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Constructing living tissues

Hope from 3D printing

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Demand for human tissue is enormous. As a result, great hope is now being placed on computer-controlled “bio-printers”. In particular, considerable progress is being made with tissues that do not depend on capillaries and nerves.

Dr. Klaus Duffner | Germany

“The number of people desperately awaiting organ transplants by far exceeds the number of available donor organs”, says Dr. Anthony Atala, Director of the Wake Forest Institute for Regenerative Medicine in Winston Salem, North Carolina.1 “Every day 21 US citizens fall victim to there being no such organ available to them. To rectify this shortfall, many research teams are currently endeavoring to construct living tissue with 3D printers.”

First bio-printer at the turn of the millennium

In the mid 1980’s the US American Charles W. Hull developed a printer that enabled 3D objects to be manufactured under the control of special “computer aided design” (CAD) software.2,3 At first the materials used were chiefly polymers, then, as of the beginning of the 90’s, nanocomposites, blended plastics and powdered metals. It was not long before medical researchers also turned their attention to this development: If a solid plaster or plastic ornament could be manufactured using a printer, should it not be possible to print a living organ? In 1999 scientists at the Wake Forest Institute used a 3D printer for the first to manufacture a scaffold for a human bladder. They coated the modeled scaffold with cells from their patients. Other groups followed by printing the first miniature kidneys in 2002 and the first blood vessels in 2010. 

Like an inkjet printer

The operation of a bio-printer mirrors the operation of a normal 3D printer. A computer controls extruders that construct desired structures from a polymer gel. Using a 3D model, spray nozzles extrude a cellular suspension in the form of tiny droplets. The gel is usually based on an alginate composite. Every droplet deposited contains several thousand cells capable of regeneration. These cells are collected in advance by biopsy from the organ to be replaced and then multiplied in a liquid nutrient medium containing oxygen. Experiments have also been conducted with adult or induced pluripotent stem cells (e.g., from bone marrow). With appropriate growth factors designated by the researchers and by defining both viscosity and temperature of the matrix exactly, researchers encourage cells to organize themselves into functional tissue.

Research in full swing

Scientists throughout the world are currently working on methods for tissue-engineering human organs using 3D printers. Most models, however, are still on the drawing board. In particular, building functional organs that rely on nutrient blood vessels and nerves is still a pipe dream in the view of researchers like Simon Hoerstrup, the Director of the Institute for Regenerative Medicine at the University of Zurich, where polymer scaffolds are subsequently coated with the patients’ own cells using a 3D printer.4 In children with serious congenital heart defects, Dr. Hoerstrup intends to implant living, i.e., growing, heart valves after birth. What he has already shown can work in animal experiments on lambs is soon to be studied in the clinic with human babies. The development of less complex tissues like heart valves, blood vessels and cartilage that do not need a direct supply of blood nutrient is already well ahead. For example, Swedish researchers recently made cartilage consisting of a new hydrogel biomaterial and human cells, which grew successfully in mouse skin.5

Meanwhile, a team of researchers at the University of California in San Diego (UCSD) was successful using a 3D printer to manufacture a small, functional system of blood vessels and implant it into live mice.6 And a new hydrogel made from alginate, polyvinyl alcohol and hydroxyapatite was recently developed by scientists led by Stephanie T. Bendtsen at the Institute for Material Sciences, University of Connecticut. The alginate is designed to improve the properties of bones “printed” using 3D printers.7 Finally, victims of serious burns and animal testing for cosmetics and drugs could benefit from a bilayer human skin sourced from a 3D printer. A bio-ink for the printer cartridges containing blood plasma, fibroblasts and keratinocytes was developed by Spanish scientists, and the resulting bilayer skin grew without difficulty when implanted in mice.

New ears

Using an experimental technique at the end of last year, Chinese researchers created a new ear by an unusual means.9 The patient lost an ear that had been damaged irreparably in a car accident. Dr. Wang Jihua, Director of Plastic Surgery at the Kunming Medical Second Hospital, printed a model of an ear using a 3D printer and fashioned a new ear out of rib cartilage. This model was then implanted under the skin of the patient’s arm, so it could continue to grow for subsequent transplant onto the patient’s head. Doctors are also currently using 3D printing techniques in Edinburgh, Scotland to make a new ear for a nine year old girl afflicted by a congenital ear muscle abnormality. Using a 3D printer, researchers created a mirror image of the normal ear out of plastic and used this template to model a new ear from rib cartilage. Initial surgery entailed the plastic ear being attached to the head beneath the skin in order to create the site and structure for the new ear. As soon as the skin has adapted, a second operation will allow the replacement ear to be attached in the desired position.

Be it ears, heart valves, skin, bone, kidneys or other tissues: 3D technology could soon open up a new era in medicine.

Dr. Klaus Duffner

Dr. Klaus Duffner | Germany

Scientific Journalist
Medizin & Wissen Freiburg

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