability in promoting cellular attachment and alignment of human primary gingival fibroblasts (HGFIBs). RESULTS The effectiveness of mechanical structuring was shown as a simple and a cost-effective method to create patterns to align HGIFIBs. CONCLUSION Combining mechanical structuring with chemical etching enhanced both cellular attachment and the cellular alignment.
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Affiliation(s)
- Oral Cenk Aktas
- Institute for Materials Science, Christian-Albrechts-University Kiel, Germany
| | - Wolfgang Metzger
- Department of Trauma, Hand and Reconstructive Surgery, Saarland University, Homburg, Saar, Germany
| | - Ayman Haidar
- Department of Prosthetic Dentistry and Dental Materials Sciences, Saarland University, Homburg, Saar, Germany
| | - Yahya Açil
- Department of Oral and Maxillofacial Surgery, Christian-Albrecht-Universität zu Kiel, Kiel, Germany
| | - Aydin Gülses
- Department of Oral and Maxillofacial Surgery, Christian-Albrecht-Universität zu Kiel, Kiel, Germany
| | - Jörg Wiltfang
- Department of Oral and Maxillofacial Surgery, Christian-Albrecht-Universität zu Kiel, Kiel, Germany
| | - Catharina Marques Sacramento
- Department of Prosthesis and Periodontology, Division of Periodontics, Piracicaba Dental School, University of Campinas, Piracicaba, Brazil
| | - Frank Philipp Nothdurft
- Department of Prosthetic Dentistry and Dental Materials Sciences, Saarland University, Homburg, Saar, Germany.
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20
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Luo B, Tian L, Chen N, Ramakrishna S, Thakor N, Yang IH. Electrospun nanofibers facilitate better alignment, differentiation, and long-term culture in an in vitro model of the neuromuscular junction (NMJ). Biomater Sci 2019; 6:3262-3272. [PMID: 30402630 DOI: 10.1039/c8bm00720a] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
The neuromuscular junction (NMJ) is a specialized synapse between motor neurons and the muscle fibers they innervate. Due to the complexity of various signalling molecules and pathways, in vivo NMJs are difficult to study. Therefore, in vitro motor neuron-muscle co-culture plays a pivotal role in studying the mechanisms of NMJ formation associated with neurodegenerative diseases. There is a growing need to develop novel methodologies that can be used to develop long-term cultures of NMJs. To date, there have been few studies on NMJ development and long-term maintenance of the system, which is also the main challenge for the current in vitro models of NMJs. In this study, we demonstrate a long-term co-culture system of primary embryonic motor neurons from Sprague-Dawley rats and C2C12 cells on both random and aligned electrospun polylactic acid (PLA) nanofibrous scaffolds. This is the first study to explore the role of electrospun nanofibers in the long-term maintenance of NMJs. PLA nanofibrous scaffolds provide better contact guidance for C2C12 cells aligning along the fibers, thus guiding myotube formation. We can only maintain the co-culture system on a conventional glass substrate for 2 weeks, whilst 55% and 70% of the cells still survived on random and aligned PLA substrates after 7 weeks. Our nanofiber-based long-term co-culture system is used as an important tool for the fundamental research of NMJs.
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Affiliation(s)
- Baiwen Luo
- Singapore Institute for Neurotechnology, National University of Singapore, 28 Medical Drive, #05-COR, Singapore 119077. inhong.yang.@ku.ac.ae
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21
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Molina BG, Cianga L, Bendrea AD, Cianga I, Alemán C, Armelin E. An amphiphilic, heterografted polythiophene copolymer containing biocompatible/biodegradable side chains for use as an (electro)active surface in biomedical applications. Polym Chem 2019. [DOI: 10.1039/c9py00926d] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Design of an amphiphilic heterografted block copolymer composed of a hydrophobic core backbone and both hydrophilic side chains, able to detect the redox reaction of NADH.
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Affiliation(s)
- Brenda G. Molina
- Departament d'Enginyeria Química
- EEBE
- Universitat Politècnica de Catalunya
- Barcelona
- Spain
| | - Luminita Cianga
- “Petru Poni” Institute of Macromolecular Chemistry
- Iasi
- Romania
| | | | - Ioan Cianga
- “Petru Poni” Institute of Macromolecular Chemistry
- Iasi
- Romania
| | - Carlos Alemán
- Departament d'Enginyeria Química
- EEBE
- Universitat Politècnica de Catalunya
- Barcelona
- Spain
| | - Elaine Armelin
- Departament d'Enginyeria Química
- EEBE
- Universitat Politècnica de Catalunya
- Barcelona
- Spain
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Chen X, Fan H, Deng X, Wu L, Yi T, Gu L, Zhou C, Fan Y, Zhang X. Scaffold Structural Microenvironmental Cues to Guide Tissue Regeneration in Bone Tissue Applications. NANOMATERIALS (BASEL, SWITZERLAND) 2018; 8:E960. [PMID: 30469378 PMCID: PMC6266401 DOI: 10.3390/nano8110960] [Citation(s) in RCA: 109] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Revised: 11/15/2018] [Accepted: 11/17/2018] [Indexed: 02/07/2023]
Abstract
In the process of bone regeneration, new bone formation is largely affected by physico-chemical cues in the surrounding microenvironment. Tissue cells reside in a complex scaffold physiological microenvironment. The scaffold should provide certain circumstance full of structural cues to enhance multipotent mesenchymal stem cell (MSC) differentiation, osteoblast growth, extracellular matrix (ECM) deposition, and subsequent new bone formation. This article reviewed advances in fabrication technology that enable the creation of biomaterials with well-defined pore structure and surface topography, which can be sensed by host tissue cells (esp., stem cells) and subsequently determine cell fates during differentiation. Three important cues, including scaffold pore structure (i.e., porosity and pore size), grain size, and surface topography were studied. These findings improve our understanding of how the mechanism scaffold microenvironmental cues guide bone tissue regeneration.
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Affiliation(s)
- Xuening Chen
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
| | - Hongyuan Fan
- Scholl of Manufacturing Science and Engineering, Sichuan University, Chengdu 610065, China.
| | - Xiaowei Deng
- Department of Civil Engineering, The University of Hongkong, Pokfulam, Hongkong 999077, China.
| | - Lina Wu
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
| | - Tao Yi
- Scholl of Manufacturing Science and Engineering, Sichuan University, Chengdu 610065, China.
| | - Linxia Gu
- Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588-0526, USA.
| | - Changchun Zhou
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
| | - Yujiang Fan
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
| | - Xingdong Zhang
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
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Biomaterials in Tendon and Skeletal Muscle Tissue Engineering: Current Trends and Challenges. MATERIALS 2018; 11:ma11071116. [PMID: 29966303 PMCID: PMC6073924 DOI: 10.3390/ma11071116] [Citation(s) in RCA: 90] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Revised: 06/20/2018] [Accepted: 06/25/2018] [Indexed: 12/17/2022]
Abstract
Tissue engineering is a promising approach to repair tendon and muscle when natural healing fails. Biohybrid constructs obtained after cells’ seeding and culture in dedicated scaffolds have indeed been considered as relevant tools for mimicking native tissue, leading to a better integration in vivo. They can also be employed to perform advanced in vitro studies to model the cell differentiation or regeneration processes. In this review, we report and analyze the different solutions proposed in literature, for the reconstruction of tendon, muscle, and the myotendinous junction. They classically rely on the three pillars of tissue engineering, i.e., cells, biomaterials and environment (both chemical and physical stimuli). We have chosen to present biomimetic or bioinspired strategies based on understanding of the native tissue structure/functions/properties of the tissue of interest. For each tissue, we sorted the relevant publications according to an increasing degree of complexity in the materials’ shape or manufacture. We present their biological and mechanical performances, observed in vitro and in vivo when available. Although there is no consensus for a gold standard technique to reconstruct these musculo-skeletal tissues, the reader can find different ways to progress in the field and to understand the recent history in the choice of materials, from collagen to polymer-based matrices.
