The bio in the ink: cartilage regeneration with bioprintable hydrogels and articular cartilage-derived progenitor cells

[Display omitted] Cell-laden hydrogels are the primary building blocks for bioprinting, and, also termed bioinks, are the foundations for creating structures that can potentially recapitulate the architecture of articular cartilage. To be functional, hydrogel constructs need to unlock the regenerati...

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Veröffentlicht in:Acta biomaterialia 2017-10, Vol.61, p.41-53
Hauptverfasser: Levato, Riccardo, Webb, William R., Otto, Iris A., Mensinga, Anneloes, Zhang, Yadan, van Rijen, Mattie, van Weeren, René, Khan, Ilyas M., Malda, Jos
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container_end_page 53
container_issue
container_start_page 41
container_title Acta biomaterialia
container_volume 61
creator Levato, Riccardo
Webb, William R.
Otto, Iris A.
Mensinga, Anneloes
Zhang, Yadan
van Rijen, Mattie
van Weeren, René
Khan, Ilyas M.
Malda, Jos
description [Display omitted] Cell-laden hydrogels are the primary building blocks for bioprinting, and, also termed bioinks, are the foundations for creating structures that can potentially recapitulate the architecture of articular cartilage. To be functional, hydrogel constructs need to unlock the regenerative capacity of encapsulated cells. The recent identification of multipotent articular cartilage-resident chondroprogenitor cells (ACPCs), which share important traits with adult stem cells, represents a new opportunity for cartilage regeneration. However, little is known about the suitability of ACPCs for tissue engineering, especially in combination with biomaterials. This study aimed to investigate the potential of ACPCs in hydrogels for cartilage regeneration and biofabrication, and to evaluate their ability for zone-specific matrix production. Gelatin methacryloyl (gelMA)-based hydrogels were used to culture ACPCs, bone marrow mesenchymal stromal cells (MSCs) and chondrocytes, and as bioinks for printing. Our data shows ACPCs outperformed chondrocytes in terms of neo-cartilage production and unlike MSCs, ACPCs had the lowest gene expression levels of hypertrophy marker collagen type X, and the highest expression of PRG4, a key factor in joint lubrication. Co-cultures of the cell types in multi-compartment hydrogels allowed generating constructs with a layered distribution of collagens and glycosaminoglycans. By combining ACPC- and MSC-laden bioinks, a bioprinted model of articular cartilage was generated, consisting of defined superficial and deep regions, each with distinct cellular and extracellular matrix composition. Taken together, these results provide important information for the use of ACPC-laden hydrogels in regenerative medicine, and pave the way to the biofabrication of 3D constructs with multiple cell types for cartilage regeneration or in vitro tissue models. Despite its limited ability to repair, articular cartilage harbors an endogenous population of progenitor cells (ACPCs), that to date, received limited attention in biomaterials and tissue engineering applications. Harnessing the potential of these cells in 3D hydrogels can open new avenues for biomaterial-based regenerative therapies, especially with advanced biofabrication technologies (e.g. bioprinting). This study highlights the potential of ACPCs to generate neo-cartilage in a gelatin-based hydrogel and bioink. The ACPC-laden hydrogel is a suitable substrate for chondrogenesis and dat
doi_str_mv 10.1016/j.actbio.2017.08.005
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To be functional, hydrogel constructs need to unlock the regenerative capacity of encapsulated cells. The recent identification of multipotent articular cartilage-resident chondroprogenitor cells (ACPCs), which share important traits with adult stem cells, represents a new opportunity for cartilage regeneration. However, little is known about the suitability of ACPCs for tissue engineering, especially in combination with biomaterials. This study aimed to investigate the potential of ACPCs in hydrogels for cartilage regeneration and biofabrication, and to evaluate their ability for zone-specific matrix production. Gelatin methacryloyl (gelMA)-based hydrogels were used to culture ACPCs, bone marrow mesenchymal stromal cells (MSCs) and chondrocytes, and as bioinks for printing. Our data shows ACPCs outperformed chondrocytes in terms of neo-cartilage production and unlike MSCs, ACPCs had the lowest gene expression levels of hypertrophy marker collagen type X, and the highest expression of PRG4, a key factor in joint lubrication. Co-cultures of the cell types in multi-compartment hydrogels allowed generating constructs with a layered distribution of collagens and glycosaminoglycans. By combining ACPC- and MSC-laden bioinks, a bioprinted model of articular cartilage was generated, consisting of defined superficial and deep regions, each with distinct cellular and extracellular matrix composition. Taken together, these results provide important information for the use of ACPC-laden hydrogels in regenerative medicine, and pave the way to the biofabrication of 3D constructs with multiple cell types for cartilage regeneration or in vitro tissue models. Despite its limited ability to repair, articular