New materials for freeform (FRESH) Bioprinting

By ML -

FRESH bioprinting 

The beginning

Bioprinting of soft materials such as hydrogels have long been impaired by their inability to hold its own form, rendering them "unprintable". Thankfully, in 2015, TJ Hinton and Adam Feinberg published a Science paper introducing the idea of FRESH bioprinting. The term "FRESH" stands for freeform reversible embedding of suspended hydrogels and herein they introduced the idea of using a thermo-reversible support bath to enable in situ bioprinting of complex 3D biological structures. The beauty of this technique lies in the freedom to print complex structures including overhangs while being supported by the temporary gel bath. This breakthrough innovation has truly enable researchers around the world to bioprint complex and intricate structures out of soft biological materials such as collagen, thus pulling off additive manufacturing of realistic tissue models like never before.

This video demonstration shows the FRESH printing technique with collagen bioink


Empowered by this novel printing approach, it should come as no surprise to anyone that multiple research groups around the world have started innovating in new combinations of materials to enable bioprinting of a variety of soft biomaterials and hydrogels.

New materials for freeform bioprinting

Last month, Turkish researchers from the Sabanci Nanotechnology Research and Application Center  reported a novel nanoclay-hydrogel support bath that enables bioprinting of alginate-based hydrogels in Scientific Reports. The proposed new composite support hydrogel, made of Pluronic and Laponite nanoclay, provides a unique combination of Pluronic's thermo-reversibility and time-dependent shear thinning behavior of Laponite. Different formulations with varying concentrations of Pluronic-Laponite and calcium chloride were extensively studied to determine the optimal rheological properties for bioprinting. Check out this open access paper to read the details of this investigation.

Carbohydrazide is an oxygen scavenger commonly used in water treatments but here, researchers at Penn State University led by Ibraham Ozbolat are exploring its use to create a novel hydrogel support bath consisting of carbohydrazide-modified gelatin combined with oxidized alginate solution. The proposed support hydrogel bath enabled bioprinting of cells in physiologically-relevant cell densities, demonstrated with human mesenchymal stromal cells (hMSCs) and human umbilical vein endothelial cells (HUVECs). This recently published work can be found in ACS Applied Materials & Interfaces.

A long-standing challenge faced in the tissue engineering field has been diffusion limitations resulting in inefficient nutrient delivery within large constructs. The current approach that many groups are looking into to solve this problem is to build a vascularized network. However, researchers at Zhejiang University led by Yong He have decided to take a slightly different approach, and figured out how they could create a mesoscale pore network that would provide enhanced nutrient delivery and cell growth.

By utilizing the freeform bioprinting technique, this group has developed a novel sacrificial hydrogel support bath that enables bioprinting of structures with the proposed mesoscale pore networks. The sacrificial bath consists of cell/gelatin-methacrylate (GelMA) and gelled gelatin microgel. By utilizing a combination of thermo-crosslinking and photo-crosslinking, the mesoscale pore network is formed within printed constructs after the gelatin microgel is dissolved. A proof-of-concept application was demonstrated using osteoblasts and HUVECs. To learn more, read this Bio-design and Manufacturing publication.

Bioelastomers are a unique class of biomaterials providing high flexibility and elastic properties that can serve as a mechanical stimuli for tissue engineering applications. Researchers in the University of Toronto led by Milica Radisic recently reported FRESH bioprinting of bioelastomers and introduced a novel class of photocrosslinkable bioelastomer prepolymers made of dimethyl itaconate, 1,8-octanediol, and triethyl citrate. These materials supported the culture of cells, promoting adhesion and proliferation of HUVECs and was explored in this paper for the printing of vascular tubes. Dig into the details of this ACS Biomaterials Science & Engineering paper.

All of the work mentioned above have only been reported in the last 4 months, we should expect to see more ideas and innovation arising in this area of bioprinting. Stay tuned for more...

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