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Photopolymerized Microfeatures Guide Adult Spiral Ganglion and Dorsal Root Ganglion Neurite Growth. Otol Neurotol 2018; 39:119-126. [PMID: 29227456 DOI: 10.1097/mao.0000000000001622] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
HYPOTHESIS Microtopographical patterns generated by photopolymerization of methacrylate polymer systems will direct growth of neurites from adult neurons, including spiral ganglion neurons (SGNs). BACKGROUND Cochlear implants (CIs) provide hearing perception to patients with severe to profound hearing loss. However, their ability to encode complex auditory stimuli is limited due, in part, to poor spatial resolution caused by spread of the electrical currents in the inner ear. Directing the regrowth of SGN peripheral processes towards stimulating electrodes could help reduce current spread and improve spatial resolution provided by the CI. Previous work has demonstrated that micro- and nano-scale patterned surfaces precisely guide the growth of neurites from a variety of neonatal neurons including SGNs. Here, we sought to determine the extent to which adult neurons likewise respond to these topographical surface features. METHODS Photopolymerization was used to fabricate methacrylate polymer substrates with micropatterned surfaces of varying amplitudes and periodicities. Dissociated adult dorsal root ganglion neurons (DRGNs) and SGNs were cultured on these surfaces and the alignment of the neurite processes to the micropatterns was determined. RESULTS Neurites from both adult DRGNs and SGNs significantly aligned to the patterned surfaces similar to their neonatal counterparts. Further DRGN and SGN neurite alignment increased as the amplitude of the microfeatures increased. Decreased pattern periodicity also improved neurite alignment. CONCLUSION Microscale surface topographic features direct the growth of adult SGN neurites. Topographical features could prove useful for guiding growth of SGN peripheral axons towards a CI electrode array.
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Ankam S, Teo BKK, Pohan G, Ho SWL, Lim CK, Yim EKF. Temporal Changes in Nucleus Morphology, Lamin A/C and Histone Methylation During Nanotopography-Induced Neuronal Differentiation of Stem Cells. Front Bioeng Biotechnol 2018; 6:69. [PMID: 29904629 PMCID: PMC5990852 DOI: 10.3389/fbioe.2018.00069] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Accepted: 05/09/2018] [Indexed: 01/14/2023] Open
Abstract
Stem cell differentiation can be regulated by biophysical cues such as nanotopography. It involves sensing and integration of these biophysical cues into their transcriptome with a mechanism that is yet to be discovered. In addition to the cytoskeletal and focal adhesion remodeling, nanotopography has also been shown to modulate nucleus morphology. Here, we studied the effect of nanotopography on the temporal changes in nuclei of human embryonic stem cells (hESCs) and human mesenchymal stem cells (hMSCs). Using a high throughput Multi-architecture (MARC) chip analysis, the circularity of the stem cell nuclei changed significantly on different patterns. Human ESCs and MSCs showed different temporal changes in nucleus morphology, lamin A/C expression and histone methylation during topography-induced neuronal differentiation. In hESCs, the expression of nuclear matrix protein, lamin A/C during neuronal differentiation of hESCs on PDMS samples were weakly detected in the first 7 days of differentiation. The histone 3 trimethylation on Lysine 9 (H3K9me3) decreased after differentiation initiated and showed temporal changes in their expression and organization during neuronal differentiation. In hMSCs, the expression of lamin A/C was significantly increased after the first 24 h of cell culture. The quantitative analysis of histone methylation also showed a significant increase in hMSCs histone methylation on 250 nm anisotropic nanogratings within the first 24 h of seeding. This reiterates the importance of cell-substrate sensing within the first 24 h for adult stem cells. The lamin A/C expression and histone methylation shows a correlation of epigenetic changes in early events of differentiation, giving an insight on how extracellular nanotopographical cues are transduced into nuclear biochemical signals. Collectively, these results provide more understanding into the nuclear regulation of the mechanotransduction of nanotopographical cues in stem cell differentiation.
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Affiliation(s)
- Soneela Ankam
- Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore
| | - Benjamin K K Teo
- Mechanobiology Institute Singapore, National University of Singapore, Singapore, Singapore
| | - Grace Pohan
- Department of Chemical Engineering, University of Waterloo, Waterloo, ON, Canada
| | - Shawn W L Ho
- Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore
| | - Choon K Lim
- Mechanobiology Institute Singapore, National University of Singapore, Singapore, Singapore
| | - Evelyn K F Yim
- Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore.,Mechanobiology Institute Singapore, National University of Singapore, Singapore, Singapore.,Department of Chemical Engineering, University of Waterloo, Waterloo, ON, Canada.,Department of Surgery, National University of Singapore, Singapore, Singapore
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26
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Asthana A, White CM, Douglass M, Kisaalita WS. Evaluation of cellular adhesion and organization in different microporous polymeric scaffolds. Biotechnol Prog 2018; 34:505-514. [DOI: 10.1002/btpr.2627] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2017] [Revised: 01/18/2018] [Indexed: 12/11/2022]
Affiliation(s)
- Amish Asthana
- School of Chemical, Materials, and Biomedical Engineering, Cellular Bioengineering Laboratory, College of Engineering, Driftmier Engineering Center; University of Georgia; Athens GA 30602
| | - Charles McRae White
- School of Chemical, Materials, and Biomedical Engineering, Cellular Bioengineering Laboratory, College of Engineering, Driftmier Engineering Center; University of Georgia; Athens GA 30602
| | - Megan Douglass
- School of Chemical, Materials, and Biomedical Engineering, Cellular Bioengineering Laboratory, College of Engineering, Driftmier Engineering Center; University of Georgia; Athens GA 30602
| | - William S. Kisaalita
- School of Chemical, Materials, and Biomedical Engineering, Cellular Bioengineering Laboratory, College of Engineering, Driftmier Engineering Center; University of Georgia; Athens GA 30602
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27
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Giavaresi G, Giardino R, Ambrosio L, Battiston G, Gerbasi R, Fini M, Rimondini L, Torricelli P. In Vitro Biocompatibility of Titanium Oxide for Prosthetic Devices Nanostructured by Low Pressure Metal-Organic Chemical Vapor Deposition. Int J Artif Organs 2018; 26:774-80. [PMID: 14521176 DOI: 10.1177/039139880302600811] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Metal-Organic Chemical Vapor Deposition (MOCVD) has recently been proposed to coat orthopedic and dental prostheses with metal nanostructured oxide films through the decomposition of oxygenated compounds (single-source precursors) or the reaction of oxygen-free metal compounds with oxygenating agents. The present study was carried out to assess the in vitro biocompatibility in terms of cell proliferation and activation, of commercially pure Ti (control material: TI/MA) coated with nanostructured TiO2 film by MOCVD (Ti/MOCVD) using osteoblast-like cell cultures (MG-63). Evaluations were performed at 3, 7 and 14 days. Cell proliferation showed a similar trend for Ti/MA and Ti/MOCVD compared to polystyrene; cell number increased with time from seeding to day 7 (p < 0.005), and then decreased progressively until day 14 (ranging from −14% to −47%). The ALP level and OC production showed no significant differences between Ti/MOCVD and Ti/MA at each experimental time. Significantly higher ALP levels were found in Ti/MA at 3 days and in Ti/MOCVD at 7 and 14 days when compared to the polystyrene group. OC production decreased over time and the highest values were observed at 3 days, when it was significantly higher in the Ti/MA than in the polystyrene group (50%, p < 0.05). CICP synthesis was positively affected by the presence of Ti/MOCVD and was higher in Ti/MOCVD than in the polystyrene group. No significant differences were found between Ti/MOCVD and Ti/MA in terms of IL-6 and TGF-ß1 synthesis at any experimental time. In conclusion, the current findings demonstrate that the nanostructured TiO2 coating positively affects the osteoblast-like cell behavior in terms of cell proliferation and activity, thus confirming its high level of in vitro biocompatibility in accordance with expectations.
