3D bioprinting of methacrylated hyaluronic acid (MeHA) hydrogel with intrinsic osteogenicity

Michelle T. Poldervaart, Birgit Goversen, Mylène De Ruijter, Anna Abbadessa, Ferry Melchels, F. Cumhur Öner, Wouter J. A. Dhert, Tina Vermonden, Jacqueline Alblas

Research output: Contribution to journalArticle

Abstract

In bone regenerative medicine there is a need for suitable bone substitutes. Hydrogels have excellent biocompatible and biodegradable characteristics, but their visco-elastic properties limit their applicability, especially with respect to 3D bioprinting. In this study, we modified the naturally occurring extracellular matrix glycosaminoglycan hyaluronic acid (HA), in order to yield photo-crosslinkable hydrogels with increased mechanical stiffness and long-term stability, and with minimal decrease in cytocompatibility. Application of these tailor-made methacrylated hyaluronic acid (MeHA) gels for bone tissue engineering and 3D bioprinting was the subject of investigation. Visco-elastic properties of MeHA gels, measured by rheology and dynamic mechanical analysis, showed that irradiation of the hydrogels with UV light led to increased storage moduli and elastic moduli, indicating increasing gel rigidity. Subsequently, human bone marrow derived mesenchymal stromal cells (MSCs) were incorporated into MeHA hydrogels, and cell viability remained 64.4% after 21 days of culture. Osteogenic differentiation of MSCs occurred spontaneously in hydrogels with high concentrations of MeHA polymer, in absence of additional osteogenic stimuli. Addition of bone morphogenetic protein-2 (BMP-2) to the culture medium further increased osteogenic differentiation, as evidenced by increased matrix mineralisation. MeHA hydrogels demonstrated to be suitable for 3D bioprinting, and were printed into porous and anatomically shaped scaffolds. Taken together, photosensitive MeHA-based hydrogels fulfilled our criteria for cellular bioprinted bone constructs within a narrow window of concentration.
Original languageEnglish
Article numbere0177628
JournalPLOS ONE
Volume12
Issue number6
DOIs
StatePublished - 6 Jun 2017

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Bioprinting
Hydrogels
Hydrogel
Hyaluronic Acid
Hyaluronic acid
acids
acid
Bone
bone
bones
Gels
Bone and Bones
gels
gel
Mesenchymal Stromal Cells
Elastic moduli
elastic properties
matrices
elastic property
matrix

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Poldervaart, M. T., Goversen, B., De Ruijter, M., Abbadessa, A., Melchels, F., Öner, F. C., ... Alblas, J. (2017). 3D bioprinting of methacrylated hyaluronic acid (MeHA) hydrogel with intrinsic osteogenicity. PLOS ONE, 12(6), [e0177628]. DOI: 10.1371/journal.pone.0177628

Poldervaart, Michelle T.; Goversen, Birgit; De Ruijter, Mylène; Abbadessa, Anna; Melchels, Ferry; Öner, F. Cumhur; Dhert, Wouter J. A.; Vermonden, Tina; Alblas, Jacqueline / 3D bioprinting of methacrylated hyaluronic acid (MeHA) hydrogel with intrinsic osteogenicity.

In: PLOS ONE, Vol. 12, No. 6, e0177628, 06.06.2017.

Research output: Contribution to journalArticle

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Poldervaart, MT, Goversen, B, De Ruijter, M, Abbadessa, A, Melchels, F, Öner, FC, Dhert, WJA, Vermonden, T & Alblas, J 2017, '3D bioprinting of methacrylated hyaluronic acid (MeHA) hydrogel with intrinsic osteogenicity' PLOS ONE, vol 12, no. 6, e0177628. DOI: 10.1371/journal.pone.0177628

3D bioprinting of methacrylated hyaluronic acid (MeHA) hydrogel with intrinsic osteogenicity. / Poldervaart, Michelle T.; Goversen, Birgit; De Ruijter, Mylène; Abbadessa, Anna; Melchels, Ferry; Öner, F. Cumhur; Dhert, Wouter J. A.; Vermonden, Tina; Alblas, Jacqueline.

In: PLOS ONE, Vol. 12, No. 6, e0177628, 06.06.2017.

