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International
Journal of Bioprinting
RESEARCH ARTICLE
Mimicking human skin constructs using
norbornene-pullulan-based hydrogels
Angela Cirulli 1 id , Livia Neves Borgheti-Cardoso 1 id , Núria Torras * ,
1 id
and Elena Martínez 1,2,3 id
*
1 Biomimetic Systems for Cell Engineering Laboratory, Institute for Bioengineering of Catalonia,
The Barcelona Institute of Science and Technology, Barcelona, Spain
2 Centro de Investigación Biomédica en Red, Madrid, Spain
3 Department of Electronics and Biomedical Engineering, University of Barcelona, Barcelona, Spain
Abstract
There has been a huge demand for engineered skin tissues in the realms of both
in vitro and in vivo applications. Selecting the right material scaffold is a critical
consideration in making engineered skin tissues, since it should possess a good
balance between elasticity and mechanical stability while promoting an adequate
cell microenvironment to support both the dermal and the epidermal compartments
of skin tissue. In this study, 3D-bioprinted norbornene-pullulan photocrosslinkable
hydrogels were utilized as alternative scaffolds to produce epithelized dermal skin
models. By employing visible light, 2.5 mm cell-laden hydrogels could be printed
3
in 10 s. The thiol-ene photocrosslinking chemistry employed in this work enabled
*Corresponding authors: the formation of a well-defined extracellular matrix with orthogonal crosslinks,
Núria Torras
(ntorras@ibecbarcelona.eu) where encapsulated fibroblasts maintained high cellular viability rates. Through
Elena Martínez this method, an epidermal layer could be grown on top of the fibroblasts. The
(emartinez@ibecbarcelona.eu) coexistence and interaction of human fibroblasts and keratinocytes were visualized
by determining the expression of specific markers. This approach represents a
Citation: Cirulli A,
Borgheti-Cardoso LN, Torras N, promising starting point for the development of photocrosslinkable hydrogel-based
Martínez E. Mimicking human human skin constructs by using thiol-ene norbornene chemistry, paving the way
skin constructs using norbornene- toward manufacture of complex in vitro models of human tissues.
pullulan-based hydrogels.
Int J Bioprint. 2024;10(4):3395.
doi: 10.36922/ijb.3395
Keywords: Skin models; Photocrosslinkable hydrogels; Pullulan;
Received: April 9, 2024 Light-based 3D bioprinting
Accepted: May 24, 2024
Published Online: July 3, 2024
Copyright: © 2024 Author(s).
This is an Open Access article
distributed under the terms of the 1. Introduction
Creative Commons Attribution
License, permitting distribution, The skin structure can be organized into three major layers, namely hypodermis,
and reproduction in any medium, dermis, and epidermis, with each of the layers providing different mechanical properties
provided the original work is depending on its cellular composition and type of structure. Engineered skin tissues
1
properly cited.
can be employed in clinical applications, including skin substitution and advanced
Publisher’s Note: AccScience wound dressing, as well as in the pre-clinical scenarios to facilitate drug absorption,
Publishing remains neutral with disease modeling, and cosmetic studies. An ideal engineered skin tissue should be easy
regard to jurisdictional claims in
published maps and institutional to prepare, resistant mechanical shear forces, and suitable for cells to adhere, grow, and
affiliations. vascularize, in both epidermal and dermal compartments. 2,3
Volume 10 Issue 4 (2024) 222 doi: 10.36922/ijb.3395

