AMS Spring 2023

AMS Speaker Spotlight: Analyzing the Market for Smart Bioinks

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One of the largest barriers to producing new bioprinting applications is creating and refining the advanced bioinks required for printing human tissue models. For example, consider the use of 3D printed hip replacements. For this application, inert materials such as titanium may be a suitable option. However, titanium would not promote cell growth into the material post-printing. Bio-inks are a unique subset of 3D printing materials where the host material acts as a suitable growth medium for the living cells seeded inside.  Numerous factors go into the development of a novel bio-ink depending on the cells being used and the tissue that is emulated. “The selection of materials has a great impact on the biocompatibility, cellular viability, and mechanical behaviour of a bioprinted structure and thus care must be taken when determining the most suitable bioink for a given tissue engineering application.“ (Maan et al., 2021, para. 8). Smart Bioinks for the Printing of Human Tissue Models goes into further detail on the current state and progress of smart bioinks.

Limitations when printing biomaterials:

Extrusion-based bioprinters use heat and pressure to deposit material onto the build surface. When printing with cells, small increases in either can induce cell death, resulting in non-viable structures. Low viscosity materials with shear-thinning properties reduce the damage to cells but have difficulties maintaining shape while printing.

Printing with the Cellink BioX™, an extrusion-based bioprinter. Axolotl Biosciences, 2022.

Printing with the Cellink BioX™, an extrusion-based bioprinter. Axolotl Biosciences, 2022.

Light-based bioprinters require specific concentrations of UV blockers and photoinitiators, which are toxic to cells. Reducing concentrations is beneficial for cell viability, but also reduces the quality of prints and will cause print failures. The key to bioink development is balancing these factors according to the target application. There exists a need for a wide range of printable biomaterials, with some being more specialized than others. Axolotl Bioscience’s TissuePrint is one such material, made to print a variety of cell lines including Human Induced Pluripotent Stem Cells (hiPSC’s), Neural Progenitor Cells (NPC’s), and Mesenchymal Stem Cells (MSC’s). New bioinks are in the works that will support different cell lines and drug delivery systems.

Disease Modeling:

The discovery of hiPSC’s in 2007 was a large leap forward in the field of regenerative medicine. Somatic cells could now be reprogrammed into a pluripotent state and be used to produce any tissue in the human body. These cells can be taken directly from a patient to create personalized bioprinted tissue models, used to study the biology of diseases, or as a tool for screening potential drug treatments. Bioprinting neural tissues using stem cells as a tool for screening drug targets for Alzheimer’s disease discusses one such application, where NPC’s are derived from Alzheimer’s patients and incorporated into bioink. 3D constructs can then be created to study disease progression and the effect of different medications on patients.

Glioblastoma multiforme (GBM) is a type of brain cancer to which current treatments have been minimally effective, creating a need for new treatment options and efficient ways to test them. Animal tissue has been limiting in both the cost of acquisition and time constraints associated with sourcing them. 2D structures are often more viable but fail to replicate the advanced structures found in 3D tumor growth. 3D printed constructs can be used as an effective tool in pre-clinical trials and accelerate the development of new treatment options. Novel N-cadherin antagonist causes glioblastoma cell death in a 3D bioprinted co-culture model, shows this in action with a promising anti-cancer agent preventing spheroid growth and inducing cell death for GBM.

Similar possibilities have been shown with Parkinson’s, a degenerative disorder that affects the central nervous system. Advancements in smart bioinks are opening doors for notoriously difficult to manage diseases. In the future, 3D printed constructs could play a significant role in the adoption and trials of new medications.

3D bioprinting constructs as a tool for evaluating surgical equipment and procedures:

Artificial ureter produced with Gelatin/Collagen based biomaterial. Axolotl Biosciences, 2021.

Bioprinted constructs can serve as a valuable tool for assessing the performance of surgical equipment, and for surgeons to practice their skills in a controlled environment. Mock ureters were created with Alginate, Gelatin, and Collagen and were used to test the viability of surgical lasers and the unintended damage they may cause. Different concentrations of each reagent change the structural properties of the final material. Varying the thickness, rigidity, and width of the extruded cylinders allows them to replicate bronchi, the trachea, and other parts of the human body. Although initial testing is done without cells, these materials are capable of sustaining cell growth which offers more precise measurements of cell death and tissue damage. Animal organs can and have been used for this type of testing but bioprinting allows for precise tuning of the dimensions and properties of the organs while being more sustainable to procure.

3D bioprinting structures to evaluate biomaterials for treating spinal cord injury:

Spinal cord injuries have been a difficult area to study with the complexity of the nervous system and scale of the spinal cord. The recently announced “Mend the Gap” project aims to regenerate nerve fibers in spinal cord injuries and restore some functionality. Modeling the spinal cord for testing requires a level of detail that is not possible on extrusion printers, creating optically transparent parts makes this task even more difficult. Instead, a photopolymerized biomaterial called PEGDA is used to create a soft, hollow structure that is then filled with artificial cerebral-spinal fluid. The constructs are only a few millimeters in diameter and provide a test bench for spinal cord injections. The injections consist of magnetically aligned components suspended in a biomaterial. Unlike animal testing, the spinal cord phantoms can be viewed through microscopes and created in bulk with precise sizing. Because of this, each test can be consistently replicated while minimizing the waste of the injectable material. This also allows factors such as the orientation of the magnetic components to be determined.

PEGDA-based spinal cord phantoms, printed on the Cellink LumenX™. Axolotl Biosciences, 2021.

Advancements in materials and printing methods, such as the use of suspension media for support and more cell-viable bio-inks will continue to expand the markets for biomaterials. Additionally, steady changes to regulatory bodies will allow pharmaceutical companies to better utilize bioprinting for pre-clinical testing.

Dr. Stephanie Willerth, CEO of Axolotl Biosciences, will further discuss markets for printable biomaterials at the upcoming Additive Manufacturing Strategies 2022 summit, Panel 3: Markets for printable biomaterials. More information can be found at additivemanufacturingstrategies.com and axolotlbiosciences.com.

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