New developments in hardware and materials promise radical new bioprinting capabilities, particularly for medical applications.
Even the definition of the field and the terms it encompasses are expanding, explains Adam Jakus, Ph.D., co-founder and chief technology officer of advanced materials 3D printing company Dimension Inx.
“When the term bioprinting is used, it refers to printing living cells—which we also do—but more broadly, biomaterial printing can include printing living cells and printing materials that do not have live cells in them but can transform into living tissues after implantation. The primary reasoning is to create devices with geometries, architectures or designs that could not be made using traditional manufacturing,” he says.
While medical 3D printing is commonly thought of as producing materials for a specific patient, it also allows the creation of complex architectures that are biologically valuable. “For example, one of the most useful things we can 3D print out of our hyperelastic bone material is a simple rectangle, but that rectangle has an internal architecture that has three-dimensional porosity that could not be made using any traditional means of manufacturing,” Jakus says.
To get to that level of usefulness, engineers must first define the problem that needs solving—ideally in collaboration with end users. In the medical industry, surgeons are the end users, making them an important resource for this information. “Not enough engineers ever talk to surgeons,” Jakus says. “Very rarely do they actually talk to an end user.”
Think beyond the present
Another bit of advice for this rapidly advancing field: “Do not limit your design thinking to materials that already exist,” Jakus says. “Do not limit your design thinking to just maybe a shape or form factor. Keep your mind open to new materials even if they do not exist yet. They could exist in a month if you want them to. If you have the design criteria, someone can design them.”
Case in point: Although fixing cells on an object can be more easily performed by coating cells onto a fabricated, cell-free scaffold, bioprinting enables placing specific cells in specific positions for better end results. Because of this advantage, the industry is moving toward more robust bioprinting in the field of soft tissue regeneration and organ models.
“This is the reason pharmaceutical companies are moving toward the fabrication of organoids using bioprinting, which can far better mimic the response to their products than a simple 2D culture plate can,” says Carlos Carvalho, team leader, bioprinting department, at EnvisionTEC.
He points to research published in the field of nerve regeneration, cardiac tissue fabrication and faster healing cartilage implants using hybrid scaffolds (a mixture of strong thermoplastic cage with an interwoven hydrogel-cell scaffold). New drugs and cancer treatment approaches, such as tumor models, also can be designed with better-fabricated, reproducible models.
Aside from cell-laden hydrogels, bioprinters can produce implants using ceramic pastes, thermoplastic materials, silicones and photo-curable materials, as well as additives from biologically active materials through electrical conductive particles, to drugs to be released after implantation of the part.
Combining different materials into a single process is something that conventional methods cannot accomplish, according to Carvalho. Additionally, 3D printing enables complex geometries and interconnecting porosity within the fabricated implant, which is impossible with conventional manufacturing technologies.
As part of the biofabrication process, a patient’s defect area is scanned and biopsied to gather cells for cultivation. The part to be fabricated must be modeled and cells grown in sufficiently large quantities. Using the correct model, the correct material with the cells incorporated, the implant can be bioprinted. After printing, the printed cell-laden object is incubated in a bioreactor to control differentiation and start function of the printed cells. Then the fabricated part is implanted.
“Even when printing organoids or tumor models, the process does not deviate much,” Carvalho says. “This means that sterilization and regulatory issues must be kept in mind. Reproducibility of printing processes by using a reliable bioprinter and reliable sources for the biomaterials is vital.”
When assessing a bioprinting system, Carvalho advises that while some systems have an enclosure with a HEPA filter and positive pressure, their sterility is limited and user protection nonexistent. A bioprinter must be placed in a laminar flow hood bench, class II, type A or B for both product and user protection. Airflow around the printing platform should be conducted so that bacteria or other impurities cannot be blown from the rest of the machine onto the printed part. All pneumatic or mechanical components that contact the dispensed materials must be sterilizable.
Requirements should be set according to each application regarding printing accuracy, platform size, number and type of materials and overall machine reliability. If the same machine is used for more than bioprinting, consider requirements regarding system upgradeability. Carvalho recommends assessing the software integration of machine functions and their usability by contacting or visiting potential manufacturers directly.
Pairing the right technology with the right job is challenging. “In the field of tissue engineering, requirements constantly change and new technologies, like co-axial printing, are developed. A good communication between manufacturers and customers is vital to understand the needs and requirements for the next bioprinter developments,” Carvalho says.
Engineers should educate themselves through any and all resources available to them, including through ASME. It currently offers a Design for Additive Manufacturing with Metals course, and the first AM Medical event will be occurring in May 2020 in Minneapolis.