Thermo-sensitive polysaccharide based-hydrogels with tunable rheological properties: a novel class of bioinks for cartilage 3D-bioprinting
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1
Utrecht University, Department of Pharmaceutics, Netherlands
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2
University Medical Centre Utrecht, Department of Orthopaedics, Netherlands
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3
University Medical Centre Utrecht, Department of Oral and Maxillofacial Surgery & Special Dental Care, Netherlands
Introduction: 3D-bioprinting is an emerging technique for the generation of customized, implantable 3D cell-containing constructs. Specifically, robotic dispensing of hydrogel-based bioinks allows for the development of hydrogel scaffolds that, at least to a certain extent, recapitulate the complexity of human tissues such as multi-layered cartilage. Nevertheless, the use of precise dispensing requires specific rheological properties of the hydrogel materials. In this study, a novel class of candidate bioinks, composed of a thermo-sensitive triblock copolymer and polysaccharides were investigated for their rheological properties and translation to cartilage 3D-bioprinting.
Materials and Methods: A copolymer composed of a polyethylene glycol (PEG) mid-block, flanked by two partially methacrylated poly(N-(2-hydroxypropyl)methacrylamide-mono-di-lactate outer blocks (pMHPMAlac-PEG-pMHPMAlac), as well as methacrylated hyaluronic acid (MeHA) and chondroitin sulfate (MeCS) were synthesized, as previously described[1]-[3]. Rheological properties of polymer solutions based on pMHPMAlac-PEG-pMHPMAlac (22-30% wt) and MeHA (0.5-2% wt) were investigated under strain, temperature, shear rate and stress ramps using a rheometer. 3D-printing of (chondrocyte-laden) hydrogels composed of pMHPMAlac-PEG-pMHPMAlac and MeHA or MeCS was implemented using a 3D-bioprinter equipped with a UV lamp. Cell viability was evaluated after days 1 and 7. 3D-printed constructs with cartilage inspired zonal organization were also generated by sequential printing of two hydrogel compositions, loaded with dye-labeled cells or fluorescent microspheres (MS).
Results and Discussion: Polymer solutions of pMHPMAlac-PEG-pMHPMAlac and MeHA showed strain-softening, thermo-responsive, shear thinning and yield stress behavior. These interesting properties for 3D-printing applications were highly dependent on the content of the two polymers. An increase of pMHPMAlac-PEG-pMHPMAlac resulted in increasingly stiff material and high yield stress. On the contrary, an increase in MeHA resulted in hydrogels with lower moduli and yield stress, despite an increased total polymer concentration. Based on rheological properties, the optimal concentrations were chosen for 3D-printing of polymer solutions, which led to the generation of porous constructs with high shape fidelity and tunable porosity. Chondrocyte-laden hydrogels were 3D-printed and more than 80% of the cells remained viable. In addition, zonally organized printed constructs were generated. A double-layered architecture with distinct cell populations was achieved (Fig. 1).
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Conclusions: Hydrogels composed of pMHPMAlac-PEG-pMHPMAlac/MeHA or MeCS display rheological properties interesting for 3D-printing. Using a cell-friendly procedure, these hydrogels were successfully 3D-shaped in tissue-engineered constructs with a tunable degree of complexity. These aspects highlight the potential of the described bioinks for cartilage biofabrication.
FP7/2007-2013 (grant agreement n 309962-HydroZONES)
References:
[1] Vermonden, T.; Fedorovich, N. E.; van Geemen, D.; Alblas, J.; van Nostrum, C. F.; Dhert, W. J. A.; Hennink, W. E. Biomacromolecules 2008, 9 (3), 919–926.
[2] Hachet, E.; Van Den Berghe, H.; Bayma, E.; Block, M. R.; Auzély-Velty, R. Biomacromolecules 2012, 13 (6), 1818–1827.
[3] Oudshoorn, M. H. M.; Rissmann, R.; Bouwstra, J. A.; Hennink, W. E. Polymer 2007, 48 (7), 1915–1920.
Keywords:
biomaterial,
Bioprinting,
3D scaffold,
Polymeric material
Conference:
10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016.
Presentation Type:
Poster
Topic:
Biomaterials in printing
Citation:
Abbadessa
A,
Mouser
VH,
Blokzijl
MM,
Gawlitta
D,
Malda
J,
Hennink
WE and
Vermonden
T
(2016). Thermo-sensitive polysaccharide based-hydrogels with tunable rheological properties: a novel class of bioinks for cartilage 3D-bioprinting.
Front. Bioeng. Biotechnol.
Conference Abstract:
10th World Biomaterials Congress.
doi: 10.3389/conf.FBIOE.2016.01.02138
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Received:
27 Mar 2016;
Published Online:
30 Mar 2016.