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Affiliation(s)
- G Giavaresi
- Experimental Surgery Department, Research Institute Codivilla-Putti, Rizzoli Orthopedic Institute, Bologna, Italy
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Soft Lithography and Minimally Human Invasive Technique for Rapid Screening of Oral Biofilm Formation on New Microfabricated Dental Material Surfaces. Int J Dent 2018; 2018:4219625. [PMID: 29593793 PMCID: PMC5821979 DOI: 10.1155/2018/4219625] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2017] [Accepted: 11/19/2017] [Indexed: 11/18/2022] Open
Abstract
Introduction Microfabrication offers opportunities to study surface concepts focused to reduce bacterial adhesion on implants using human minimally invasive rapid screening (hMIRS). Wide information is available about cell/biomaterial interactions using eukaryotic and prokaryotic cells on surfaces of dental materials with different topographies, but studies using human being are still limited. Objective To evaluate a synergy of microfabrication and hMIRS to study the bacterial adhesion on micropatterned surfaces for dental materials. Materials and Methods Micropatterned and flat surfaces on biomedical PDMS disks were produced by soft lithography. The hMIRS approach was used to evaluate the total oral bacterial adhesion on PDMS surfaces placed in the oral cavity of five volunteers (the study was approved by the University Ethical Committee). After 24 h, the disks were analyzed using MTT assay and light microscopy. Results In the present pilot study, microwell structures were microfabricated on the PDMS surface via soft lithography with a spacing of 5 µm. Overall, bacterial adhesion did not significantly differ between the flat and micropatterned surfaces. However, individual analysis of two subjects showed greater bacterial adhesion on the micropatterned surfaces than on the flat surfaces. Significance Microfabrication and hMIRS might be implemented to study the cell/biomaterial interactions for dental materials.
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29
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Cui LH, Joo HJ, Kim DH, Seo HR, Kim JS, Choi SC, Huang LH, Na JE, Lim IR, Kim JH, Rhyu IJ, Hong SJ, Lee KB, Lim DS. Manipulation of the response of human endothelial colony-forming cells by focal adhesion assembly using gradient nanopattern plates. Acta Biomater 2018; 65:272-282. [PMID: 29037896 DOI: 10.1016/j.actbio.2017.10.026] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2017] [Revised: 10/12/2017] [Accepted: 10/12/2017] [Indexed: 12/18/2022]
Abstract
Nanotopography plays a pivotal role in the regulation of cellular responses. Nonetheless, little is known about how the gradient size of nanostructural stimuli alters the responses of endothelial progenitor cells without chemical factors. Herein, the fabrication of gradient nanopattern plates intended to mimic microenvironment nanotopography is described. The gradient nanopattern plates consist of nanopillars of increasing diameter ranges [120-200 nm (GP 120/200), 200-280 nm (GP 200/280), and 280-360 nm (GP 280/360)] that were used to screen the responses of human endothelial colony-forming cells (hECFCs). Nanopillars with a smaller nanopillar diameter caused the cell area and perimeter of hECFCs to decrease and their filopodial outgrowth to increase. The structure of vinculin (a focal adhesion marker in hECFCs) was also modulated by nanostructural stimuli of the gradient nanopattern plates. Moreover, Rho-associated protein kinase (ROCK) gene expression was significantly higher in hECFCs cultured on GP 120/200 than in those on flat plates (no nanopillars), and ROCK suppression impaired the nanostructural-stimuli-induced vinculin assembly. These results suggest that the gradient nanopattern plates generate size-specific nanostructural stimuli suitable for manipulation of the response of hECFCs, in a process dependent on ROCK signaling. This is the first evidence of size-specific nanostructure-sensing behavior of hECFCs. SIGNIFICANCE Nano feature surfaces are of growing interest as materials for a controlled response of various cells. In this study, we successfully fabricated gradient nanopattern plates to manipulate the response of blood-derived hECFCs without any chemical stimulation. Interestingly, we find that the sensitive nanopillar size for manipulation of hECFCs is range between 120 nm and 200 nm, which decreased the area and increased the filopodial outgrowth of hECFCs. Furthermore, we only modulate the nanopillar size to increase ROCK expression can be an attractive method for modulating the cytoskeletal integrity and focal adhesion of hECFCs.
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Affiliation(s)
- Long-Hui Cui
- Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, 145, Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea
| | - Hyung Joon Joo
- Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, 145, Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea
| | - Dae Hwan Kim
- School of Biomedical Engineering, College of Health Science, Korea University, 145, Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea
| | - Ha-Rim Seo
- Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, 145, Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea
| | - Jung Suk Kim
- School of Biomedical Engineering, College of Health Science, Korea University, 145, Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea
| | - Seung-Cheol Choi
- Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, 145, Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea
| | - Li-Hua Huang
- Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, 145, Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea
| | - Ji Eun Na
- Department of Anatomy, College of Medicine, Korea University, Seoul 02841, Republic of Korea
| | - I-Rang Lim
- Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, 145, Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea
| | - Jong-Ho Kim
- Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, 145, Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea
| | - Im Joo Rhyu
- Department of Anatomy, College of Medicine, Korea University, Seoul 02841, Republic of Korea
| | - Soon Jun Hong
- Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, 145, Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea
| | - Kyu Back Lee
- School of Biomedical Engineering, College of Health Science, Korea University, 145, Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea.
| | - Do-Sun Lim
- Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, 145, Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea.
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30
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Linklater DP, Juodkazis S, Ivanova EP. Nanofabrication of mechano-bactericidal surfaces. NANOSCALE 2017; 9:16564-16585. [PMID: 29082999 DOI: 10.1039/c7nr05881k] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/23/2023]
Abstract
The search for alternatives to the standard methods of preventing bacterial adhesion and biofilm formation on biotic and abiotic surfaces alike has led to the use of biomimetics to reinvent through nanofabrication methods, surfaces, whereby the nanostructured topography is directly responsible for bacterial inactivation through physico-mechanical means. Plant leaves, insect wings, and animal skin have been used to inspire the fabrication of synthetic high-aspect-ratio nanopillared surfaces, which can resist bacterial colonisation. The adaptation of bacteria to survive in the presence of antibiotics and their ability to form biofilms on conventional antibacterial surfaces has led to an increase in persistent infections caused by resistant strains of bacteria. This presents a worldwide health epidemic that can only be mitigated through the search for a new generation of biomaterials.
