Dynamic peptide-folding mediated biofunctionalization and modulation of hydrogels for 4D bioprinting

Christopher Aronsson,Sajjad Naeimipour,Jonas Christoffersson,Daniel Aili,Robert Selegård,Philip Lifwergren,Carl-Fredrik Mandenius,Michael Jury,Fatemeh Rasti Boroojeni

doi:10.1088/1758-5090/ab9490

Christopher Aronsson, Sajjad Naeimipour + Show 7 more

Open Access

https://doi.org/10.1088/1758-5090/ab9490

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Journal: Biofabrication	Publication Date: Jun 29, 2020
Citations: 45	License type: cc-by

Affiliation: Linköping University, University of Skövde

Abstract

Hydrogels are used in a wide range of biomedical applications, including three-dimensional (3D) cell culture, cell therapy and bioprinting. To enable processing using advanced additive fabrication techniques and to mimic the dynamic nature of the extracellular matrix (ECM), the properties of the hydrogels must be possible to tailor and change over time with high precision. The design of hydrogels that are both structurally and functionally dynamic, while providing necessary mechanical support is challenging using conventional synthesis techniques. Here, we show a modular and 3D printable hydrogel system that combines a robust but tunable covalent bioorthogonal cross-linking strategy with specific peptide-folding mediated interactions for dynamic modulation of cross-linking and functionalization. The hyaluronan-based hydrogels were covalently cross-linked by strain-promoted alkyne-azide cycloaddition using multi-arm poly(ethylene glycol). In addition, a de novo designed helix-loop-helix peptide was conjugated to the hyaluronan backbone to enable specific peptide-folding modulation of cross-linking density and kinetics, and hydrogel functionality. An array of complementary peptides with different functionalities was developed and used as a toolbox for supramolecular tuning of cell-hydrogel interactions and for controlling enzyme-mediated biomineralization processes. The modular peptide system enabled dynamic modifications of the properties of 3D printed structures, demonstrating a novel route for design of more sophisticated bioinks for four-dimensional bioprinting.

Highlights

Hydrogels are water-swollen polymer networks that can mimic mechanical, structural and chemical properties of the extracellular matrix (ECM) [1]
We have developed a novel strategy for 4D bioink development based on a modular peptide-polymer hybrid hydrogel system that combines the structural and mechanical robustness of bioorthogonal covalent cross-linking with specific supramolecular interactions that enable dynamic tuning of both mechanical properties and the biochemical functionality of the hydrogel
Hydrogel fabrication To allow for bioorthogonal SPAAC reaction with azide-moieties, HA was first modified with BCN groups (HA-BCN) using carbodiimide chemistry as previously described by us [37, 43]

Summary

Introduction

Hydrogels are water-swollen polymer networks that can mimic mechanical, structural and chemical properties of the extracellular matrix (ECM) [1]. ECMmimicking hydrogels further facilitates the development of human ex vivo tissue and disease models [8], including organs-on-chips [9], for cancer research [10], drug screening [11], and toxicology [12]. This can reduce both the need for animal models as well as time and costs in drug development [13]. The improvements in 3D cell culture strategies and 3D bioprinting put new requirements on hydrogels, both with respect to ECM mimicking capabilities and processability [16, 17]

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