Cryogenic 3D Printing of Super Soft Hydrogels

Zhengchu Tan,Cristian Parisi,Lucy Di Silvio,Daniele Dini,Antonio Elia Forte

doi:10.1038/s41598-017-16668-9

Zhengchu Tan, Cristian Parisi + Show 3 more

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https://doi.org/10.1038/s41598-017-16668-9

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Abstract

Conventional 3D bioprinting allows fabrication of 3D scaffolds for biomedical applications. In this contribution we present a cryogenic 3D printing method able to produce stable 3D structures by utilising the liquid to solid phase change of a composite hydrogel (CH) ink. This is achieved by rapidly cooling the ink solution below its freezing point using solid carbon dioxide (CO2) in an isopropanol bath. The setup was able to successfully create 3D complex geometrical structures, with an average compressive stiffness of O(1) kPa (0.49 ± 0.04 kPa stress at 30% compressive strain) and therefore mimics the mechanical properties of the softest tissues found in the human body (e.g. brain and lung). The method was further validated by showing that the 3D printed material was well matched to the cast-moulded equivalent in terms of mechanical properties and microstructure. A preliminary biological evaluation on the 3D printed material, coated with collagen type I, poly-L-lysine and gelatine, was performed by seeding human dermal fibroblasts. Cells showed good attachment and viability on the collagen-coated 3D printed CH. This greatly widens the range of applications for the cryogenically 3D printed CH structures, from soft tissue phantoms for surgical training and simulations to mechanobiology and tissue engineering.

Highlights

In the past three decades, 3D bioprinting has become one of the leading techniques for the replication of real tissue geometries, with the potential to mimic the soft tissue microstructure
This article demonstrates the fabrication of mechanically accurate 3D printed composite hydrogels that mimic the stiffness of super soft tissues through the use of a novel printing setup based on cryogenic theory
The ink used in this work is a composite hydrogel of poly(vinyl) alcohol (PVA) and Phytagel, which has been pioneered by Leibinger et al.[22] and Forte et al.[23,24,25] to mimic soft tissues, such as brain, with stiffness of O(1) kPa

Summary

Introduction

In the past three decades, 3D bioprinting has become one of the leading techniques for the replication of real tissue geometries, with the potential to mimic the soft tissue microstructure. A 3D printing technique that is able to produce geometrically and mechanically accurate scaffolds could hold enormous potential in regenerative medicine and biomimetics[14]. This reinforces the importance of soft 3D printing. The stiffness of the alginate ink was reported to be O(10) kPa, and not comparable with that of super soft tissues, such as human brain or lung (O(1) kPa15–18). This article demonstrates the fabrication of mechanically accurate 3D printed composite hydrogels that mimic the stiffness of super soft tissues through the use of a novel printing setup based on cryogenic theory. The ink used in this work is a composite hydrogel of poly(vinyl) alcohol (PVA) and Phytagel, which has been pioneered by Leibinger et al.[22] and Forte et al.[23,24,25] to mimic soft tissues, such as brain, with stiffness of O(1) kPa

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