Bioprinting for Regenerative Medicine


following up on my previous post (more than six years ago!)

Anthony Atala is a pediatric surgeon, urologist and directs the Wake Forest Institute for Regenerative Medicine (WFIRM) in North Carolina. Together with 400 colleagues and in a work that spans more than three decades, he has successfully implanted in human patients a variety of tissues regenerated from the patient’s own cells. Dr. Atala talked to about ways to translate the science of regenerative medicine into clinical therapy and the importance of adopting new technologies, as well as some of the challenges.

“Back in the 90’s we created by hand, even without using the printer, bladders, skin, cartilage, urethra, muscle and vaginal organs, and later implanted them successfully in patients. The printer automated what we were already doing and scaled it up making some of the processes easier. Still, the technology has its own challenges. With hand made constructs you have more control as you are creating the tissue, but with the printed structure everything has to be built in before it is created, so that you have to have the whole plan and information ready to go once you push that ‘start’ button”.

The WFIRM is working to grow tissues and organs and develop healing cell therapies for more than 40 different areas of the body, from kidney and trachea to cartilage and skin. Dr. Atala and his team of scientists have been first in the world to implant lab-grown tissues and organs into patients. Starting in 1990 with most of their research and implanting the first structures at the end of that decade, using a 3D printer to build a synthetic scaffold of a human bladder, which they then coated with cells taken from their patients. New research at WFIRM shows innovative wound healing through the use of a bedside 3D skin printer.

“Today, we continue to develop replacement tissues and organs, and are also working to speed up the availability of these treatments to patients. The ultimate goal is to create tissues for patients. Part of that is taking a very small piece of the patients tissue from the organ that we are trying to reconstruct, like muscle or blood vessels, only to expand the cells outside of the body and then use them to create the organ or structure along with a scaffold or a hydrogel which is the glue that holds the cells together. We have been doing this for quite some time with patients and 16 years ago we realized that we needed to scale up the technology and automate it to work with thousands of patients at a time, so we started thinking about 3D printers, and began using the typical desktop inkjet printer which was modified in-house to print cells into a 3D shape”.

The living cells were placed in the wells of the ink cartridge and the printer was programmed to print them in a certain order. The printer is now part of the permanent collection of the National Museum of Health and Medicine. According to Dr. Atala, all the printers at the WFIRM continue to be built in-house specifically to create tissues, so that they are highly specialized and able to create cells without damaging the tissue as it gets printed. Inside the institute, more than 400 scientists in the fields of biomedical and chemical engineering, cell and molecular biology, biochemistry, pharmacology, physiology, materials science, nanotechnology, genomics, proteomics, surgery and medicine work to try to develop some of the most advanced functional organs for their patients. At WFRIM they are focusing on personalized medicine, whereby the scientists use the sample tissue from the patient they are treating, grow it and implant it back to avoid rejection. Dr. Atala claims that “these technologies get tested extensively before they are implanted into a patient”, and that “it could take years or even decades of research and investigation before going from the experimental phase to the actual trial in humans. Our goal for the coming decade is to keep implanting tissues in patients, however, the most important thing for us is that we temper peoples expectations because these tissues come out very slowly and they come out one at a time, so we don’t give false hopes and provide the technology to patients who really need them. Working with over 40 different tissues and organs, means that about 10 applications of this technologies are already in patients. The research we have done helps us categorize tissues under order of complexity, so we know that flat structures (like skin) are the least complex; tubular structures (such as blood vessels) have the second level of complexity, and hollow non-tubular organs, including the bladder or stomach, have the third level of complexity because the architecture of the cells are manifold. Finally, the most complex organs are solid ones, like the heart, the liver and kidneys, which require more cells per centimeter”.

Human Cartilage can be 3D-printed

We’ve already discussed about the importance of cartilages in the human body. Two examples are the knee menisci and the thyroid cartilage that origins the Adam’s apple. We’ve also understood that 3D printing would probably represent a great revolution in the world of medicine, with the possibility of reproducing human body parts or fabricating new-generation assistive tools. Put the two things together and you’ll be able to print human cartilage by means of a 3D printer. I simply copy-paste here the content of this interesting webpage (to which all rights belong).

