Laser-welded sugar: Sweet way to 3D-print blood vessels
Intricate sugar networks dissolve to create pathways for blood in lab-
grown tissues

Date:
June 29, 2020
Source:
Rice University
Summary:
Bioengineers have shown they can keep densely packed cells alive
in lab- grown tissues by creating complex networks of branching
blood vessels from templates of 3D-printed sugar.



FULL STORY ========================================================================== Powdered sugar is the special ingredient in a Rice University recipe
for mimicking the body's intricate, branching blood vessels in lab-grown tissues.


==========================================================================
In research published today in the journal Nature Biomedical Engineering,
Rice bioengineers showed they could keep densely packed cells alive for
two weeks in relatively large constructs by creating complex blood vessel networks from templates of 3D-printed sugar.

"One of the biggest hurdles to engineering clinically relevant tissues
is packing a large tissue structure with hundreds of millions of living
cells," said study lead author Ian Kinstlinger, a bioengineering graduate student in Rice's Brown School of Engineering. "Delivering enough oxygen
and nutrients to all the cells across that large volume of tissue becomes
a monumental challenge." Kinstlinger explains that nature solved this
problem through the evolution of complex vascular networks, which weave
through our tissues and organs in patterns reminiscent of tree limbs. The vessels simultaneously become smaller in thickness but greater in number
as they branch away from a central trunk, allowing oxygen and nutrients
to be efficiently delivered to cells throughout the body.

"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 said.

The sugar templates were 3D-printed with an open-source, modified laser
cutter in the lab of study co-author Jordan Miller, an assistant professor
of bioengineering at Rice.



==========================================================================
"The 3D-printing process we developed here is like making a very precise
creme brulee," said Miller, whose original inspiration for the project
was an intricate dessert.

Miller said the complex, detailed structures are made possible by
selective laser sintering, a 3D-printing process that fuses minute grains
of powder into solid 3D objects. In contrast to more common extrusion
3D printing, where melted strands of material are deposited through a
nozzle, laser sintering works by gently melting and fusing small regions
in a packed bed of dry powder.

Both extrusion and laser sintering build 3D shapes one 2D layer at a
time, but the laser method enables the generation of structures which
would otherwise be prone to collapse if extruded, he said.

"There are certain architectures -- such as overhanging structures,
branched networks and multivascular networks -- which you really can't do
well with extrusion printing," said Miller, who demonstrated the concept
of sugar templating with a 3D extrusion printer during his postdoctoral
studies at the University of Pennsylvania. Miller began work on the laser-sintering approach shortly after joining Rice in 2013.

"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," he said.

Sugar is especially useful in creating blood vessel templates because it's durable when dry, and it rapidly dissolves in water without damaging
nearby cells. To make tissues, Kinstlinger uses a special blend of
sugars to print templates and then fills the volume around the printed
sugar network with a mixture of cells in liquid gel. The gel becomes
semisolid within minutes, and the sugar is then dissolved and flushed
away to leave an open passageway for nutrients and oxygen.



==========================================================================
"A major benefit of this approach is the speed at which we can generate
each tissue structure," Kinstlinger said. "We can create some of the
largest tissue models yet demonstrated in under five minutes." Miller
said the new study answers two important questions: What sugars can be
sintered into coherent structures, and what computational algorithms
can derive complex, branching architectures that mimic those found in
nature? The computational algorithm that generated the treelike vascular architectures in the study was created in collaboration with Nervous
System, a design studio that uses computer simulation to make unique art, jewelry and housewares that are inspired by patterns found in nature.

"We're using algorithms inspired by nature to create functional networks
for tissues," said Jessica Rosenkrantz, co-founder and creative director
of Nervous System and a study co-author. "Because our approach is
algorithmic, it's possible to create customized networks for different
uses." After creating tissues patterned with these computationally
generated vascular architectures, the team demonstrated the seeding of endothelial cells inside the channels and focused on studying the survival
and function of cells grown in the surrounding tissue, including rodent
liver cells called hepatocytes. The hepatocyte experiments were conducted
in collaboration with University of Washington (UW) bioengineer and study co-author Kelly Stevens, whose research group specializes in studying
the delicate cells, which are notoriously difficult to maintain outside
the body.

"This method could be used with a much wider range of material cocktails
than many other bioprinting technologies," Stevens said. "This makes
it incredibly versatile." Miller said, "We showed that perfusion
through 3D vascular networks allows us to sustain these large liverlike 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."

========================================================================== Story Source: Materials provided by Rice_University. Note: Content may
be edited for style and length.


========================================================================== Journal Reference:
1. Ian S. Kinstlinger, Sarah H. Saxton, Gisele A. Calderon, Karen
Vasquez
Ruiz, David R. Yalacki, Palvasha R. Deme, Jessica E. Rosenkrantz,
Jesse D. Louis-Rosenberg, Fredrik Johansson, Kevin D. Janson,
Daniel W. Sazer, Saarang S. Panchavati, Karl-Dimiter Bissig,
Kelly R. Stevens, Jordan S.

Miller. Generation of model tissues with dendritic vascular networks
via sacrificial laser-sintered carbohydrate templates. Nature
Biomedical Engineering, 2020; DOI: 10.1038/s41551-020-0566-1 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/06/200629120203.htm

--- up 22 weeks, 6 days, 2 hours, 38 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1337:3/111)