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Affiliation(s)
- Denver P Linklater
- Faculty of Life and Social Sciences, Swinburne University of Technology, Hawthorn, VIC 3122, Australia.
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31
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Liu XQ, Tang RZ. Biological responses to nanomaterials: understanding nano-bio effects on cell behaviors. Drug Deliv 2017; 24:1-15. [PMID: 29069934 PMCID: PMC8812585 DOI: 10.1080/10717544.2017.1375577] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Affiliation(s)
- Xi-Qiu Liu
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
| | - Rui-Zhi Tang
- Lab of Inflammation & Cancer, Institut de Génétique Moléculaire de Montpellier, Montpellier, France
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32
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Zeng YJ, Twan SC, Wang KW, Huang HH, Hsu YB, Wang CY, Lan MY, Lee SW. Enhanced Biocompatibility in Anodic TaO x Nanotube Arrays. NANOSCALE RESEARCH LETTERS 2017; 12:557. [PMID: 28975550 PMCID: PMC5626673 DOI: 10.1186/s11671-017-2325-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/18/2017] [Accepted: 09/25/2017] [Indexed: 06/07/2023]
Abstract
This study first investigates the biocompatibility of self-organized TaO x nanotube arrays with different nanotube diameters fabricated by electrochemical anodization. All as-anodized TaO x nanotubes were identified to be an amorphous phase. The transition in surface wettability with TaO x nanotube diameters can be explained based on Wenzel's model in terms of geometric roughness. In vitro biocompatibility evaluation further indicates that fibroblast cells exhibit an obvious wettability-dependent behavior on the TaO x nanotubes. The 35-nm-diameter TaO x nanotube arrays reveal the highest biocompatibility among all samples. This enhancement could be attributed to highly dense focal points provided by TaO x nanotubes due to higher surface hydrophilicity. This work demonstrates that the biocompatibility in Ta can be improved by forming TaO x nanotube arrays on the surface with appropriate nanotube diameter and geometric roughness.
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Affiliation(s)
- Yu-Jin Zeng
- Institute of Materials Science and Engineering, National Central University, Taoyuan, 320 Taiwan Republic of China
| | - Sheng-Chen Twan
- Institute of Materials Science and Engineering, National Central University, Taoyuan, 320 Taiwan Republic of China
| | - Kuan-Wen Wang
- Institute of Materials Science and Engineering, National Central University, Taoyuan, 320 Taiwan Republic of China
| | - Her-Hsiung Huang
- Department of Dentistry, National Yang-Ming University, Taipei, 11221 Taiwan Republic of China
| | - Yen-Bin Hsu
- Department of Otolaryngology Head and Neck Surgery, Taipei Veterans General Hospital, Taipei, 112 Taiwan Republic of China
- School of Medicine, National Yang-Ming University, Taipei, 112 Taiwan Republic of China
| | - Chien-Ying Wang
- Department of Emergency, Taipei Veterans General Hospital, Taipei, 112 Taiwan Republic of China
| | - Ming-Ying Lan
- Department of Otolaryngology Head and Neck Surgery, Taipei Veterans General Hospital, Taipei, 112 Taiwan Republic of China
- School of Medicine, National Yang-Ming University, Taipei, 112 Taiwan Republic of China
| | - Sheng-Wei Lee
- Institute of Materials Science and Engineering, National Central University, Taoyuan, 320 Taiwan Republic of China
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Skoog SA, Kumar G, Narayan RJ, Goering PL. Biological responses to immobilized microscale and nanoscale surface topographies. Pharmacol Ther 2017; 182:33-55. [PMID: 28720431 DOI: 10.1016/j.pharmthera.2017.07.009] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Cellular responses are highly influenced by biochemical and biomechanical interactions with the extracellular matrix (ECM). Due to the impact of ECM architecture on cellular responses, significant research has been dedicated towards developing biomaterials that mimic the physiological environment for design of improved medical devices and tissue engineering scaffolds. Surface topographies with microscale and nanoscale features have demonstrated an effect on numerous cellular responses, including cell adhesion, migration, proliferation, gene expression, protein production, and differentiation; however, relationships between biological responses and surface topographies are difficult to establish due to differences in cell types and biomaterial surface properties. Therefore, it is important to optimize implant surface feature characteristics to elicit desirable biological responses for specific applications. The goal of this work was to review studies investigating the effects of microstructured and nanostructured biomaterials on in vitro biological responses through fabrication of microscale and nanoscale surface topographies, physico-chemical characterization of material surface properties, investigation of protein adsorption dynamics, and evaluation of cellular responses in specific biomedical applications.
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Affiliation(s)
- Shelby A Skoog
- Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD, United States; Joint Department of Biomedical Engineering, University of North Carolina and North Carolina State University, Raleigh, NC, United States
| | - Girish Kumar
- Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD, United States
| | - Roger J Narayan
- Joint Department of Biomedical Engineering, University of North Carolina and North Carolina State University, Raleigh, NC, United States
| | - Peter L Goering
- Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD, United States.
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Gómez-Cerezo N, Sánchez-Salcedo S, Izquierdo-Barba I, Arcos D, Vallet-Regí M. In vitro colonization of stratified bioactive scaffolds by pre-osteoblast cells. Acta Biomater 2016; 44:73-84. [PMID: 27521495 DOI: 10.1016/j.actbio.2016.08.014] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2016] [Revised: 07/28/2016] [Accepted: 08/10/2016] [Indexed: 10/25/2022]
Abstract
UNLABELLED Mesoporous bioactive glass-polycaprolactone (MBG-PCL) scaffolds have been prepared by robocasting, a layer by layer rapid prototyping method, by stacking of individual strati. Each stratus was independently analyzed during the cell culture tests with MC3T3-E1 preosteblast-like cells. The presence of MBG stimulates the colonization of the scaffolds by increasing the cell proliferation and differentiation. MBG-PCL composites not only enhanced pre-osteoblast functions but also allowed cell movement along its surface, reaching the upper stratus faster than in pure PCL scaffolds. The cells behavior on each individual stratus revealed that the scaffolds colonization depends on the chemical stimuli supplied by the MBG dissolution and surface changes associated to the apatite-like formation during the bioactive process. Finally, scanning electron and fluorescence microscopy revealed that the kinetic of cell migration strongly depends on the architectural features of the scaffolds, in such a way that layers interconnections are used as migration routes to reach the farther scaffolds locations from the initial cells source. STATEMENT OF SIGNIFICANCE This manuscript provides new insights on cell behavior in bioceramic/polymer macroporous scaffolds prepared by rapid prototyping methods. The experiments proposed in this work have allowed the evaluation of cell behavior within the different levels of the scaffolds, i.e. from the initials source of cells towards the farther scaffold locations. We could demonstrate that the in vitro cell colonization is encouraged by the presence of a highly bioactive mesoporous glass (MBG). This bioceramic enhances the cell migration towards upper strati through the dissolution of chemical signals and the changes occurred on the scaffolds surface during the bioactive process. In addition the MBG promotes preosteblastic proliferation and differentiation respect to scaffolds made of pure polycaprolactone. Finally, this study reveals the significance of the architectural design to accelerate the cell colonization. These experiments put light on the factors that should be taken into account to accelerate the regeneration processes under in vivo conditions.