cartilage harbors an endogenous population of progenitor cells (ACPCs), that to date, received limited attention in biomaterials and tissue engineering applications. Harnessing the potential of these cells in 3D hydrogels can open new avenues for biomaterial-based regenerative therapies, especially with advanced biofabrication technologies (e.g. bioprinting). This study highlights the potential of ACPCs to generate neo-cartilage in a gelatin-based hydrogel and bioink. The ACPC-laden hydrogel is a suitable substrate for chondrogenesis and data shows it has a bias in directing cells towards a superficial zone phenotype. For the first time, ACPC-hydrogels are evaluated both as alternative for and in combination with chondrocytes and MSCs, using co-cultures and bioprinting for cartilage regeneration in vitro. This study provides important cues on ACPCs, indicating they represent a promising cell source for the next generation of cartilage constructs with increased biomimicry.</description><identifier>ISSN: 1742-7061</identifier><identifier>EISSN: 1878-7568</identifier><identifier>DOI: 10.1016/j.actbio.2017.08.005</identifier><identifier>PMID: 28782725</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Bioengineering ; Biofabrication ; Biomarkers - metabolism ; Biomaterials ; Biomedical materials ; Bioprinting - methods ; Bone marrow ; Cartilage ; Cartilage (articular) ; Cartilage regeneration ; Cartilage, Articular - cytology ; Cell culture ; Cell Differentiation - drug effects ; Cell Differentiation - genetics ; Cells (biology) ; Cells, Cultured ; Chondrocytes ; Chondrogenesis - drug effects ; Chondrogenesis - genetics ; Chondroprogenitor cells ; Co-culture ; Coculture Techniques ; Collagen ; Compressive Strength ; DNA - metabolism ; Extracellular matrix ; Gelatin ; Gene expression ; Glycosaminoglycans ; Glycosaminoglycans - metabolism ; Horses ; Hydrogel ; Hydrogel, Polyethylene Glycol Dimethacrylate - pharmacology ; Hydrogels ; Hydrogels - pharmacology ; Hypertrophy ; Ink ; Lubrication ; Mesenchymal Stem Cells - cytology ; Mesenchymal Stem Cells - drug effects ; Mesenchymal Stem Cells - metabolism ; Mesenchyme ; Printing ; Regeneration (physiology) ; Regeneration - drug effects ; Regenerative medicine ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Stem cells ; Stem Cells - cytology ; Stem Cells - drug effects ; Stromal cells ; Sus scrofa ; Three dimensional printing ; Tissue engineering</subject><ispartof>Acta biomaterialia, 2017-10, Vol.61, p.41-53</ispartof><rights>2017 Acta Materialia Inc.</rights><rights>Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. 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Despite its limited ability to repair, articular cartilage harbors an endogenous population of progenitor cells (ACPCs), that to date, received limited attention in biomaterials and tissue engineering applications. Harnessing the potential of these cells in 3D hydrogels can open new avenues for biomaterial-based regenerative therapies, especially with advanced biofabrication technologies (e.g. bioprinting). This study highlights the potential of ACPCs to generate neo-cartilage in a gelatin-based hydrogel and bioink. The ACPC-laden hydrogel is a suitable substrate for chondrogenesis and data shows it has a bias in directing cells towards a superficial zone phenotype. For the first time, ACPC-hydrogels are evaluated both as alternative for and in combination with chondrocytes and MSCs, using co-cultures and bioprinting for cartilage regeneration in vitro. 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Webb, William R. ; Otto, Iris A. ; Mensinga, Anneloes ; Zhang, Yadan ; van Rijen, Mattie ; van Weeren, René ; Khan, Ilyas M. ; Malda, Jos</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c600t-be7685648166349da759705427ad3271cc70af32c13601995992cf7e3c27cfab3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Bioengineering</topic><topic>Biofabrication</topic><topic>Biomarkers - metabolism</topic><topic>Biomaterials</topic><topic>Biomedical materials</topic><topic>Bioprinting - methods</topic><topic>Bone marrow</topic><topic>Cartilage</topic><topic>Cartilage (articular)</topic><topic>Cartilage regeneration</topic><topic>Cartilage, Articular - cytology</topic><topic>Cell culture</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Differentiation - genetics</topic><topic>Cells (biology)</topic><topic>Cells, Cultured</topic><topic>Chondrocytes</topic><topic>Chondrogenesis - drug effects</topic><topic>Chondrogenesis - genetics</topic><topic>Chondroprogenitor cells</topic><topic>Co-culture</topic><topic>Coculture Techniques</topic><topic>Collagen</topic><topic>Compressive Strength</topic><topic>DNA - metabolism</topic><topic>Extracellular matrix</topic><topic>Gelatin</topic><topic>Gene expression</topic><topic>Glycosaminoglycans</topic><topic>Glycosaminoglycans - metabolism</topic><topic>Horses</topic><topic>Hydrogel</topic><topic>Hydrogel, Polyethylene Glycol Dimethacrylate - pharmacology</topic><topic>Hydrogels</topic><topic>Hydrogels - pharmacology</topic><topic>Hypertrophy</topic><topic>Ink</topic><topic>Lubrication</topic><topic>Mesenchymal Stem Cells - cytology</topic><topic>Mesenchymal Stem Cells - drug effects</topic><topic>Mesenchymal Stem Cells - metabolism</topic><topic>Mesenchyme</topic><topic>Printing</topic><topic>Regeneration (physiology)</topic><topic>Regeneration - drug effects</topic><topic>Regenerative medicine</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Stem cells</topic><topic>Stem Cells - cytology</topic><topic>Stem Cells - drug effects</topic><topic>Stromal cells</topic><topic>Sus scrofa</topic><topic>Three dimensional printing</topic><topic>Tissue engineering</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Levato, Riccardo</creatorcontrib><creatorcontrib>Webb, William R.