Fight Aging!

Today, an update on the Vascular Tissue Challenge arrived in my in-box. It's been a year or so since the Methuselah Foundation and NASA jointly announced the Vascular Tissue Challenge, conducted as a part of the foundation's New Organ initiative. The challenge is a $500,000 research prize intended to draw greater attention to - and investment in - efforts that aim to surmount the greatest present roadblock in the field of tissue engineering: how to build tissues that contain the capillary networks required to sustain them. Natural tissues are packed with capillaries, hundreds passing through every square millimeter examined in cross-section. Reproducing this complexity in artificially grown tissues has proven to be very difficult. Yet other complex aspects of tissue growth have been solved: in the past few years, researchers have demonstrated themselves able to produce near fully functional organ tissues of many varieties. Unfortunately, since capillary networks are not yet a part of this picture, such solid tissue sections are limited in size to a few millimeters in their broadest dimension.

The goal of the New Organ initiative is the construction of patient-matched organs, as needed, from cell samples. To build any sizable tissue requires a life-like vascular network; there is no way around that. Given the impressive progress to date in every other aspect of tissue engineering required, however, it is fair to say that if the research community had a reliable solution for production of integrated blood vessel networks, then manufactured human organs would be only a few years distant. Thus initiatives like the Vascular Tissue Challenge are important; the creation of microscale blood vessel networks is the fulcrum for this field of medical research and development. Solve this challenge, and the first engineered organs are close.

Last June, the Methuselah Foundation and NASA officially launched the Vascular Tissue Challenge (VTC) at the White House Organ Summit, hosted by the Office of Science and Technology Policy. The VTC includes a $500,000 prize purse from NASA for the first teams that can successfully create 1cm or thicker vascularized tissues that remain functional and alive for more than 30 days. Along with this is the Center for the Advancement of Science in Space's (CASIS) "Innovations in Space Award," providing an additional $200,000 to support a research opportunity on board the International Space Station's National Laboratory. With the one year mark just behind us, we thought it was fitting to check in with the teams and see how they're doing. There's been a lot happening to advance these amazing bioengineering technologies over the last 12 months!

Since launching the Vascular Tissue Challenge, seven research organizations officially signed on to pursue the challenge of creating the thick, vascularized tissues required to win the $700,000 in awards along with the opportunity to pursue further research using the microgravity environment onboard the International Space Station. Each team is pursuing a different approach to creating vascularized tissues, and each has their own unique strategies and hurdles ahead. Here is a quick snapshot of what some of the teams have been doing and what they are planning for their next steps toward winning the Challenge before the sunset of the award at the end of 2019.

iTEAMS, Stanford University

Over the past year, iTEAMS has proposed and proved an integrated multi-scale, multi-modular system approach to overcome the challenges and tradeoff in functional vasculature requirements between major vascular lasting perfusion and capillary rapid sprouting and extensive coverage for diffusion. The former requires a slowly degradable biomaterial for sustained perfusion and the latter requires a fast biodegradable biomaterial for rapid sprouting and diffusion. The next steps being pursued are an optimization of perusable channel pathways, biomaterial candidates, and fabrication parameters. A critical upcoming milestone is to demonstrate functional microvasculature at a large scale for a long term in vitro. Team iTEAMS is working towards conducting their Vascular Tissue Challenge trials in 2018.

BioPrinter, Florida Institute of Technology

The team have developed a self-contained bioprinting system that is being used to generate tissue samples with high resolution and cell viability. They plan to use this printer to develop a sacrificial technique of bioprinting channels within a tissue sample. These channels will be used for the exchange of nutrients to cells needed to maintain viable tissue for an extended period of time. Currently, research is being conducted with various concentrations of bioink to obtain values that will result in high quality bioprinted tissue samples. In parallel, research on sacrificial techniques to create channels for nutrient flow is being conducted. The team anticipates that an official trial for the Vascular Tissue Challenge to be initiated in 2018.

Flow, Maize, and Blue, University of Michigan

The team has built a perfusion bioreactor that it is currently optimizing for customized tissue engineered vascular networks. The team hope to accomplish long-term perfusion of these vascular networks in the next 6 months with an official Vascular Tissue Challenge trial occurring sometime after that research is completed.

Techshot

Last summer, Techshot began formal efforts toward winning the Vascular Tissue Challenge by 3D printing biological materials and adult stem cells into vascular and cardiac structures on board a Zero Gravity Corporation aircraft. Test structures were printed during cycles of both zero G and high G forces, permitting evaluation of low viscosity, biological material printing in multiple gravity environments. As expected, the cycles of microgravity facilitated layer-by-layer printing of 3D structures with very low viscosities (these materials become puddles if printed on the ground). The team's next large step forward is a "Tissue Cassette" experiment that will be conducted this summer. Building upon last summer's work, Techshot will bioprint larger cardiac and vascular structures within a specialized container, a bioreactor they refer to as a "Tissue Cassette". This Tissue Cassette will not only provide an appropriate environment for culturing the 3D printed structure, it will impart physical and electrical cues to accelerate cell growth and tissue development. The bioreactor will also permit perfusion of the 3D bioprinted structure to further support cell growth in the larger printed volume.

The planned experiments will start by bioprinting identical sets of cardiac and vascular structures with an initial print size of 20mm x 30mm x 10mm. One set will stay on the ground. The second set will be loaded into a Techshot ADSEP system and launched to the International Space Station aboard SpaceX Cargo Dragon (CRS-12) on August 1, 2017. These experiments will provide insight into bioprinted cell behavior in microgravity and the associated differences in tissue development. This will provide a preliminary test of the technology Techshot plans to use for their Vascular Tissue Challenge trials that they expect to conduct after getting these results back.

Team Penn State, Pennsylvania State University

The team has made substantial progress with their research on micro-vascularization in engineered islets. In addition, the team has scaled up tissue constructs to a sub-cm^3 level and are working on expanding to the cm^3 level for the VTC trial. They have demonstrated viable vascularization with mouse cells and are currently conducting research to overcome technical issues with the co-culture of stem cell-derived human beta cells and microvascular endothelial cells. Finalizing the research to reach vascularization with these cells at the cm^3 level is the next critical step for this team, which they expect to take them into 2018 before conducting their final trials for the VTC.

Team WFIRM Bioprinting, Wake Forest University

During the past year, the WFIRM Bioprinting Team was focusing on the development of tissue-specific bioink systems that could mimic the microenvironments of each target tissues. The team assumes that these tissue-specific bioink systems can enhance the cell-cell and cell-matrix interactions that can accelerate tissue maturation/formation and functions. Up next in the team's research is to combine microvasculature created by endothelial cells with tissue-specific printed constructs. They plan to investigate the effects of endothelialized microvasculature on cell viability and tissue-specific functions of the tissue-specific printed constructs. It is not yet clear when the team's VTC trials will start, more will be known after their next research projects are completed.

Team Vital Organs, Rice University

At Rice University, Team Vital Organs is continuing to build out their 3D printing technology, characterizing the precision, cell viability and activity, designing assays for tissue assessment, and designing proper vascular architectures for complete tissue integration. Perfusion systems are complicated, but the team has a new large incubator that can now accommodate their proposed perfusion systems for the VTC. They are now working on validating long-term sterility and measurements from longitudinal assays. The team is looking forward to finishing these feasibility studies and putting together an official trial to win the Vascular Tissue Challenge within the next year.