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Ngandu Mpoyi E, Cantini M, Reynolds PM, Gadegaard N, Dalby M, Salmerón-Sánchez M. Protein Adsorption as a Key Mediator in the Nanotopographical Control of Cell Behavior. ACS NANO 2016; 10:6638-47. [PMID: 27391047 PMCID: PMC4980054 DOI: 10.1021/acsnano.6b01649] [Citation(s) in RCA: 90] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/14/2023]
Abstract
Surface nanotopography is widely employed to control cell behavior and in particular controlled disorder has been shown to be important in cell differentiation/maturation. However, extracellular matrix proteins, such as fibronectin (FN), initially adsorbed on a biomaterial surface are known to mediate the interaction of synthetic materials with cells. In this work, we examine the effect of nanotopography on cell behavior through this adsorbed layer of adhesive proteins using a nanostructured polycarbonate surface comprising 150 nm-diameter pits originally defined using electron beam lithography. We address the effect of this nanopitted surface on FN adsorption and subsequently on cell morphology and behavior using C2C12 myoblasts. Wettability measurements and atomic force microscopy imaging showed that protein is adsorbed both within the interpits spaces and inside the nanopits. Cells responded to this coated nanotopography with the formation of fewer but larger focal adhesions and by mimicking the pit patterns within their cytoskeleton, nanoimprinting, ultimately achieving higher levels of myogenic differentiation compared to a flat control. Both focal adhesion assembly and nanoimprinting were found to be dependent on cell contractility and are adversely affected by the use of blebbistatin. Our results demonstrate the central role of the nanoscale protein interface in mediating cell-nanotopographical interactions and implicate this interface as helping control the mechanotransductive cascade.
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Affiliation(s)
- Elie Ngandu Mpoyi
- Division
of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow G12 8LT, United Kingdom
| | - Marco Cantini
- Division
of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow G12 8LT, United Kingdom
| | - Paul M. Reynolds
- Division
of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow G12 8LT, United Kingdom
| | - Nikolaj Gadegaard
- Division
of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow G12 8LT, United Kingdom
| | - Matthew
J. Dalby
- Center
for Cell Engineering, Institute of Molecular Cell and Systems Biology, University of Glasgow, Joseph Black Building, University Avenue, Glasgow G12 8QQ, United Kingdom
| | - Manuel Salmerón-Sánchez
- Division
of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow G12 8LT, United Kingdom
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36
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Wu T, Sha J, Peng Y, Chen X, Xie L, Ma Y, Turng LS. Fabrication of biocompatible nanohybrid shish-kebab-structured carbon nanotubes with a mussel-inspired layer. RSC Adv 2016. [DOI: 10.1039/c6ra21291c] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
The first report investigating the biocompatibility of the (polydopamine coated) carbon nanotubes/polymer nanohybrid shish-kebab structure for tissue engineering.
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Affiliation(s)
- Tong Wu
- Engineering Center of Efficient Green Process Equipment and Energy Conservation
- Ministry of Education
- East China University of Science and Technology
- Shanghai
- China
| | - Jin Sha
- Engineering Center of Efficient Green Process Equipment and Energy Conservation
- Ministry of Education
- East China University of Science and Technology
- Shanghai
- China
| | - Yiyan Peng
- Wisconsin Institute for Discovery
- University of Wisconsin-Madison
- Madison
- USA
| | - Xin Chen
- Engineering Center of Efficient Green Process Equipment and Energy Conservation
- Ministry of Education
- East China University of Science and Technology
- Shanghai
- China
| | - Linsheng Xie
- Engineering Center of Efficient Green Process Equipment and Energy Conservation
- Ministry of Education
- East China University of Science and Technology
- Shanghai
- China
| | - Yulu Ma
- Engineering Center of Efficient Green Process Equipment and Energy Conservation
- Ministry of Education
- East China University of Science and Technology
- Shanghai
- China
| | - Lih-Sheng Turng
- Wisconsin Institute for Discovery
- University of Wisconsin-Madison
- Madison
- USA
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37
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Allen J, Ryu J, Maggi A, Flores B, Greer JR, Desai T. Tunable Microfibers Suppress Fibrotic Encapsulation via Inhibition of TGFβ Signaling. Tissue Eng Part A 2015; 22:142-50. [PMID: 26507808 DOI: 10.1089/ten.tea.2015.0087] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Fibrotic encapsulation limits the efficacy and lifetime of implantable biomedical devices. Microtopography has shown promise in the regulation of myofibroblast differentiation, a key driver of fibrotic encapsulation. However, existing studies have not systematically isolated the requisite geometric parameters for suppression of myofibroblast differentiation via microtopography, and there has not been in vivo validation of this technology to date. To address these issues, a novel lamination method was developed to afford more control over topography dimensions. Specifically, in this study we focus on fiber length and its effect on myofibroblast differentiation. Fibroblasts cultured on films with microfibers exceeding 16 μm in length lost the characteristic morphology associated with myofibroblast differentiation, while shorter microfibers of 6 μm length failed to produce this phenotype. This increase in length corresponded to a 50% decrease in fiber stiffness, which acts as a mechanical cue to influence myofibroblast differentiation. Longer microfiber films suppressed expression of myofibroblast-specific genes (αSMA, Col1α2, and Col3α1) and TGFβ signaling components (TGFβ1, TβR2, and Smad3). About 16 μm long microfiber films subcutaneously implanted in a mouse wound-healing model generated a substantially thinner fibrotic capsule and less deposition of collagen in the wound bed. Together, these results identify a critical feature length threshold for microscale topography-mediated repression of fibrotic encapsulation. This study also demonstrates a simple and powerful strategy to improve surface biocompatibility and reduce fibrotic encapsulation around implanted materials.
