A novel support material for 3D bioprinting and post-printing tissue growth: Print and Grow

Project Information

Print and Grow

Grant agreement ID: 101069174

DOI

10.3030/101069174

Project closed

EC signature date 30 May 2022

Start date 1 June 2022

End date 30 November 2023

Funded under

• European Research Council (ERC)

Total cost

No data

EU contribution

€ 150 000,00

Coordinated by

TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
Israel

Periodic Reporting for period 1 - Print and Grow (A novel support material for 3D bioprinting and post-printing tissue growth: Print and Grow)

Reporting period: 2022-06-01 to 2023-11-30

Summary of the context and overall objectives of the project

In the rapidly evolving field of tissue engineering, a major challenge is the creation of 3D constructs that replicate the structural and functional attributes of living tissue, leading to a gap in applications such as regenerative medicine and drug testing. The advent of 3D bioprinting, particularly extrusion-based techniques, has opened new avenues in fabricating cell-containing 3D structures. However, the reliability of the bioprinted structures over time is compromised by their tendency to shrink and deform, undermining their practical utility.
Here we aim to stabilize bioprinted tissues and substantially improve the reliability and applicability of the 3D bioprinting technique through a novel "Print and Grow" method. This approach involves printing directly into a specially designed granular support material (CarGrow) which assists in maintaining the shape and size of the bioprinted constructs during the critical maturation period. Unlike current methods, which necessitate the removal of constructs from support materials post-printing, this new technique enables the constructs to remain within the support material. This significantly reduces post-printing contraction and deformation, ensuring the preservation of the printed pattern and structure. The use of CarGrow as the support material is a breakthrough, offering compatibility with both the printing process and tissue culture requirements.
This project stands to make a substantial contribution to the field of tissue engineering. By enhancing the structural stability of bioprinted constructs, it promises to bridge the gap between the potential and actual applicability of 3D bioprinting in critical areas like regenerative medicine and drug discovery. The "Print and Grow" method aims to enable the fabrication of complex structures that are not only reliable and reproducible but also tailored to specific applications and patient needs. The successful implementation of this technique will significantly advance the field of bioprinting offering a universal and user-friendly tool. The project's outcome will potentially contribute to personalized medicine, offering new solutions for tissue transplantation and the testing of pharmaceuticals.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

We developed the "Print and Grow" technology, which entailed embedding living cells within bioinks, extruding them layer by layer into a granular support material, and leaving them in the support material for cultivation to aid post-printing maturation of the tissue. This approach ensured high fidelity and precise fabrication of complex structures, closely mimicking living tissue properties.
A significant part of our work involved the development and optimization of κ-Carrageenan-based microgels (CarGrow). These microgels were engineered to provide mechanical support to the bioprinted constructs, thus enhancing their long-term structural stability. We conducted comprehensive rheological studies on granular hydrogels. By examining different microgel stiffness levels and packing densities, we gained insights into the viscoelastic properties of these materials, critical for their application in bioprinting and tissue cultivation. Upon defining the optimal CarGrow properties we demonstrated its applicability for a broad range of living tissues.
Main Achievements:
1. Overcoming Post-Printing Challenges:
The "Print and Grow" method effectively addressed the nonuniform shrinkage and deformation issues encountered during the post-printing tissue maturation period. This resulted in engineered constructs with predictable size and shape, significantly improving the reliability of 3D bioprinted tissues.
2. Enhanced Cell Viability and Functionality:
Our approach markedly improved cell viability within bioprinted tissues. The CarGrow environment proved conducive to cell growth and differentiation, leading to the development of tissues that were functionally closer to their natural counterparts.
3. Universal Support Material:
We identified CarGrow as a universal support material. This was a crucial finding as it demonstrated CarGrow's compatibility with a wide range of tissues, including adipose, pancreatic, skeletal muscle, and bone tissues, thereby broadening the scope of its application.
4. Live Imaging Capability:
The project also pioneered methods for live imaging within the CarGrow environment. This innovation is significant for real-time monitoring of tissue development and integrity, a critical aspect in the field of tissue engineering.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The project’s outcome presents a significant breakthrough in extrusion 3D bioprinting by successfully bridging the gap between the potential and actual applicability of the technique in tissue engineering. The developed here Print and Grow technology is a reliable, user-friendly, and cost-efficient approach for preserving the structural stability and viability of bioprinted constructs. It universal applicability for various tissue types paves the way for customizable and reproducible fabrication of complex tissue structures, tailored to specific applications in regenerative medicine and drug testing. To ensure the technology’s entrance to the market, we initiated collaborations with retailers in the 3D bioprinting field.