Research output: Contribution to journalArticle

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T1 - 3D bioprinting of methacrylated hyaluronic acid (MeHA) hydrogel with intrinsic osteogenicity

AU - Poldervaart,Michelle T.

AU - Goversen,Birgit

AU - De Ruijter,Mylène

AU - Abbadessa,Anna

AU - Melchels,Ferry

AU - Öner,F. Cumhur

AU - Dhert,Wouter J. A.

AU - Vermonden,Tina

AU - Alblas,Jacqueline

PY - 2017/6/6

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N2 - In bone regenerative medicine there is a need for suitable bone substitutes. Hydrogels have excellent biocompatible and biodegradable characteristics, but their visco-elastic properties limit their applicability, especially with respect to 3D bioprinting. In this study, we modified the naturally occurring extracellular matrix glycosaminoglycan hyaluronic acid (HA), in order to yield photo-crosslinkable hydrogels with increased mechanical stiffness and long-term stability, and with minimal decrease in cytocompatibility. Application of these tailor-made methacrylated hyaluronic acid (MeHA) gels for bone tissue engineering and 3D bioprinting was the subject of investigation. Visco-elastic properties of MeHA gels, measured by rheology and dynamic mechanical analysis, showed that irradiation of the hydrogels with UV light led to increased storage moduli and elastic moduli, indicating increasing gel rigidity. Subsequently, human bone marrow derived mesenchymal stromal cells (MSCs) were incorporated into MeHA hydrogels, and cell viability remained 64.4% after 21 days of culture. Osteogenic differentiation of MSCs occurred spontaneously in hydrogels with high concentrations of MeHA polymer, in absence of additional osteogenic stimuli. Addition of bone morphogenetic protein-2 (BMP-2) to the culture medium further increased osteogenic differentiation, as evidenced by increased matrix mineralisation. MeHA hydrogels demonstrated to be suitable for 3D bioprinting, and were printed into porous and anatomically shaped scaffolds. Taken together, photosensitive MeHA-based hydrogels fulfilled our criteria for cellular bioprinted bone constructs within a narrow window of concentration.

AB - In bone regenerative medicine there is a need for suitable bone substitutes. Hydrogels have excellent biocompatible and biodegradable characteristics, but their visco-elastic properties limit their applicability, especially with respect to 3D bioprinting. In this study, we modified the naturally occurring extracellular matrix glycosaminoglycan hyaluronic acid (HA), in order to yield photo-crosslinkable hydrogels with increased mechanical stiffness and long-term stability, and with minimal decrease in cytocompatibility. Application of these tailor-made methacrylated hyaluronic acid (MeHA) gels for bone tissue engineering and 3D bioprinting was the subject of investigation. Visco-elastic properties of MeHA gels, measured by rheology and dynamic mechanical analysis, showed that irradiation of the hydrogels with UV light led to increased storage moduli and elastic moduli, indicating increasing gel rigidity. Subsequently, human bone marrow derived mesenchymal stromal cells (MSCs) were incorporated into MeHA hydrogels, and cell viability remained 64.4% after 21 days of culture. Osteogenic differentiation of MSCs occurred spontaneously in hydrogels with high concentrations of MeHA polymer, in absence of additional osteogenic stimuli. Addition of bone morphogenetic protein-2 (BMP-2) to the culture medium further increased osteogenic differentiation, as evidenced by increased matrix mineralisation. MeHA hydrogels demonstrated to be suitable for 3D bioprinting, and were printed into porous and anatomically shaped scaffolds. Taken together, photosensitive MeHA-based hydrogels fulfilled our criteria for cellular bioprinted bone constructs within a narrow window of concentration.

U2 - 10.1371/journal.pone.0177628

DO - 10.1371/journal.pone.0177628

M3 - Article

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JF - PLOS ONE

SN - 1932-6203

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ER -

Poldervaart MT, Goversen B, De Ruijter M, Abbadessa A, Melchels F, Öner FC et al. 3D bioprinting of methacrylated hyaluronic acid (MeHA) hydrogel with intrinsic osteogenicity. PLOS ONE. 2017 Jun 6;12(6). e0177628. Available from, DOI: 10.1371/journal.pone.0177628