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Affiliation(s)
- Jessica Allen
- 1 UCSF Department of Bioengineering and Therapeutic Sciences, San Francisco , California
| | - Jubin Ryu
- 2 UCSF Department of Dermatology, San Francisco , California
| | - Alessandro Maggi
- 3 California Institute of Technology , Department of Medical Engineering, Pasadena, California
| | - Bianca Flores
- 1 UCSF Department of Bioengineering and Therapeutic Sciences, San Francisco , California
| | - Julia R Greer
- 4 California Institute of Technology, Division of Engineering and Applied Science, Kavli Nanoscience Institute , Pasadena, California
| | - Tejal Desai
- 1 UCSF Department of Bioengineering and Therapeutic Sciences, San Francisco , California
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38
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Sheikh Z, Brooks PJ, Barzilay O, Fine N, Glogauer M. Macrophages, Foreign Body Giant Cells and Their Response to Implantable Biomaterials. MATERIALS (BASEL, SWITZERLAND) 2015; 8:5671-5701. [PMID: 28793529 PMCID: PMC5512621 DOI: 10.3390/ma8095269] [Citation(s) in RCA: 455] [Impact Index Per Article: 45.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/03/2015] [Revised: 08/20/2015] [Accepted: 08/21/2015] [Indexed: 12/23/2022]
Abstract
All biomaterials, when implanted in vivo, elicit cellular and tissue responses. These responses include the inflammatory and wound healing responses, foreign body reactions, and fibrous encapsulation of the implanted materials. Macrophages are myeloid immune cells that are tactically situated throughout the tissues, where they ingest and degrade dead cells and foreign materials in addition to orchestrating inflammatory processes. Macrophages and their fused morphologic variants, the multinucleated giant cells, which include the foreign body giant cells (FBGCs) are the dominant early responders to biomaterial implantation and remain at biomaterial-tissue interfaces for the lifetime of the device. An essential aspect of macrophage function in the body is to mediate degradation of bio-resorbable materials including bone through extracellular degradation and phagocytosis. Biomaterial surface properties play a crucial role in modulating the foreign body reaction in the first couple of weeks following implantation. The foreign body reaction may impact biocompatibility of implantation devices and may considerably impact short- and long-term success in tissue engineering and regenerative medicine, necessitating a clear understanding of the foreign body reaction to different implantation materials. The focus of this review article is on the interactions of macrophages and foreign body giant cells with biomaterial surfaces, and the physical, chemical and morphological characteristics of biomaterial surfaces that play a role in regulating the foreign body response. Events in the foreign body response include protein adsorption, adhesion of monocytes/macrophages, fusion to form FBGCs, and the consequent modification of the biomaterial surface. The effect of physico-chemical cues on macrophages is not well known and there is a complex interplay between biomaterial properties and those that result from interactions with the local environment. By having a better understanding of the role of macrophages in the tissue healing processes, especially in events that follow biomaterial implantation, we can design novel biomaterials-based tissue-engineered constructs that elicit a favorable immune response upon implantation and perform for their intended applications.
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Affiliation(s)
- Zeeshan Sheikh
- Faculty of Dentistry, Matrix Dynamics Group, University of Toronto, 150 College Street, Toronto, ON M5S 3E2, Canada.
| | - Patricia J Brooks
- Faculty of Dentistry, Matrix Dynamics Group, University of Toronto, 150 College Street, Toronto, ON M5S 3E2, Canada.
| | - Oriyah Barzilay
- Faculty of Dentistry, Matrix Dynamics Group, University of Toronto, 150 College Street, Toronto, ON M5S 3E2, Canada.
| | - Noah Fine
- Faculty of Dentistry, Matrix Dynamics Group, University of Toronto, 150 College Street, Toronto, ON M5S 3E2, Canada.
| | - Michael Glogauer
- Faculty of Dentistry, Matrix Dynamics Group, University of Toronto, 150 College Street, Toronto, ON M5S 3E2, Canada.
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39
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Stem cell behavior on tailored porous oxide surface coatings. Biomaterials 2015; 55:96-109. [DOI: 10.1016/j.biomaterials.2015.03.033] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2014] [Revised: 03/16/2015] [Accepted: 03/20/2015] [Indexed: 01/01/2023]
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40
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Shao J, Chen S, Du C. Citric acid modification of PLLA nano-fibrous scaffolds to enhance cellular adhesion, proliferation and osteogenic differentiation. J Mater Chem B 2015; 3:5291-5299. [PMID: 32262605 DOI: 10.1039/c5tb00535c] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Citric acid (CA) was used in a thermally induced phase separation (TIPS) process to improve the surface hydrophilicity and cell affinity of PLLA nano-fibrous scaffolds. The evolution of architecture, structure and physicochemical properties of the scaffold after modification has been investigated. Cell viability, adhesion, proliferation and osteogenic differentiation were characterized to evaluate the cytocompatibility and biological properties of PLLA nano-fibrous scaffolds. Citric acid interacted with PLLA through hydrogen bond association and the introduction of strong polar groups (-COOH) on the PLLA surface improved its hydrophilicity with the contact angle decreasing to a suitable range for cell adhesion and spreading. The cell exhibited extensive spreading on the CA modified PLLA scaffolds with many cellular protrusions interacting with nanofibers. Furthermore, such a modification significantly increased the cell proliferation rate, enhanced the alkaline phosphatase (ALP) activity and bone-related gene expression (ALP, OCN, COL I and Runx2) of mBMSCs along with cell development. The results demonstrate a promising modification method to promote applications of PLLA-based scaffolds.
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Affiliation(s)
- Jundong Shao
- School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641, PR China
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41
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Khattak M, Pu F, Curran JM, Hunt JA, D'Sa RA. Human mesenchymal stem cell response to poly(ε-caprolactone/poly(methyl methacrylate) demixed thin films. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2015; 26:178. [PMID: 25893385 DOI: 10.1007/s10856-015-5507-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/13/2014] [Accepted: 03/30/2015] [Indexed: 06/04/2023]
Abstract
Advances in material sciences have enabled the fabrication of biomaterials which are able to provide the requisite cues to stimulate cells to behave in a specific way. Nanoscale surface topographies are well known to be able to positively influence cell-substrate interactions. This study reports on a novel series of poly(ε-caprolactone) PCL and poly(methyl methacrylate) demixed nanotopographic films as non-biological cell-stimulating cues. The topographic features observed ranged from nanoislands to nanopits. PMMA was observed to segregate to the air interface, while PCL preferred the substrate interface. Preliminary response of human mesenchymal stem cells to these surfaces indicated that the substrate with nanoisland topography has the potential to differentiate to osteogenic, chondrogenic and adipogenic lineages.
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Affiliation(s)
- Mohammed Khattak
- Centre for Materials and Structures, University of Liverpool, Brownlow Hill, Liverpool, L69 3GH, UK
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42
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Hsu HT, Rau LR, Zeng YN, Kang YL, Tsai SW, Wu MH. External vibration enhances macromolecular crowding for construction of aligned three-dimensional collagen fibril scaffolds. Biofabrication 2015; 7:025004. [DOI: 10.1088/1758-5090/7/2/025004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
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43
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Salmasi S, Kalaskar DM, Yoon WW, Blunn GW, Seifalian AM. Role of nanotopography in the development of tissue engineered 3D organs and tissues using mesenchymal stem cells. World J Stem Cells 2015; 7:266-80. [PMID: 25815114 PMCID: PMC4369486 DOI: 10.4252/wjsc.v7.i2.266] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2014] [Revised: 11/07/2014] [Accepted: 12/03/2014] [Indexed: 02/06/2023] Open
Abstract
Recent regenerative medicine and tissue engineering strategies (using cells, scaffolds, medical devices and gene therapy) have led to fascinating progress of translation of basic research towards clinical applications. In the past decade, great deal of research has focused on developing various three dimensional (3D) organs, such as bone, skin, liver, kidney and ear, using such strategies in order to replace or regenerate damaged organs for the purpose of maintaining or restoring organs' functions that may have been lost due to aging, accident or disease. The surface properties of a material or a device are key aspects in determining the success of the implant in biomedicine, as the majority of biological reactions in human body occur on surfaces or interfaces. Furthermore, it has been established in the literature that cell adhesion and proliferation are, to a great extent, influenced by the micro- and nano-surface characteristics of biomaterials and devices. In addition, it has been shown that the functions of stem cells, mesenchymal stem cells in particular, could be regulated through physical interaction with specific nanotopographical cues. Therefore, guided stem cell proliferation, differentiation and function are of great importance in the regeneration of 3D tissues and organs using tissue engineering strategies. This review will provide an update on the impact of nanotopography on mesenchymal stem cells for the purpose of developing laboratory-based 3D organs and tissues, as well as the most recent research and case studies on this topic.
