Tag Archives: Anthony Atala

Feasibility of printing ear, bone, and muscle structures

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Over ten years ago I attended a show at the Vancouver (Canada) Art Gallery titled ‘Massive Change’ where I saw part of a nose or ear being grown in a petri dish (the work was from an Israeli laboratory) and that was my introduction to tissue engineering. For anyone who’s been following the tissue engineering story, 3D printers have sped up the growth process considerably. More recently, researchers at Wake Forest Baptist Medical Center (North Carolina, US) have announced another step forward for growing organs and body parts, from a Feb. 15, 2016 Wake Forest Baptist Medical Center news release on EurekAlert,

Using a sophisticated, custom-designed 3D printer, regenerative medicine scientists at Wake Forest Baptist Medical Center have proved that it is feasible to print living tissue structures to replace injured or diseased tissue in patients.

Reporting in Nature Biotechnology, the scientists said they printed ear, bone and muscle structures. When implanted in animals, the structures matured into functional tissue and developed a system of blood vessels. Most importantly, these early results indicate that the structures have the right size, strength and function for use in humans.

“This novel tissue and organ printer is an important advance in our quest to make replacement tissue for patients,” said Anthony Atala, M.D., director of the Wake Forest Institute for Regenerative Medicine (WFIRM) and senior author on the study. “It can fabricate stable, human-scale tissue of any shape. With further development, this technology could potentially be used to print living tissue and organ structures for surgical implantation.”

With funding from the Armed Forces Institute of Regenerative Medicine, a federally funded effort to apply regenerative medicine to battlefield injuries, Atala’s team aims to implant bioprinted muscle, cartilage and bone in patients in the future.

Tissue engineering is a science that aims to grow replacement tissues and organs in the laboratory to help solve the shortage of donated tissue available for transplants. The precision of 3D printing makes it a promising method for replicating the body’s complex tissues and organs. However, current printers based on jetting, extrusion and laser-induced forward transfer cannot produce structures with sufficient size or strength to implant in the body.

The Integrated Tissue and Organ Printing System (ITOP), developed over a 10-year period by scientists at the Institute for Regenerative Medicine, overcomes these challenges. The system deposits both bio-degradable, plastic-like materials to form the tissue “shape” and water-based gels that contain the cells. In addition, a strong, temporary outer structure is formed. The printing process does not harm the cells.

A major challenge of tissue engineering is ensuring that implanted structures live long enough to integrate with the body. The Wake Forest Baptist scientists addressed this in two ways. They optimized the water-based “ink” that holds the cells so that it promotes cell health and growth and they printed a lattice of micro-channels throughout the structures. These channels allow nutrients and oxygen from the body to diffuse into the structures and keep them live while they develop a system of blood vessels.

It has been previously shown that tissue structures without ready-made blood vessels must be smaller than 200 microns (0.007 inches) for cells to survive. In these studies, a baby-sized ear structure (1.5 inches) survived and showed signs of vascularization at one and two months after implantation.

“Our results indicate that the bio-ink combination we used, combined with the micro-channels, provides the right environment to keep the cells alive and to support cell and tissue growth,” said Atala.

Another advantage of the ITOP system is its ability to use data from CT and MRI scans to “tailor-make” tissue for patients. For a patient missing an ear, for example, the system could print a matching structure.

Several proof-of-concept experiments demonstrated the capabilities of ITOP. To show that ITOP can generate complex 3D structures, printed, human-sized external ears were implanted under the skin of mice. Two months later, the shape of the implanted ear was well-maintained and cartilage tissue and blood vessels had formed.

To demonstrate the ITOP can generate organized soft tissue structures, printed muscle tissue was implanted in rats. After two weeks, tests confirmed that the muscle was robust enough to maintain its structural characteristics, become vascularized and induce nerve formation.

And, to show that construction of a human-sized bone structure, jaw bone fragments were printed using human stem cells. The fragments were the size and shape needed for facial reconstruction in humans. To study the maturation of bioprinted bone in the body, printed segments of skull bone were implanted in rats. After five months, the bioprinted structures had formed vascularized bone tissue.

Ongoing studies will measure longer-term outcomes.