Dr. Darryl D’Lima and the members of his team at the Scripps Clinic in La Jolla, California, say they’ve unlocked the secrets of bioprinting human cartilage. That’s big news as the current best practice medical technique to replace lost cartilage is implantation of an artificial joint. Even though that sort of operation is painful, requires a long stretch of rehabilitation and artificial joints can often need replacement as time goes on, such procedures are the industry standard.

dr-darryl-dlima-bioprinting-cartilageThe global market for knee replacements amounts to nearly $7 billion annually, and experts say it will climb to nearly $11 billion within the next few years. Somewhere around 773,000 Americans have a hip or knee replaced each year. That’s big business and a lot of pain. But D’Lima says the design of his latest prototype bioprinter will print living cartilage, and that would mark a great leap forward for those suffering from painful knee and joint damage. Taking a Hewlett-Packard inkjet printer as his starting point, D’Lima says his bioprinter uses cartilage progenitor cells suspended in a biocompatible liquid. Once the solution is exposed to ultraviolet light, it takes a permanent shape.

cartilageThe extremely tiny drops of material provide other benefits as well. Measuring just one picoliter in diameter (or one-billionth of a liter), the droplets output by the bioprinter are compact enough to fill microscopic pits on the surface of cartilage or bone. “It would be the equivalent of filling a pothole,” D’Lima says. “It would automatically fill the defect as you’re printing it. You’re getting a fairly good mechanical integration into the tissue, which is very difficult for us to do when we do traditional transplants.”

Patients suffering with arthritis or  knee injuries are often plagued by a lack of cartilage. That means bones begin to grind against bones, and that means extreme pain and constant discomfort for patients. Using D’Lima’s bioprinting method, cartilage can be applied directly into the knee joint to provide a custom fit impossible to achieve by cutting pre-made cartilage to the particular patient. And one day, D’Lima says he’s confident that the process will involve printing the cartilage material directly onto a patient on the operating table. “We wouldn’t have to prepare (material) in advance,” D’Lima said. “All of this would be done on the day of surgery, on demand.”

knee-worn-cartThe major hurdle, according to D’Lima, is that as there’s currently no printer which can print directly onto a patient. His technique needs some refining. D’Lima says he’s working on those tweaks now with biotech firms Invetech and Organovo. And D’Lima also says he’s certain the method will work in practice as cartilage, due to its simpler cellular structure and lack of a complicated network of blood vessels, will be less challenging to create than some other tissues. Cartilage, flexible connective tissue found in various areas of the body, is not as rigid as bone but can be stiffer and less flexible than muscle. Composed of specialized cells called Chondrocytes, cartilage (unlike other connective tissues) doesn’t contain blood vessels. The chondrocytes are supplied with nutrients by diffusion as a result of the pumping action generated by compression, so in comparison with other connective tissues, cartilage grows and repairs much more slowly. “(Cartilage) is complex enough that you need technology like 3D printing, but at the same time, it’s not so complex that it’s extremely challenging,” he said. “We’ve gotten interest from other researchers, wanting to print retinal cells. The retina has some similarities to cartilage in that the photoreceptors and the neural cells of the retina don’t require a blood supply, so we don’t have to print microvasculature. And the retina is a mature tissue in that if you lose a photoreceptor, that’s it. You don’t grow a new one. So it’s fairly attractive for 3D printing.”

CORTEX 3D-printed cast

source: this website

cortex13D-printed casts for fractured bones could replace the usual bulky, itchy and smelly plaster or fibreglass ones in this conceptual project by Victoria University of Wellington graduate Jake Evill. The prototype Cortex cast is lightweight, ventilated, washable and thin enough to fit under a shirt sleeve.

A patient would have the bones x-rayed and the outside of the limb 3D-scanned. Computer software would then determine the optimum bespoke shape, with denser support focussed around the fracture itself. The polyamide pieces would be printed on-site and clip into place with fastenings that can’t be undone until the healing process is complete, when they would be taken off with tools at the hospital as normal. Unlike current casts, the materials could then be recycled.


