How 3D printing contributes to precision medicine

How 3D printing contributes to precision medicine

3D printing is profoundly shaping the future of medicine and healthcare. Researchers in the North combine artificial intelligence with state-of-the-art additive manufacturing technologies and develop bioresorbable materials and innovative bioprinting techniques to take precision medicine to the next level.

How has 3D printing developed from dentistry?

In dentistry, the 3D printing revolution is already routine:  patients benefit from individualized implants produced by additive manufacturing (AM) – or 3D printing – technologies. Many dental practices use their own 3D printers to manufacture dental crowns or bite splints. In the future, this technology will gradually move into clinics and enable the production of precise anatomical models and individualized surgical implants.  

Additive manufacturing expertise at Fraunhofer IMTE

“Nowadays, patients are well informed and demand the highest quality of care. They don’t want off-the-shelf products, which don’t fit their needs. I think that in the future, patients are no longer going to adapt to their treatment, the treatment is going to adapt to them,” predicts Thomas Friedrich, Head of Additive Manufacturing at the Fraunhofer Institution for Individualized and Cell-Based Medical Engineering (IMTE) in Lübeck.

Through a combination of their long-standing expertise in cell biology and AM, since 2020 researchers at the new institute have been working towards shaping the future of precision medicine by advancing medical products such as surgical implants. One area of focus that bridges these two competencies is research at the interface between implants and the body.

Thomas Friedrich is Head of Additive Manufacturing at the Fraunhofer Research Institution for Individualised and Cell-based Medical Engineering (IMTE) in Lübeck. © Thomas Friedrich
Thomas Friedrich is Head of Additive Manufacturing at the Fraunhofer Research Institution for Individualised and Cell-based Medical Engineering (IMTE) in Lübeck. © Thomas Friedrich

How is the longevity of implants improved?

“We want to understand how the surface of an implant, and its structure in particular, influence the ingrowth behavior of cells or the risk of rejection and infection. This research will help to improve the longevity of implants and reduce the need for a second operation,” summarizes Friedrich. AM technologies developed at Fraunhofer IMTE allow the surface of a material to be shaped on nanometer and micrometer scale, which is ideal when it comes to studying the growth of cells or organoids.

Fraunhofer IMTE and its partner, the University of Lübeck, accommodate more than twenty 3D printers, which mainly use polymers – or plastic – as a starting material. Some of these printers produce anatomical models for training medical professionals. These allow surgeons to practice challenging interventions such as the treatment of aneurysms or stroke in realistic environments, before moving on to patients.

Additional printers using titanium feedstock will soon be available to enhance the study of the surface properties of titanium implants. But researchers at IMTE also look further into the future when it comes to the most suitable implant materials: “I believe that one day, no patient will want to have a foreign body implanted, if an organic, living implant that integrates seamlessly into the body were available as an alternative,” says Friedrich.

Pills from the printer

A team of pharmacists of the hospital pharmacy at the University Medical Center Hamburg-Eppendorf (UKE) has developed a novel process for 3D printing of medication with individual, patient specific dosage. Michael Baehr, head of the UKE hospital pharmacy, explains the potential of this innovation:

“This process offers the possibility to manufacture drugs with a narrow therapeutic range individually while adjusting the required quantity and dosage. We are convinced that printing of medicines will make an important contribution to precision medicine and patient safety.” Together with UKE-informaticians the team is working on improvements that will allow automation and integration into the UKE’s existing digital medication process. In the future, AI might analyze movement patterns collected by wearables to calculate the individual dosage for patients with Parkinson’s. The project is funded by the EU with around 650,000 euros.

3D printing enables the production of customised, patient-specific dosages, e.g. for Parkinson's patients. © UKE Hamburg-Eppendorf
3D printing enables the production of customised, patient-specific dosages, e.g. for Parkinson’s patients. © UKE Hamburg-Eppendorf

What are the advantages of bioprinting?

Bioprinting is a budding technology that will take patient-specific implants to a completely new level. By using a patient’s living cells to manufacture 3D implants such as tissues or even organs, the risk of rejection can be minimized and the long wait for donor organs might eventually become a thing of the past. At Fraunhofer IMTE, researchers are currently developing tools for printing blood vessels.

Vascular surgeon Rouven Berndt from Kiel has already made major advances in this field. He and his team at University Hospital Schleswig-Holstein (UKSH) have developed a prototype of a 3D bioprinter to create fine blood vessels – only three to four millimeters in diameter – for use as bioartificial vessel or bypass implants.

What is the future prognosis for the implants?

Funded by a grant from the German Heart Research Foundation, the team has investigated how the printing process and mechanical properties of the material affect its suitability for the intended application. “We have recently submitted a publication in which we demonstrate that the vessels are durable and robust enough for use as bypass implants. For a first proof-of-concept, we are now testing their performance after implantation in animals. This will also help us to understand the biodegradability of the material in vivo,” summarizes Berndt.

The team has patented the bioprinting strategy and the production of its own bio-ink – a gel containing

  • brown alginate,
  • collagens,
  • elastin
  • and endothelial cells

– as well as the prototype of the printer. “Our next goal is industrialization of the process. Implementation according to industry standards will require a robotic platform, therefore we are currently in regular contact with a suitable industrial partner.”

