Bio-resin for high resolution lithography-based biofabrication of complex cell-laden constructs

Khoon S. Lim, Riccardo Levato, Pedro F. Costa, Miguel D. Castilho, Cesar Alcala-Orozco, Kim M. A. van Dorenmalen, Ferry Melchels, Debby Gawlitta, Gary J. Hooper, Jos Malda, Tim B. F. Woodfield

Research output: Contribution to journalArticle

Abstract

Lithography-based three-dimensional (3D) printing technologies allow high spatial resolution that exceeds that of typical extrusion-based bioprinting approaches, allowing to better mimic the complex architecture of biological tissues. Additionally, lithographic printing via digital light processing (DLP) enables fabrication of free-form lattice and patterned structures which cannot be easily produced with other 3D printing approaches. While significant progress has been dedicated to the development of cell-laden bioinks for extrusion-based bioprinting, less attention has been directed towards the development of cyto-compatible bio-resins and their application in lithography-based biofabrication, limiting the advancement of this promising technology. In this study, we developed a new bio-resin based on methacrylated poly(vinyl alcohol) (PVA-MA), gelatin-methacryloyl (Gel-MA) and a transition metal-based visible light photoinitiator. The utilization of a visible light photo-initiating system displaying high molar absorptivity allowed the bioprinting of constructs with high resolution features, in the range of 25–50 μm. Biofunctionalization of the resin with 1 wt% Gel-MA allowed long term survival (>90%) of encapsulated cells up to 21 d, and enabled attachment and spreading of endothelial cells seeded on the printed hydrogels. Cell-laden hydrogel constructs of high resolution with complex and ordered architecture were successfully bioprinted, where the encapsulated cells remained viable, homogenously distributed and functional. Bone and cartilage tissue synthesis was confirmed by encapsulated stem cells, underlining the potential of these DLP-bioprinted hydrogels for tissue engineering and biofabrication. Overall, the PVA-MA/Gel-MA bio-resin is a promising material for biofabrication and provides important cues for the further development of lithography-based bioprinting of complex, free-form living tissue analogues.
LanguageEnglish
Article number034101
JournalBiofabrication
Volume10
Issue number3
DOIs
Publication statusPublished - 11 May 2018

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Lithography
Gelatin
Resins
Printing
Hydrogels
Tissue
Extrusion
Hydrogel
Bioelectric potentials
Endothelial cells
Cartilage
Processing
Stem cells
Tissue engineering
Transition metals
Bone
Alcohols
Fabrication

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Lim, K. S., Levato, R., Costa, P. F., Castilho, M. D., Alcala-Orozco, C., van Dorenmalen, K. M. A., ... Woodfield, T. B. F. (2018). Bio-resin for high resolution lithography-based biofabrication of complex cell-laden constructs. Biofabrication, 10(3), [034101]. https://doi.org/10.1088/1758-5090/aac00c
Lim, Khoon S. ; Levato, Riccardo ; Costa, Pedro F. ; Castilho, Miguel D. ; Alcala-Orozco, Cesar ; van Dorenmalen, Kim M. A. ; Melchels, Ferry ; Gawlitta, Debby ; Hooper, Gary J. ; Malda, Jos ; Woodfield, Tim B. F. / Bio-resin for high resolution lithography-based biofabrication of complex cell-laden constructs. In: Biofabrication. 2018 ; Vol. 10, No. 3.
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abstract = "Lithography-based three-dimensional (3D) printing technologies allow high spatial resolution that exceeds that of typical extrusion-based bioprinting approaches, allowing to better mimic the complex architecture of biological tissues. Additionally, lithographic printing via digital light processing (DLP) enables fabrication of free-form lattice and patterned structures which cannot be easily produced with other 3D printing approaches. While significant progress has been dedicated to the development of cell-laden bioinks for extrusion-based bioprinting, less attention has been directed towards the development of cyto-compatible bio-resins and their application in lithography-based biofabrication, limiting the advancement of this promising technology. In this study, we developed a new bio-resin based on methacrylated poly(vinyl alcohol) (PVA-MA), gelatin-methacryloyl (Gel-MA) and a transition metal-based visible light photoinitiator. The utilization of a visible light photo-initiating system displaying high molar absorptivity allowed the bioprinting of constructs with high resolution features, in the range of 25–50 μm. Biofunctionalization of the resin with 1 wt{\%} Gel-MA allowed long term survival (>90{\%}) of encapsulated cells up to 21 d, and enabled attachment and spreading of endothelial cells seeded on the printed hydrogels. Cell-laden hydrogel constructs of high resolution with complex and ordered architecture were successfully bioprinted, where the encapsulated cells remained viable, homogenously distributed and functional. Bone and cartilage tissue synthesis was confirmed by encapsulated stem cells, underlining the potential of these DLP-bioprinted hydrogels for tissue engineering and biofabrication. Overall, the PVA-MA/Gel-MA bio-resin is a promising material for biofabrication and provides important cues for the further development of lithography-based bioprinting of complex, free-form living tissue analogues.",
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Lim, KS, Levato, R, Costa, PF, Castilho, MD, Alcala-Orozco, C, van Dorenmalen, KMA, Melchels, F, Gawlitta, D, Hooper, GJ, Malda, J & Woodfield, TBF 2018, 'Bio-resin for high resolution lithography-based biofabrication of complex cell-laden constructs', Biofabrication, vol. 10, no. 3, 034101. https://doi.org/10.1088/1758-5090/aac00c

Bio-resin for high resolution lithography-based biofabrication of complex cell-laden constructs. / Lim, Khoon S.; Levato, Riccardo; Costa, Pedro F.; Castilho, Miguel D.; Alcala-Orozco, Cesar; van Dorenmalen, Kim M. A.; Melchels, Ferry; Gawlitta, Debby; Hooper, Gary J.; Malda, Jos; Woodfield, Tim B. F.

