Working on Methods of Generating Blood Vessel Networks in Engineered Tissue

Perhaps the greatest technical challenge in tissue engineering is the matter of blood vessels. The cells in any tissue larger than a sliver must be supported by a network of capillaries and larger blood vessels, and putting those in place isn't a simple undertaking. This is one of the principal reasons why decellularization is such an attractive option for engineering organs and large tissue sections: the decellularized donor organ provides a scaffolding of blood vessel networks and other structures, along with chemical cues necessary to guide the right cells to the right places.

Reproducing these intricacies in sufficient detail from scratch is currently beyond the capabilities of the scientific community, but people are working on it. Over the next decade, we should expect to see increasingly sophisticated, competing efforts to produce complex scaffolds and structure in tissue engineering. More importantly there will be efforts to make this a reliable and low-cost process - scalable infrastructure is the more important part of the equation here. This is all taking place right now and has been for years; progress is being made, as this is a comparatively well-funded field.

3-D printing technologies show a great deal of promise for tissue engineering, as there is already a large and mature industry devoted to modeling and printing detailed structures in various materials. Companies such as Organovo have made inroads in this area over the past decade, but there is a great deal of work yet to accomplish. These are still the early days for tissue printing. To pick an example of the present state of the art, this recent article looks at one research group and their approach to generating blood vessel networks in bioprinted tissues. As it notes, the near term goal is not tissues for transplantation, but to obtain a result that is sufficiently close to the real thing for use in drug and toxicity testing:

An essential step toward printing living tissues

A new bioprinting method [creates] intricately patterned, three-dimensional tissue constructs with multiple types of cells and tiny blood vessels. The work represents a major step toward a longstanding goal of tissue engineers: creating human tissue constructs realistic enough to test drug safety and effectiveness. To print 3D tissue constructs with a predefined pattern, the researchers needed functional inks with useful biological properties, so they developed several "bio-inks" - tissue-friendly inks containing key ingredients of living tissues. One ink contained extracellular matrix, the biological material that knits cells into tissues. A second ink contained both extracellular matrix and living cells.

To create blood vessels, they developed a third ink with an unusual property: it melts as it cools, rather than as it warms. This allowed the scientists to first print an interconnected network of filaments, then melt them by chilling the material and suction the liquid out to create a network of hollow tubes, or vessels.

[The] team then road-tested the method to assess its power and versatility. They printed 3D tissue constructs with a variety of architectures, culminating in an intricately patterned construct containing blood vessels and three different types of cells - a structure approaching the complexity of solid tissues. Moreover, when they injected human endothelial cells into the vascular network, those cells regrew the blood-vessel lining. Keeping cells alive and growing in the tissue construct represents an important step toward printing human tissues. "Ideally, we want biology to do as much of the job of as possible."


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