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The research was supported, in part, by grants from the Armed Forces Institute of Regenerative Medicine (W81XWH-08-2-0032), the Telemedicine and Advanced Technology Research Center at the U.S. Army Medical Research and Material Command (W81XWH-07-1-0718) and the Defense Threat Reduction Agency (N66001-13-C-2027).

(Sometimes the information about the funding agencies is almost as interesting as the research.) Here’s a link to and a citation for the paper,

A 3D bioprinting system to produce human-scale tissue constructs with structural integrity by Hyun-Wook Kang, Sang Jin Lee, In Kap Ko, Carlos Kengla, James J Yoo, & Anthony Atala. Nature Biotechnology (2016)  doi:10.1038/nbt.3413 Published online 15 February 2016

This paper is behind a paywall.

As you can see, despite being printed, this latest ear is also spending time in a dish,

WakeBaptistEar

Courtesy: Wake Forest Baptist Medical Center

Printing new knee cartilage

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I was reminded of the 1992 Olympics in Barcelona while reading the Nov. 22, 2012 news item on Nanowerk about printing cartilage for knees. Some years ago I knew a Canadian wrestler who’d participated in those games and he had a story about knee cartilage that featured amputation.

Apparently, wrestlers in earlier generations had knee surgeries that involved removal of cartilage for therapeutic purposes. Unfortunately, decades later, these retired wrestlers found that whatever cartilage had remained was now worn through and bones were grinding on bones causing such pain that more than one wrestler agreed to amputation. I never did check out the story but it rang true largely because I’d come across a similar story from a physiotherapist regarding  a shoulder joint and the consequences of losing cartilage in there (very, very painful).

It seems that scientists are now working on a solution for those of us unlucky enough to have damaged or worn through cartilage in our joints, from the Nov. 22, 2012 IOP science news release, (Institute of Physics) which originated the news item,

The printing of 3D tissue has taken a major step forward with the creation of a novel hybrid printer that simplifies the process of creating implantable cartilage.

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The printer is a combination of two low-cost fabrication techniques: a traditional ink jet printer and an electrospinning machine. Combining these systems allowed the scientists to build a structure made from natural and synthetic materials. …

In this study, the hybrid system produced cartilage constructs with increased mechanical stability compared to those created by an ink jet printer using gel material alone. The constructs were also shown to maintain their functional characteristics in the laboratory and a real-life system.

The key to this was the use of the electrospinning machine, which uses an electrical current to generate very fine fibres from a polymer solution. Electrospinning allows the composition of polymers to be easily controlled and therefore produces porous structures that encourage cells to integrate into surrounding tissue.

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In this study, flexible mats of electrospun synthetic polymer were combined, layer-by-layer, with a solution of cartilage cells from a rabbit ear that were deposited using the traditional ink jet printer. The constructs were square with a 10cm diagonal and a 0.4mm thickness.

The researchers tested their strength by loading them with variable weights and, after one week, tested to see if the cartilage cells were still alive.

The constructs were also inserted into mice for two, four and eight weeks to see how they performed in a real life system. After eight weeks of implantation, the constructs appeared to have developed the structures and properties that are typical of elastic cartilage, demonstrating their potential for insertion into a patient.

The researchers state that in a future scenario, cartilage constructs could be clinically applied by using an MRI scan of a body part, such as the knee, as a blueprint for creating a matching construct. A careful selection of scaffold material for each patient’s construct would allow the implant to withstand mechanical forces while encouraging new cartilage to organise and fill the defect.

The researchers’ article in the IOP science jouBiofrarnal, Biofabrication, is freely available for 30 days after its date of publication, Nov. 21, 2012. You do need to register with IOP science to gain access. Here’s the citation and a link,

Hybrid printing of mechanically and biologically improved constructs for cartilage tissue engineering applications by Tao Xu, Kyle W Binder, Mohammad Z Albanna, Dennis Dice, Weixin Zhao, James J Yoo and Anthony Atala in 2013 Biofabrication 5 015001 doi:10.1088/1758-5082/5/1/015001

I believe all of the scientists involved in this bioprinting project are with the Wake Forest Institute for Regenerative Medicine.