Germany-based Zellwerk GmbH is using single-use bioreactors provided by the rapid injection moulded parts service from Protolabs®, to help combat cancer in patients where vital immune cells are deficient. Made from special plastic resin with carefully controlled surface finish properties, this ground breaking system has opened up completely new perspectives in the world of regenerative medicine.
When it comes to the war on cancer, the body has its own front guard: ‘Natural killer cells’ are able to destroy their cancer cell rivals and prevent viral infections from spreading. Unfortunately, the immune system in many patients is already weakened to such an extent that it cannot produce enough of these precious cells.
Now however, Zellwerk GmbH of Eichstaedt, some 25km northwest of Berlin, has succeeded in cultivating cells outside the human body in greater quantities than ever previously achieved. Zellwerk, a specialist in cell culture and tissue engineering, performs the task using single-use bioreactors manufactured using injection moulded components supplied by Protolabs.
Prof. Dr. Hans Hoffmeister, CEO of Zell GmbH, describes the system while holding an inconspicuous, transparent plastic part with a lid in his hands. "What you see here is the core of our bioreactors. It meets all the requirements necessary to produce the body's own cells in the same quantity as drugs, in a standardised and repeatable process,” he says.
"This patented system is both a revelation in regenerative medicine and the dream of biomedical scientists. It takes a sample from the patient such as blood, isolates the immune cells, cultures them outside the body in large quantities, and leads them back to fight tumour cells.”
The Zell system is called Z® RP Technology and comprises an incubator, located in the sterile work chamber of the bioreactor, and a special adapter. An external control unit monitors, controls and documents all of the parameters.
"It is critical that ‘laminar flow’ is created in the plastic reactor," says Prof. Dr. Hoffmeister. “The cells are placed on the bottom of the reactor and flushed evenly without creating turbulence. Simultaneously, cells with oxygen and fresh medium are supplied, while spent media is transported and a constant pH maintained.”
To ensure the repeatability of the process, the vital element of the challenge was to create a special surface in the reactor offering the optimum amount of friction – not too smooth and not too rough. Construction Manager Rainer Mausolf summarises the requirements for the reactor resin and its surface condition: "The choice of plastic was crucial because we needed to provide constant chemical and physical conditions in the reactor. We tried several common plastics but had difficulty in finding a material that was resistant to sterilisation by gamma-rays. Finally, with the help of Protolabs, we found the optimum resin for our system,” he says.
“Protolabs also helped extensively with the implementation of our surface requirements. In Z® RP Technology systems the cells must not be free to be rinsed around and therefore require a finely grained surface on which they find support. Only this makes it possible to have a standard, repeatable process. To keep the conditions uniform throughout the system we have a probe upstream of the reactor adapter that continuously measures the pH, temperature and oxygen, and relays this data to an external control unit."
All the bioreactors and probe adapters (in different versions) used in Z RP Technology are manufactured using the Proto Labs' rapid injection-moulded parts service.
“At first we could not believe the speed and reliability of the service,” says Mr. Mausolf. “We knew of no other suppliers who could deliver finished parts within 10 days of transferring the 3D model. Sometimes we would even receive components within five days, if we had opted for this. The process was so simple: I just uploaded my 3D SolidWorks model to the Protolabs website. Almost immediately my quote arrived and shortly after I was contacted with valuable tips on implementation. Within days we had received the first reactors and adapters made using our special plastic.”
Prof. Dr. Hoffmeister adds: "For Zellwerk this is both the most ideal and least expensive solution. We absolutely rely on parts made of ‘real’ material. Substitute materials, such as those offered by traditional prototype methods are useless for us. Without Protolabs, we would have never made as quickly and inexpensively a fully functional bioreactor for growth of the body's own immune cells that meets the stringent requirements of regulatory agencies."
Z RP Technology bioreactors from Zellwerk now represent the most advanced cultivation technology commercially available for adherent cell types and tissue engineering purposes.