In: Biofabrication, Vol. 10, No. 3, 034101, 11.05.2018.

Research output: Contribution to journalArticle

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T1 - Bio-resin for high resolution lithography-based biofabrication of complex cell-laden constructs

AU - Lim, Khoon S.

AU - Levato, Riccardo

AU - Costa, Pedro F.

AU - Castilho, Miguel D.

AU - Alcala-Orozco, Cesar

AU - van Dorenmalen, Kim M. A.

AU - Melchels, Ferry

AU - Gawlitta, Debby

AU - Hooper, Gary J.

AU - Malda, Jos

AU - Woodfield, Tim B. F.

PY - 2018/5/11

Y1 - 2018/5/11

N2 - Lithography-based three-dimensional (3D) printing technologies allow high spatial resolution that exceeds that of typical extrusion-based bioprinting approaches, allowing to better mimic the complex architecture of biological tissues. Additionally, lithographic printing via digital light processing (DLP) enables fabrication of free-form lattice and patterned structures which cannot be easily produced with other 3D printing approaches. While significant progress has been dedicated to the development of cell-laden bioinks for extrusion-based bioprinting, less attention has been directed towards the development of cyto-compatible bio-resins and their application in lithography-based biofabrication, limiting the advancement of this promising technology. In this study, we developed a new bio-resin based on methacrylated poly(vinyl alcohol) (PVA-MA), gelatin-methacryloyl (Gel-MA) and a transition metal-based visible light photoinitiator. The utilization of a visible light photo-initiating system displaying high molar absorptivity allowed the bioprinting of constructs with high resolution features, in the range of 25–50 μm. Biofunctionalization of the resin with 1 wt% Gel-MA allowed long term survival (>90%) of encapsulated cells up to 21 d, and enabled attachment and spreading of endothelial cells seeded on the printed hydrogels. Cell-laden hydrogel constructs of high resolution with complex and ordered architecture were successfully bioprinted, where the encapsulated cells remained viable, homogenously distributed and functional. Bone and cartilage tissue synthesis was confirmed by encapsulated stem cells, underlining the potential of these DLP-bioprinted hydrogels for tissue engineering and biofabrication. Overall, the PVA-MA/Gel-MA bio-resin is a promising material for biofabrication and provides important cues for the further development of lithography-based bioprinting of complex, free-form living tissue analogues.

AB - Lithography-based three-dimensional (3D) printing technologies allow high spatial resolution that exceeds that of typical extrusion-based bioprinting approaches, allowing to better mimic the complex architecture of biological tissues. Additionally, lithographic printing via digital light processing (DLP) enables fabrication of free-form lattice and patterned structures which cannot be easily produced with other 3D printing approaches. While significant progress has been dedicated to the development of cell-laden bioinks for extrusion-based bioprinting, less attention has been directed towards the development of cyto-compatible bio-resins and their application in lithography-based biofabrication, limiting the advancement of this promising technology. In this study, we developed a new bio-resin based on methacrylated poly(vinyl alcohol) (PVA-MA), gelatin-methacryloyl (Gel-MA) and a transition metal-based visible light photoinitiator. The utilization of a visible light photo-initiating system displaying high molar absorptivity allowed the bioprinting of constructs with high resolution features, in the range of 25–50 μm. Biofunctionalization of the resin with 1 wt% Gel-MA allowed long term survival (>90%) of encapsulated cells up to 21 d, and enabled attachment and spreading of endothelial cells seeded on the printed hydrogels. Cell-laden hydrogel constructs of high resolution with complex and ordered architecture were successfully bioprinted, where the encapsulated cells remained viable, homogenously distributed and functional. Bone and cartilage tissue synthesis was confirmed by encapsulated stem cells, underlining the potential of these DLP-bioprinted hydrogels for tissue engineering and biofabrication. Overall, the PVA-MA/Gel-MA bio-resin is a promising material for biofabrication and provides important cues for the further development of lithography-based bioprinting of complex, free-form living tissue analogues.

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DO - 10.1088/1758-5090/aac00c

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JO - Biofabrication

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Lim KS, Levato R, Costa PF, Castilho MD, Alcala-Orozco C, van Dorenmalen KMA et al. Bio-resin for high resolution lithography-based biofabrication of complex cell-laden constructs. Biofabrication. 2018 May 11;10(3). 034101. https://doi.org/10.1088/1758-5090/aac00c