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Affiliation(s)
- Shima Salmasi
- Shima Salmasi, Deepak M Kalaskar, Alexander M Seifalian, UCL Division of Surgery and Interventional Science, Centre for Nanotechnology and Regenerative Medicine, University College London, NW3 2PF London, United Kingdom
| | - Deepak M Kalaskar
- Shima Salmasi, Deepak M Kalaskar, Alexander M Seifalian, UCL Division of Surgery and Interventional Science, Centre for Nanotechnology and Regenerative Medicine, University College London, NW3 2PF London, United Kingdom
| | - Wai-Weng Yoon
- Shima Salmasi, Deepak M Kalaskar, Alexander M Seifalian, UCL Division of Surgery and Interventional Science, Centre for Nanotechnology and Regenerative Medicine, University College London, NW3 2PF London, United Kingdom
| | - Gordon W Blunn
- Shima Salmasi, Deepak M Kalaskar, Alexander M Seifalian, UCL Division of Surgery and Interventional Science, Centre for Nanotechnology and Regenerative Medicine, University College London, NW3 2PF London, United Kingdom
| | - Alexander M Seifalian
- Shima Salmasi, Deepak M Kalaskar, Alexander M Seifalian, UCL Division of Surgery and Interventional Science, Centre for Nanotechnology and Regenerative Medicine, University College London, NW3 2PF London, United Kingdom
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44
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Cheng D, Cao X, Gao H, Hou J, Li W, Hao L, Wang Y. Engineering poly(lactic-co-glycolic acid)/hydroxyapatite microspheres with diverse macropores patterns and the cellular responses. RSC Adv 2015. [DOI: 10.1039/c4ra15561k] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Design macroporous topography on spherical substrates via a straightforward approach and investigate the corresponding cell responses.
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Affiliation(s)
- D. Cheng
- School of Materials Science and Engineering
- South China University of Technology
- Guangzhou 510641
- China
- National Engineering Research Center for Tissue Restoration and Reconstruction
| | - X. Cao
- School of Materials Science and Engineering
- South China University of Technology
- Guangzhou 510641
- China
- National Engineering Research Center for Tissue Restoration and Reconstruction
| | - H. Gao
- School of Materials Science and Engineering
- South China University of Technology
- Guangzhou 510641
- China
- National Engineering Research Center for Tissue Restoration and Reconstruction
| | - J. Hou
- School of Materials Science and Engineering
- South China University of Technology
- Guangzhou 510641
- China
- National Engineering Research Center for Tissue Restoration and Reconstruction
| | - W. Li
- School of Materials Science and Engineering
- South China University of Technology
- Guangzhou 510641
- China
- National Engineering Research Center for Tissue Restoration and Reconstruction
| | - L. Hao
- School of Materials Science and Engineering
- South China University of Technology
- Guangzhou 510641
- China
- National Engineering Research Center for Tissue Restoration and Reconstruction
| | - Y. Wang
- School of Materials Science and Engineering
- South China University of Technology
- Guangzhou 510641
- China
- National Engineering Research Center for Tissue Restoration and Reconstruction
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45
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Walters NJ, Gentleman E. Evolving insights in cell-matrix interactions: elucidating how non-soluble properties of the extracellular niche direct stem cell fate. Acta Biomater 2015; 11:3-16. [PMID: 25266503 PMCID: PMC5833939 DOI: 10.1016/j.actbio.2014.09.038] [Citation(s) in RCA: 108] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2014] [Revised: 08/22/2014] [Accepted: 09/22/2014] [Indexed: 12/26/2022]
Abstract
The role of soluble messengers in directing cellular behaviours has been recognized for decades. However, many cellular processes, including adhesion, migration and stem cell differentiation, are also governed by chemical and physical interactions with non-soluble components of the extracellular matrix (ECM). Among other effects, a cell's perception of nanoscale features such as substrate topography and ligand presentation, and its ability to deform the matrix via the generation of cytoskeletal tension play fundamental roles in these cellular processes. As a result, many biomaterials-based tissue engineering and regenerative medicine strategies aim to harness the cell's perception of substrate stiffness and nanoscale features to direct particular behaviours. However, since cell-ECM interactions vary considerably between two-dimensional (2-D) and three-dimensional (3-D) models, understanding their influence over normal and pathological cell responses in 3-D systems that better mimic the in vivo microenvironment is essential to translate such insights efficiently into medical therapies. This review summarizes the key findings in these areas and discusses how insights from 2-D biomaterials are being used to examine cellular behaviours in more complex 3-D hydrogel systems, in which not only matrix stiffness, but also degradability, plays an important role, and in which defining the nanoscale ligand presentation presents an additional challenge.
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Affiliation(s)
- Nick J Walters
- Division of Biomaterials & Tissue Engineering, UCL Eastman Dental Institute, London WC1X 8LD, UK
| | - Eileen Gentleman
- Craniofacial Development & Stem Cell Biology, King's College London, London SE1 9RT, UK.
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46
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Jeong EJ, Lee JW, Kwark YJ, Kim SH, Lee KY. The height of cell-adhesive nanoposts generated by block copolymer/surfactant complex systems influences the preosteoblast phenotype. Colloids Surf B Biointerfaces 2014; 123:679-84. [PMID: 25456988 DOI: 10.1016/j.colsurfb.2014.10.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2014] [Revised: 09/25/2014] [Accepted: 10/04/2014] [Indexed: 10/24/2022]
Abstract
In tissue engineering, the nanoscale topography of the substrate is important, because transplanted cells can recognize and respond to topographical patterns, allowing control of gene expression and tissue formation. In this study, we hypothesized that the height of cell-adhesive nanoposts could regulate cell phenotype. Nano-patterned surfaces were generated via self-assembly of polystyrene-b-poly(ethylene oxide)/dodecylbenzenesulfonic acid (PS-b-PEO/DBSA) complex systems. The height of PS nanoposts, which are considered to be cell-adhesion domains, was varied from 11 to 43 nm, while nanopost size and the center-to-center distance between nanoposts were kept constant. Adhesion, growth, and differentiation of mouse preosteoblasts (MC3T3-E1) cultured on the nano-patterned surfaces were significantly influenced by nanopost height. This approach therefore holds great promise for the design of biomedical devices, as well as tissue engineering scaffolds.
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Affiliation(s)
- Eun Ju Jeong
- Department of Bioengineering, Hanyang University, Seoul 133-791, Republic of Korea
| | - Jin Wook Lee
- Department of Applied Organic Materials, Inha University, Incheon 402-751, Republic of Korea
| | - Young-Je Kwark
- Department of Organic Materials and Fiber Engineering, Soongsil University, Seoul 156-743, Republic of Korea
| | - Seung Hyun Kim
- Department of Applied Organic Materials, Inha University, Incheon 402-751, Republic of Korea.
| | - Kuen Yong Lee
- Department of Bioengineering, Hanyang University, Seoul 133-791, Republic of Korea.
