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Additive manufacturing of photo-crosslinked gelatin scaffolds for adipose tissue engineering

Liesbeth Tytgat (UGent) , Lana Van Damme (UGent) , Jasper Van Hoorick (UGent) , Heidi Declercq (UGent) , Hugo Thienpont (UGent) , Heidi Ottevaere (UGent) , Phillip Blondeel (UGent) , Peter Dubruel (UGent) and Sandra Van Vlierberghe (UGent)
(2019) ACTA BIOMATERIALIA. 94. p.340-350
Author
Abstract
There exists a clear clinical need for adipose tissue reconstruction strategies to repair soft tissue defects which outperform the currently available approaches. In this respect, additive manufacturing has shown to be a promising alternative for the development of larger constructs able to support adipose tissue engineering. In the present work, a thiol-ene photo-click crosslinkable gelatin hydrogel was developed which allowed extrusion-based additive manufacturing into porous scaffolds. To this end, norbornenefunctionalized gelatin (Gel-NB) was combined with thiolated gelatin (Gel-SH). The application of a macromolecular gelatin-based thiolated crosslinker holds several advantages over conventional crosslinkers including cell-interactivity, less chance at phase separation between scaffold material and crosslinker and the formation of a more homogeneous network. Throughout the paper, these photo click scaffolds were benchmarked to the conventional methacrylamide-modified gelatin (Gel-MA). The results indicated that stable scaffolds could be realized which were further characterized physicochemically by performing swelling, mechanical and in vitro biodegradability assays. Furthermore, the seeded adipose tissue-derived stem cells (ASCs) remained viable (>90%) up to 14 days and were able to proliferate. In addition, the cells could be differentiated into the adipogenic lineage on the photo click crosslinked scaffolds, thereby performing better than the cells supported by the frequently reported Gel-MA scaffolds. As a result, the developed photo-click crosslinked scaffolds can be considered a promising candidate towards adipose tissue engineering and a valuable alternative for the omnipresent Gel-MA. Statement of Significance The field of adipose tissue engineering has emerged as a promising strategy to repair soft tissue defects. Herein, Gel-NB/Gel-SH gelatin-based hydrogel scaffolds were produced using extrusion-based additive manufacturing. Using a cell-interactive, thiolated gelatin crosslinker, a homogeneous network was formed and the risk of phase separation between norbornene-modified gelatin and macromolecular crosslinkers was reduced. UV-induced crosslinking of these materials is based on step growth polymerization which requires less free radicals to enable polymerization. Our results demonstrated the potential of the developed scaffolds, due to their favourable physico-chemical characteristics as well as their adipogenic differentiation potential when benchmarked to Gel-MA scaffolds. Hence, the hydrogels could be of great interest towards future development of adipose tissue constructs and tissue engineering in general.
Keywords
Hydrogels, Thiol-ene photo-click chemistry, Extrusion-based 3D printing, Adipose tissue engineering, Additive manufacturing, MECHANICAL-PROPERTIES, HYDROGEL DEVELOPMENT, DIFFERENTIATION, FABRICATION, ELASTICITY, LINKING, DESIGN, MUSCLE, CELLS, PART

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Citation

Please use this url to cite or link to this publication:

MLA
Tytgat, Liesbeth et al. “Additive Manufacturing of Photo-crosslinked Gelatin Scaffolds for Adipose Tissue Engineering.” ACTA BIOMATERIALIA 94 (2019): 340–350. Print.
APA
Tytgat, Liesbeth, Van Damme, L., Van Hoorick, J., Declercq, H., Thienpont, H., Ottevaere, H., Blondeel, P., et al. (2019). Additive manufacturing of photo-crosslinked gelatin scaffolds for adipose tissue engineering. ACTA BIOMATERIALIA, 94, 340–350.
Chicago author-date
Tytgat, Liesbeth, Lana Van Damme, Jasper Van Hoorick, Heidi Declercq, Hugo Thienpont, Heidi Ottevaere, Phillip Blondeel, Peter Dubruel, and Sandra Van Vlierberghe. 2019. “Additive Manufacturing of Photo-crosslinked Gelatin Scaffolds for Adipose Tissue Engineering.” Acta Biomaterialia 94: 340–350.
Chicago author-date (all authors)
Tytgat, Liesbeth, Lana Van Damme, Jasper Van Hoorick, Heidi Declercq, Hugo Thienpont, Heidi Ottevaere, Phillip Blondeel, Peter Dubruel, and Sandra Van Vlierberghe. 2019. “Additive Manufacturing of Photo-crosslinked Gelatin Scaffolds for Adipose Tissue Engineering.” Acta Biomaterialia 94: 340–350.
Vancouver
1.
Tytgat L, Van Damme L, Van Hoorick J, Declercq H, Thienpont H, Ottevaere H, et al. Additive manufacturing of photo-crosslinked gelatin scaffolds for adipose tissue engineering. ACTA BIOMATERIALIA. OXON, ENGLAND: ELSEVIER SCI LTD; 2019;94:340–50.
IEEE
[1]
L. Tytgat et al., “Additive manufacturing of photo-crosslinked gelatin scaffolds for adipose tissue engineering,” ACTA BIOMATERIALIA, vol. 94, pp. 340–350, 2019.
@article{8627240,
  abstract     = {There exists a clear clinical need for adipose tissue reconstruction strategies to repair soft tissue defects which outperform the currently available approaches. In this respect, additive manufacturing has shown to be a promising alternative for the development of larger constructs able to support adipose tissue engineering. In the present work, a thiol-ene photo-click crosslinkable gelatin hydrogel was developed which allowed extrusion-based additive manufacturing into porous scaffolds. To this end, norbornenefunctionalized gelatin (Gel-NB) was combined with thiolated gelatin (Gel-SH). The application of a macromolecular gelatin-based thiolated crosslinker holds several advantages over conventional crosslinkers including cell-interactivity, less chance at phase separation between scaffold material and crosslinker and the formation of a more homogeneous network. Throughout the paper, these photo click scaffolds were benchmarked to the conventional methacrylamide-modified gelatin (Gel-MA). The results indicated that stable scaffolds could be realized which were further characterized physicochemically by performing swelling, mechanical and in vitro biodegradability assays. Furthermore, the seeded adipose tissue-derived stem cells (ASCs) remained viable (>90%) up to 14 days and were able to proliferate. In addition, the cells could be differentiated into the adipogenic lineage on the photo click crosslinked scaffolds, thereby performing better than the cells supported by the frequently reported Gel-MA scaffolds. As a result, the developed photo-click crosslinked scaffolds can be considered a promising candidate towards adipose tissue engineering and a valuable alternative for the omnipresent Gel-MA. 

Statement of Significance 

The field of adipose tissue engineering has emerged as a promising strategy to repair soft tissue defects. Herein, Gel-NB/Gel-SH gelatin-based hydrogel scaffolds were produced using extrusion-based additive manufacturing. Using a cell-interactive, thiolated gelatin crosslinker, a homogeneous network was formed and the risk of phase separation between norbornene-modified gelatin and macromolecular crosslinkers was reduced. UV-induced crosslinking of these materials is based on step growth polymerization which requires less free radicals to enable polymerization. Our results demonstrated the potential of the developed scaffolds, due to their favourable physico-chemical characteristics as well as their adipogenic differentiation potential when benchmarked to Gel-MA scaffolds. Hence, the hydrogels could be of great interest towards future development of adipose tissue constructs and tissue engineering in general. },
  author       = {Tytgat, Liesbeth and Van Damme, Lana and Van Hoorick, Jasper and Declercq, Heidi and Thienpont, Hugo and Ottevaere, Heidi and Blondeel, Phillip and Dubruel, Peter and Van Vlierberghe, Sandra},
  journal      = {ACTA BIOMATERIALIA},
  keywords     = {Hydrogels,Thiol-ene photo-click chemistry,Extrusion-based 3D printing,Adipose tissue engineering,Additive manufacturing,MECHANICAL-PROPERTIES,HYDROGEL DEVELOPMENT,DIFFERENTIATION,FABRICATION,ELASTICITY,LINKING,DESIGN,MUSCLE,CELLS,PART},
  pages        = {340--350},
  publisher    = {ELSEVIER SCI LTD},
  title        = {Additive manufacturing of photo-crosslinked gelatin scaffolds for adipose tissue engineering},
  url          = {http://dx.doi.org/10.1016/j.actbio.2019.05.062},
  volume       = {94},
  year         = {2019},
}

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