A team of researchers from Rice University (TX, USA) has used powdered sugar to 3D print templates for blood vessel production, keeping densely packed living cells in large constructs alive for 2 weeks.
One of the biggest hurdles to engineering clinically relevant tissues is packing a large tissue structure with hundreds of millions of living cells. Delivering enough oxygen and nutrients to all the cells across that large volume of tissue becomes a monumental challenge,” explained the study’s lead author Ian Kinstlinger, a bioengineering graduate student in Rice's Brown School of Engineering.
Described in Nature Biomedical Engineering, the technique is based on blood vessel patterns observed in nature, as complex networks ensure the provision of oxygen and nutrients across larger tissue structures.
By developing new technologies and materials to mimic naturally occurring vascular networks, we're getting closer to the point that we can provide oxygen and nutrients to a sufficient number of cells to get meaningful long-term therapeutic function," Kinstlinger continued.
We're using algorithms inspired by nature to create functional networks for tissues. Because our approach is algorithmic, it's possible to create customized networks for different uses." Jessica Rosenkrantz, Co-Founder and Creative Director of Nervous System (NY, USA) and a study co-author commented further.
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The team utilized a selective laser sintering methodology to 3D print the sugar templates for the intricate and complex vascular networks.
The 3D-printing process we developed here is like making a very precise creme brulee. There are certain architectures - such as overhanging structures, branched networks and multivascular networks - which you really can't do well with extrusion printing. Selective laser sintering gives us far more control in all three dimensions, allowing us to easily access complex topologies while still preserving the utility of the sugar material," explained Jordan Miller, Assistant Professor of Bioengineering at Rice University.
The team used a combination of different sugars to print the template, allowing the template to quickly dissolve when water was applied without the risk of damaging any living cells. A gel containing a mixture of living cells was then applied to the sugar template, becoming semi-solid within just a few minutes. The final step involved the application of water to dissolve the structure, leaving a hollow network for nutrients and oxygen.
A major benefit of this approach is the speed at which we can generate each tissue structure. We can create some of the largest tissue models yet demonstrated in under 5 minutes,” Kinstlinger added.
Once the vascular networks had been developed, the team then seeded the structures with rodent hepatocytes to test the survival and function of the surrounding tissues.
We showed that perfusion through 3D vascular networks allows us to sustain these large liver-like tissues. While there are still long-standing challenges associated with maintaining hepatocyte function, the ability to both generate large volumes of tissue and sustain the cells in those volumes for sufficient time to assess their function is an exciting step forward," Miller concluded.
Sources: Kinstlinger IS, Saxton SH, Calderon GA et al. Generation of model tissues with dendritic vascular networks via sacrificial laser-sintered carbohydrate templates. Nat Biomed Eng. doi: 10.1038/s41551-020-0566-1(2020); http://news.rice.edu/2020/06/29/laser-welded-sugar-sweet-way-to-3d-print-blood-vessels/
Lead image: A sample of blood vessel templates that Rice University bioengineers 3D-printed using a special blend of powdered sugars. Credit: Brandon Martin/Rice University.