In the future, the UKSH is going to further expand its research activities in the fields of bioprinting and tissue engineering: “Together with other research groups, we are planning to establish a core facility for tissue engineering and bioprinting to explore the opportunities for printing tissues and organs such as heart, kidney or bones,” explains Berndt.

A microrobot swims in a model of an artery. © Thomas Friedrich
A microrobot swims in a model of an artery. © Thomas Friedrich

Project DigiMed: Can bone implants be created by AI?

Artificial intelligence (AI) is gradually transforming the health care sector and combined with 3D printing, it might revolutionize the way patient-specific implants are produced. With experts in AM and AI working under one roof, the Fraunhofer Research Institution for Additive Manufacturing Technologies (IAPT) is the perfect place to merge both technologies.

In 2021, Fraunhofer IAPT researchers entered a collaboration with medical experts at the University Medical Center Hamburg Eppendorf (UKE) and Helmut Schmidt University (HSU), to develop an AI-based, fully automated process for designing and producing personalized implants. Their project DigiMed pursues three main goals: “With the use of AI algorithms, we want to speed up the production of 3D printed implants, while lowering costs and improving implant quality,” summarizes Phillip Gromzig, project leader of DigiMed at Fraunhofer IAPT.

DigiMed is already achieving initial successes

By now the team has significantly reduced production time for implants, which will save valuable time for accident victims: “Conventional 3D printed implants are designed manually and manufactured by external service providers who must ship the product to the clinic. By using AI, optimizing manufacturing, and combining all these processes under one roof, we have decreased production time from nine to three days,” summarizes Gromzig.

So far, the collaboration team has focused on the production of orbital implants. These wafer-thin titanium plates are used to treat injuries of the eye socket. In the future, many other bone injuries could be treated using the AI-based workflow developed at Fraunhofer IAPT, and the team has shown that it can be integrated in hospitals or enterprises. “We have demonstrated that the implants are safe and produced in line with the current Medical Device Regulation (MDR). However, legal barriers remain, as it is not yet certain who is liable should AI make a mistake,” says Gromzig.

How does DigiMed work?

Two AI-algorithms are at the heart of the DigiMed workflow: one analyzing CT scans of a patient’s anatomy and the other designing the virtual implant. “This technology could cause a paradigm shift in the production of personalized implants, with great added value for patients, whose time in hospital will be shortened significantly. Therefore, our next goal is to bring the workflow into the clinic,” adds Gromzig.

Patients are no longer going to adapt to their treatment, but the treatment is going to adapt to them.

Dr Thomas Friedrich
Head of Additive Manufacturing at Fraunhofer IMTE

Is magnesium the biomaterial of the future for 3D printing?

Further improvements for patients with bone injuries can be expected of research into highly innovative, bioresorbable implant materials like magnesium. Down the corridor at Fraunhofer IAPT, Kevin Janzen is working on a novel 3D printing process using magnesium alloys as a starting material. “Unlike titanium, magnesium has the advantage that it decomposes inside the body. Therefore, bone implants don’t have to be removed in a second operation,” explains Janzen. For project BioMag3D, the engineers optimize the process of sinter-based Additive Manufacturing of magnesium, in which printed parts undergo a heat treatment.

“One advantage of this technology is that it allows us to build hollow structures into the implant. These help us to control the rate of degradation and thereby aid the healing process,” adds the mechanical engineer. But using magnesium also has its downsides. Firstly, its chemical properties complicate 3D printing and secondly, hydrogen gas builds up as the implants decompose.

To tackle these issues, the Fraunhofer researchers are closely collaborating with engineers at the Helmholtz-Zentrum hereon in Geesthacht to optimize the properties of the feedstock. Within the next three years, the team will test the properties of their implants in petri dishes, before in vivo experiments take place. Janzen estimates that it will take at least ten years until the first 3D printed magnesium implants produced with this method enter the clinic: “Our technology is still very new, but we are in regular contact with medical staff at the UKE and the BG Hospital Hamburg to develop implants for the treatment of complicated bone fractures of the arm,” explains Janzen.

Text: Doreen Penso Dolfin

Featured image: © Thomas Friedrich

Further posts

HIV gene-editing therapy heads to the clinic

Business Nord|Innovation|Science & Translation HIV gene-editing therapy heads to the clinic

Provirex’ innovative genome editing therapy enables the elimination of persistent viral genomes from infected cells. The start-up is building a therapy hub in the future Science City Hamburg Bahrenfeld.

Stem cell medicine in the North: The report

Science & Translation Stem cell medicine in the North: The report

When the experts meet in Hamburg in July for the most important global congress in stem cell research – the ISSCR Annual Meeting – many regional players from the Life Science Nord cluster will also be there. A guide to the region's major players in research and industry in the stem cell field.

AI and crystals: “We provide the blueprint for innovative drug design”

Portrait AI and crystals: “We provide the blueprint for innovative drug design”

The start-up CrystalsFirst specializes in structural biological analyses of protein crystals for drug development. The team has been based at DESY in Hamburg-Bahrenfeld since 2022. In this interview, founder and CEO Serghei Glinca talks about the technology and the structural biology ecosystem in the North of Germany.