Jake has just graduated from the Architecture and Design faculty at Victoria University of Wellington, with a Major in Media Design and a Minor in Industrial Design. After working with the orthopaedic department of his university on the project, he is now looking for backing to develop the idea further. “At the moment, 3D printing of the cast takes around three hours whereas a plaster cast is three to nine minutes, but requires 24-72 hours to be fully set,” says the designer. “With the improvement of 3D printing, we could see a big reduction in the time it takes to print in the future.”

cortex4After many centuries of splints and cumbersome plaster casts that have been the itchy and smelly bane of millions of children, adults and the aged alike, the world over, we at last bring fracture support into the twenty-first century.

The Cortex exoskeletal cast provides a highly technical and trauma-zone-localised support system that is fully ventilated, super light, shower friendly, hygienic, recyclable and even stylish!


other sources: one and two

3D-printing human body parts

In a previous post we saw how new technologies aim at printing human body parts by means of 3D printers. Recently, an amazing result has been achieved by some Doctors at the University of Michigan: they managed to print in 3D a tracheal splint for a 20-month-old patient in order to restore his bronchus functionality. This website offers the description of the surgical operation they performed, step by step.

Abstract – Tracheobronchomalacia in newborns, which manifests with dynamic airway collapse and respiratory insufficiency, is difficult to treat. In an infant with tracheobronchomalacia, we implanted a customized, bioresorbable tracheal splint, created with a computer-aided design based on a computed tomographic image of the patient’s airway and fabricated with the use of laser-based three-dimensional printing, to treat this life-threatening condition.

Description – At birth at 35 weeks’ gestation, the patient did not have respiratory distress and otherwise appeared to be in normal health. At 6 weeks of age, he had chest-wall retractions and difficulty feeding. By 2 months of age, his symptoms progressed and he required endotracheal intubation to sustain ventilation. The workup revealed the following:

  • an anomalous origin and malposition of the pulmonary arteries, with crisscross anatomy;
  • right pulmonary-artery hypoplasia;
  • compression of the left mainstem bronchus between an abnormally leftward-coursing ascending aorta and an anteriorly displaced descending aorta;
  • air trapping;
  • postobstructive pneumonia.

Despite placement of a tracheostomy tube, mechanical ventilation, and sedation, ventilation that was sufficient to prevent recurring cardiopulmonary arrests could not be maintained.


We reasoned that the localized tracheobronchomalacia was the cause of this physiological abnormality and made a custom-designed and custom-fabricated resorbable airway splint. Our bellowed topology design, similar to the hose of a vacuum cleaner, provides resistance against collapse while simultaneously allowing flexion, extension, and expansion with growth. The splint was manufactured from polycaprolactone with the use of a three-dimensional printer.


windpipeThe institutional review board of the University of Michigan consulted with the Food and Drug Administration and approved the use of the device under the emergency-use exemption, and written informed consent was provided by the patient’s parents. After transposition of the right pulmonary artery and failed aortopexy, sutures were placed around the circumference of the malacic left bronchus splintand tied through interstices of the splint, and the bronchus was expanded. Subsequent bronchoscopy revealed normal patency of the bronchus without dynamic collapse and normal ventilatory variation in the size of the left lung. The partial pressure of carbon dioxide in venous blood decreased from 88 to 48 mm Hg. Seven days after placement of the airway splint, weaning from mechanical ventilation was initiated, and 21 days after the procedure, ventilator support was discontinued entirely and the child was discharged home with the tracheostomy in place. One year after surgery, imaging and endoscopy showed a patent left mainstem bronchus . No unforeseen problems related to the splint have arisen. Full resorption of the splint was estimated to occur in 3 years.


This case shows that high-resolution imaging, computer-aided design, and biomaterial three-dimensional printing together can facilitate the creation of implantable devices for conditions that are anatomically specific for a given patient.

other sources: one and two