</creatorcontrib><creatorcontrib>Otto, Iris A.</creatorcontrib><creatorcontrib>Mensinga, Anneloes</creatorcontrib><creatorcontrib>Zhang, Yadan</creatorcontrib><creatorcontrib>van Rijen, Mattie</creatorcontrib><creatorcontrib>van Weeren, René</creatorcontrib><creatorcontrib>Khan, Ilyas M.</creatorcontrib><creatorcontrib>Malda, Jos</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Electronics &amp; 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To be functional, hydrogel constructs need to unlock the regenerative capacity of encapsulated cells. The recent identification of multipotent articular cartilage-resident chondroprogenitor cells (ACPCs), which share important traits with adult stem cells, represents a new opportunity for cartilage regeneration. However, little is known about the suitability of ACPCs for tissue engineering, especially in combination with biomaterials. This study aimed to investigate the potential of ACPCs in hydrogels for cartilage regeneration and biofabrication, and to evaluate their ability for zone-specific matrix production. Gelatin methacryloyl (gelMA)-based hydrogels were used to culture ACPCs, bone marrow mesenchymal stromal cells (MSCs) and chondrocytes, and as bioinks for printing. Our data shows ACPCs outperformed chondrocytes in terms of neo-cartilage production and unlike MSCs, ACPCs had the lowest gene expression levels of hypertrophy marker collagen type X, and the highest expression of PRG4, a key factor in joint lubrication. Co-cultures of the cell types in multi-compartment hydrogels allowed generating constructs with a layered distribution of collagens and glycosaminoglycans. By combining ACPC- and MSC-laden bioinks, a bioprinted model of articular cartilage was generated, consisting of defined superficial and deep regions, each with distinct cellular and extracellular matrix composition. Taken together, these results provide important information for the use of ACPC-laden hydrogels in regenerative medicine, and pave the way to the biofabrication of 3D constructs with multiple cell types for cartilage regeneration or in vitro tissue models. Despite its limited ability to repair, articular cartilage harbors an endogenous population of progenitor cells (ACPCs), that to date, received limited attention in biomaterials and tissue engineering applications. Harnessing the potential of these cells in 3D hydrogels can open new avenues for biomaterial-based regenerative therapies, especially with advanced biofabrication technologies (e.g. bioprinting). This study highlights the potential of ACPCs to generate neo-cartilage in a gelatin-based hydrogel and bioink. The ACPC-laden hydrogel is a suitable substrate for chondrogenesis and data shows it has a bias in directing cells towards a superficial zone phenotype. For the first time, ACPC-hydrogels are evaluated both as alternative for and in combination with chondrocytes and MSCs, using co-cultures and bioprinting for cartilage regeneration in vitro. This study provides important cues on ACPCs, indicating they represent a promising cell source for the next generation of cartilage constructs with increased biomimicry.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>28782725</pmid><doi>10.1016/j.actbio.2017.08.005</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1742-7061
ispartof Acta biomaterialia, 2017-10, Vol.61, p.41-53
issn 1742-7061
1878-7568
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7116023
source MEDLINE; ScienceDirect Journals (5 years ago - present)
subjects Animals
Bioengineering
Biofabrication
Biomarkers - metabolism
Biomaterials
Biomedical materials
Bioprinting - methods
Bone marrow
Cartilage
Cartilage (articular)
Cartilage regeneration
Cartilage, Articular - cytology
Cell culture
Cell Differentiation - drug effects
Cell Differentiation - genetics
Cells (biology)
Cells, Cultured
Chondrocytes
Chondrogenesis - drug effects
Chondrogenesis - genetics
Chondroprogenitor cells
Co-culture
Coculture Techniques
Collagen
Compressive Strength
DNA - metabolism
Extracellular matrix
Gelatin
Gene expression
Glycosaminoglycans
Glycosaminoglycans - metabolism
Horses
Hydrogel
Hydrogel, Polyethylene Glycol Dimethacrylate - pharmacology
Hydrogels
Hydrogels - pharmacology
Hypertrophy
Ink
Lubrication
Mesenchymal Stem Cells - cytology
Mesenchymal Stem Cells - drug effects
Mesenchymal Stem Cells - metabolism
Mesenchyme
Printing
Regeneration (physiology)
Regeneration - drug effects
Regenerative medicine
RNA, Messenger - genetics
RNA, Messenger - metabolism
Stem cells
Stem Cells - cytology
Stem Cells - drug effects
Stromal cells
Sus scrofa
Three dimensional printing
Tissue engineering
title The bio in the ink: cartilage regeneration with bioprintable hydrogels and articular cartilage-derived progenitor cells
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