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47
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Prittinen J, Jiang Y, Ylärinne JH, Pakkanen TA, Lammi MJ, Qu C. Chondrocyte behavior on nanostructured micropillar polypropylene and polystyrene surfaces. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2014; 43:424-31. [PMID: 25175232 DOI: 10.1016/j.msec.2014.07.045] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 04/17/2014] [Revised: 06/27/2014] [Accepted: 07/13/2014] [Indexed: 01/26/2023]
Abstract
This study was aimed to investigate whether patterned polypropylene (PP) or polystyrene (PS) could enhance the chondrocytes' extracellular matrix (ECM) production and phenotype maintenance. Bovine primary chondrocytes were cultured on smooth PP and PS, as well as on nanostructured micropillar PP (patterned PP) and PS (patterned PS) for 2 weeks. Subsequently, the samples were collected for fluorescein diacetate-based cell viability tests, for immunocytochemical assays of types I and II collagen, actin and vinculin, for scanning electronic microscopic analysis of cell morphology and distribution, and for gene expression assays of Sox9, aggrecan, procollagen α1(II), procollagen α1(X), and procollagen α2(I) using quantitative RT-PCR assays. After two weeks of culture, the bovine primary chondrocytes had attached on both patterned PP and PS, while practically no adhesion was observed on smooth PP. However, the best adhesion of the cells was on smooth PS. The cells, which attached on patterned PP and PS surfaces synthesized types I and II collagen. The chondrocytes' morphology was extended, and an abundant ECM network formed around the attached chondrocytes on both patterned PP and PS. Upon passaging, no significant differences on the chondrocyte-specific gene expression were observed, although the highest expression level of aggrecan was observed on the patterned PS in passage 1 chondrocytes, and the expression level of procollagen α1(II) appeared to decrease in passaged chondrocytes. However, the expressions of procollagen α2(I) were increased in all passaged cell cultures. In conclusion, the bovine primary chondrocytes could be grown on patterned PS and PP surfaces, and they produced extracellular matrix network around the adhered cells. However, neither the patterned PS nor PP could prevent the dedifferentiation of chondrocytes.
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Affiliation(s)
- Juha Prittinen
- Department of Applied Physics, University of Eastern Finland, Kuopio, Finland
| | - Yu Jiang
- Department of Chemistry, University of Eastern Finland, Joensuu, Finland
| | - Janne H Ylärinne
- Department of Applied Physics, University of Eastern Finland, Kuopio, Finland
| | - Tapani A Pakkanen
- Department of Chemistry, University of Eastern Finland, Joensuu, Finland
| | - Mikko J Lammi
- Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
| | - Chengjuan Qu
- Department of Applied Physics, University of Eastern Finland, Kuopio, Finland
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48
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Balasundaram G, Storey DM, Webster TJ. Novel nano-rough polymers for cartilage tissue engineering. Int J Nanomedicine 2014; 9:1845-53. [PMID: 24790427 PMCID: PMC3998868 DOI: 10.2147/ijn.s55865] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
This study presents an innovative method for creating a highly porous surface with nanoscale roughness on biologically relevant polymers, specifically polyurethane (PU) and polycaprolactone (PCL). Nanoembossed polyurethane (NPU) and nanoembossed polycaprolactone (NPCL) were produced by the casting of PU and PCL over a plasma-deposited, spiky nanofeatured crystalline titanium (Ti) surface. The variables used in the process of making the spiky Ti surface can be altered to change the physical properties of the spiky particles, and thus, the cast polymer substrate surface can be altered. The spiky Ti surface is reusable to produce additional nanopolymer castings. In this study, control plain PU and PCL polymers were produced by casting the polymers over a plain Ti surface (without spikes). All polymer surface morphologies were characterized using both scanning electron microscopy and atomic force microscopy, and their surface energies were measured using liquid contact angle measurements. The results revealed that both NPU and NPCL possessed a higher degree of nanometer surface roughness and higher surface energy compared with their respective unaltered polymers. Further, an in vitro study was carried out to determine chondrocyte (cartilage-producing cells) functions on NPU and NPCL compared with on control plain polymers. Results of this study provided evidence of increased chondrocyte numbers on NPU and NPCL compared with their respective plain polymers after periods of up to 7 days. Moreover, the results provide evidence of greater intracellular protein production and collagen secretion by chondrocytes cultured on NPU and NPCL compared with control plain polymers. In summary, the present in vitro results of increased chondrocyte functions on NPU and NPCL suggest these materials may be suitable for numerous polymer-based cartilage tissue-engineering applications and, thus, deserve further investigation.
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Affiliation(s)
| | | | - Thomas J Webster
- Department of Chemical Engineering, Northeastern University, Boston, MA, USA ; Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia
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49
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Labarge MA, Parvin B, Lorens JB. Molecular deconstruction, detection, and computational prediction of microenvironment-modulated cellular responses to cancer therapeutics. Adv Drug Deliv Rev 2014; 69-70:123-31. [PMID: 24582543 DOI: 10.1016/j.addr.2014.02.009] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2013] [Revised: 02/14/2014] [Accepted: 02/18/2014] [Indexed: 12/21/2022]
Abstract
The field of bioengineering has pioneered the application of new precision fabrication technologies to model the different geometric, physical or molecular components of tissue microenvironments on solid-state substrata. Tissue engineering approaches building on these advances are used to assemble multicellular mimetic-tissues where cells reside within defined spatial contexts. The functional responses of cells in fabricated microenvironments have revealed a rich interplay between the genome and extracellular effectors in determining cellular phenotypes and in a number of cases have revealed the dominance of microenvironment over genotype. Precision bioengineered substrata are limited to a few aspects, whereas cell/tissue-derived microenvironments have many undefined components. Thus, introducing a computational module may serve to integrate these types of platforms to create reasonable models of drug responses in human tissues. This review discusses how combinatorial microenvironment microarrays and other biomimetic microenvironments have revealed emergent properties of cells in particular microenvironmental contexts, the platforms that can measure phenotypic changes within those contexts, and the computational tools that can unify the microenvironment-imposed functional phenotypes with underlying constellations of proteins and genes. Ultimately we propose that a merger of these technologies will enable more accurate pre-clinical drug discovery.
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Affiliation(s)
- Mark A Labarge
- Life Science Division of Lawrence Berkeley National Laboratory, University of California, 1 Cylcotron Rd, MS977, Berkeley, CA 94720, USA.
| | - Bahram Parvin
- Life Science Division of Lawrence Berkeley National Laboratory, University of California, 1 Cylcotron Rd, MS977, Berkeley, CA 94720, USA.
| | - James B Lorens
- Department of Biomedicine and Center for Cancer Biomarkers, University of Bergen, Jonas Lies vei 91, NO-5020 Bergen, Norway.
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Jeon H, Simon CG, Kim G. A mini-review: Cell response to microscale, nanoscale, and hierarchical patterning of surface structure. J Biomed Mater Res B Appl Biomater 2014; 102:1580-94. [DOI: 10.1002/jbm.b.33158] [Citation(s) in RCA: 112] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2013] [Revised: 03/04/2014] [Accepted: 03/13/2014] [Indexed: 12/17/2022]
Affiliation(s)
- HoJun Jeon
- Department of Bio-Mechatronic Engineering; College of Biotechnology and Bioengineering, Sungkyunkwan University; Suwon South Korea
| | - Carl G. Simon
- Biosystems and Biomaterials Division; National Institute of Standards and Technology; Gaithersburg Maryland
| | - GeunHyung Kim
- Department of Bio-Mechatronic Engineering; College of Biotechnology and Bioengineering, Sungkyunkwan University; Suwon South Korea
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