Mar 8, 2016 | By Alec

3D bioprinting, of course, is something of a holy grail in the 3D printing world. Though practical applications are still a few years away, the futuristic concept of creating 3D implantable blood vessels, skin tissue and even complete organs is every futurist’s dream. Applications in the field of regenerative medicine are also potentially possible. It’s therefore hardly surprising that several research teams throughout the world are working on 3D bioprinting, and a team from Harvard’s School for Engineering and Applied Sciences(SEAS) and the Wyss Institute for Biologically Inspired Engineering have just made a major breakthrough. They have developed a new method for scaling up tissue engineering through the 3D printing of thick vascularized tissue constructs, complete with stem cells, extracellular matrix and circulatory channels.

This fascinating new technique, which essentially makes networks of vasculature that enable fluids, nutrients and cell growth to penetrate the complete tissue, could be the breakthrough we are waiting for. It is being reported on in the latest edition of the journal Proceedings of the National Academy of Sciences. Hansörg Wyss Professor of Biologically Inspired Engineering Jennifer A. Lewis is the senior author on the study, while her team also includes graduate researcher David Kolesky and researchers Kimberly Homan and Mark Skylar-Scott.

As professor Lewis explains, this breakthrough adds a whole new dimension to 3D bioprinting. “This latest work extends the capabilities of our multi-material bioprinting platform to thick human tissues, bringing us one step closer to creating architectures for tissue repair and regeneration,” she says. Most 3D bioprinting techniques aren’t very suitable for anything more than small prints, and creating larger, robust vascular networks that can actually sustain tissue life has been one of the main challenges for the field. But with this breakthrough, Lewis and her team have increased the tissue thickness threshold by up to tenfold (up to one centimeter thick tissue).

Essentially, they found a way to create a 3D printed structure packed with living cells, an extracellular matrix and the plumbing needed to sustain that as part of human tissue – so for, for up to six weeks. In their study, this method is tested with tissue containing human bone marrow stem cells. By pumping bone growth factors through their vasculature – lined with the same endothelial cells we have in our blood vessels – they were actually able to induce cell development for about the course of a month.

So how is their 3D bioprinting method different from others? In a nutshell, they are using a customizable, 3D printed silicone mold as a housing and plumbing system. As you can see in the clip below, a grid of vascular channels are 3D printed into that mold, over which stem cell ink is printed. Those inks are actually self-supporting and strong enough to hold shape when subsequent layers are added. Through this method, vertical vascular pillars are 3D printed at the intersections of the vascular grid, which form a network of microvessels throughout the tissue. The open gaps in the remarkable tissue are filled with a liquid composed of fibroblasts and extracellular matrix. The result is a soft tissue structure with blood vessels. Hooked onto an inlet and an outlet, nutrients are pumped through the structure, just like our body does for our tissue.

Theoretically, a variety of tissues can be created with this method. The type of growth factors delivered to the cells subsequently determines cell differentiation, and the shape of the 3D printed silicone mold can be altered to change the structure and composition of the tissue. “Having the vasculature pre-fabricated within the tissue allows enhanced cell functionality at the deep core of the tissue, and gives us the ability to modulate those cell functions through the use of perfusable substances such as growth factors,” David Kolesky explained on Harvard’s website.

It is thus definitely a breakthrough, but one that will lead to subsequent breakthroughs and not just yet to 3D printed organs. “This research will help to establish the fundamental scientific understanding required for bioprinting of vascularized living tissues,” said Zhijian Pei, the National Science Foundation Program Director for the Directorate for Engineering Division of Civil, Mechanical and Manufacturing Innovation that funded the project. “Research such as this enables broader use of 3-D human tissues for drug safety and toxicity screening and, ultimately, for tissue repair and regeneration.”

Donald Ingber, the Judah Folkman Professor of Vascular Biology at Harvard’s Medical school even went as far as calling this new technique a paradigm shifting breakthrough. “Their ability to build living 3D vascularized tissues from the bottom-up provides a potential way to form macroscale functional tissue replacements that can be surgically connected to the body’s own blood vessels to provide immediate perfusion of these artificial tissues, and thus, greatly increase their likelihood of survival.  This would overcome many of the problems that held back tissue engineering from clinical success in the past,” he said of the innovative technique. Could this be the solution the field of 3D bioprinting needs?

 

 

Posted in 3D Printing Technology

 

 

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