Methacrylated Cartilage ECM-Based Hydrogels as Injectables and Bioinks for Cartilage Tissue Engineering

Articular cartilage (AC) possesses a limited healing potential, meaning that untreated focal joint defects typically progress, leading to the development of degenerative diseases such as osteoarthritis. Several clinical strategies exist that aim to regenerate AC; however, recapitulation of a fully f...

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Main Authors: Kevin Behan, Alexandre Dufour, Orquidea Garcia, Daniel Kelly
Format: Article
Language:English
Published: MDPI AG 2022-01-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/12/2/216
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author Kevin Behan
Alexandre Dufour
Orquidea Garcia
Daniel Kelly
author_facet Kevin Behan
Alexandre Dufour
Orquidea Garcia
Daniel Kelly
author_sort Kevin Behan
collection DOAJ
description Articular cartilage (AC) possesses a limited healing potential, meaning that untreated focal joint defects typically progress, leading to the development of degenerative diseases such as osteoarthritis. Several clinical strategies exist that aim to regenerate AC; however, recapitulation of a fully functional, load-bearing tissue remains a significant challenge. This can be attributed, at least in part, to a paucity of biomaterials that truly mimic the native tissue and provide appropriate cues to direct its regeneration. The main structural component of articular cartilage, type II collagen, does not readily gelate at body temperature, challenging the development of cartilage extracellular matrix (cECM)-derived injectable hydrogels and bioinks for AC tissue engineering and bioprinting applications. Here, we describe the development and rheological characterisation of a methacrylated cartilage ECM-based hydrogel/bioink (cECM-MA), which could be photocrosslinked when exposed to ultraviolet (UV) light. Functionalisation of the collagen backbone with methacryloyl groups had a negligible effect on triple helix stability, as demonstrated by circular dichroism spectroscopy. These cECM-MA bioinks demonstrated shear-thinning properties and could be loaded with bone marrow mesenchymal stem cells (BM-MSCs), micro-extruded to generate self-supporting 3D constructs of predefined size and shape, and then photocrosslinked using UV light. Analysis of the cell-laden constructs showed that the BM-MSCs were viable post-printing and underwent chondrogenesis in vitro, generating a tissue rich in sulphated glycosaminoglycans and collagens. These results support the use of methacrylated, tissue-specific ECM-derived hydrogels as bioinks for 3D bioprinting and/or as injectables for cartilage tissue engineering applications.
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spelling doaj.art-c2afad2a4fff4f569be6e2df328cd4832023-11-23T18:58:22ZengMDPI AGBiomolecules2218-273X2022-01-0112221610.3390/biom12020216Methacrylated Cartilage ECM-Based Hydrogels as Injectables and Bioinks for Cartilage Tissue EngineeringKevin Behan0Alexandre Dufour1Orquidea Garcia2Daniel Kelly3Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02 PN40 Dublin, IrelandTrinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02 PN40 Dublin, IrelandJohnson & Johnson Services, Inc., 31 Technology Drive, Irvine, CA 92618, USATrinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02 PN40 Dublin, IrelandArticular cartilage (AC) possesses a limited healing potential, meaning that untreated focal joint defects typically progress, leading to the development of degenerative diseases such as osteoarthritis. Several clinical strategies exist that aim to regenerate AC; however, recapitulation of a fully functional, load-bearing tissue remains a significant challenge. This can be attributed, at least in part, to a paucity of biomaterials that truly mimic the native tissue and provide appropriate cues to direct its regeneration. The main structural component of articular cartilage, type II collagen, does not readily gelate at body temperature, challenging the development of cartilage extracellular matrix (cECM)-derived injectable hydrogels and bioinks for AC tissue engineering and bioprinting applications. Here, we describe the development and rheological characterisation of a methacrylated cartilage ECM-based hydrogel/bioink (cECM-MA), which could be photocrosslinked when exposed to ultraviolet (UV) light. Functionalisation of the collagen backbone with methacryloyl groups had a negligible effect on triple helix stability, as demonstrated by circular dichroism spectroscopy. These cECM-MA bioinks demonstrated shear-thinning properties and could be loaded with bone marrow mesenchymal stem cells (BM-MSCs), micro-extruded to generate self-supporting 3D constructs of predefined size and shape, and then photocrosslinked using UV light. Analysis of the cell-laden constructs showed that the BM-MSCs were viable post-printing and underwent chondrogenesis in vitro, generating a tissue rich in sulphated glycosaminoglycans and collagens. These results support the use of methacrylated, tissue-specific ECM-derived hydrogels as bioinks for 3D bioprinting and/or as injectables for cartilage tissue engineering applications.https://www.mdpi.com/2218-273X/12/2/216bioinkscartilagebioprinting
spellingShingle Kevin Behan
Alexandre Dufour
Orquidea Garcia
Daniel Kelly
Methacrylated Cartilage ECM-Based Hydrogels as Injectables and Bioinks for Cartilage Tissue Engineering
Biomolecules
bioinks
cartilage
bioprinting
title Methacrylated Cartilage ECM-Based Hydrogels as Injectables and Bioinks for Cartilage Tissue Engineering
title_full Methacrylated Cartilage ECM-Based Hydrogels as Injectables and Bioinks for Cartilage Tissue Engineering
title_fullStr Methacrylated Cartilage ECM-Based Hydrogels as Injectables and Bioinks for Cartilage Tissue Engineering
title_full_unstemmed Methacrylated Cartilage ECM-Based Hydrogels as Injectables and Bioinks for Cartilage Tissue Engineering
title_short Methacrylated Cartilage ECM-Based Hydrogels as Injectables and Bioinks for Cartilage Tissue Engineering
title_sort methacrylated cartilage ecm based hydrogels as injectables and bioinks for cartilage tissue engineering
topic bioinks
cartilage
bioprinting
url https://www.mdpi.com/2218-273X/12/2/216
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AT orquideagarcia methacrylatedcartilageecmbasedhydrogelsasinjectablesandbioinksforcartilagetissueengineering
AT danielkelly methacrylatedcartilageecmbasedhydrogelsasinjectablesandbioinksforcartilagetissueengineering