3D Bioprinting: A Solution To The Organ Shortage Crisis?

Source

But what if we could skip the whole process? What if we no longer had to harvest organs from people? What if we could make on-demand organs with a patient’s own cells?

Similar to 3D printing, bioprinting is an additive manufacturing approach in which three-dimensional objects are built from a computer-aided design (CAD) or digital 3D model. But unlike 3D printing, bioprinters print with cells and biomaterials, creating organ-like structures that allow living cells to multiply.

  1. Bioprinting: Researchers then load the cell-laden bioink into a cartridge and choose one or multiple print heads depending on the desired construct. Developing different types of tissue requires researchers to use different types of cells, bioinks, and equipment.
  2. Post-bioprinting: To create stable structures for the biological material, printed parts usually undergo mechanical and chemical stimulation. Finally, the cell-laden constructs are placed inside an incubator or bioreactor for cultivation.
  • During 3D modeling, a blueprint is generated in high detail. Using CAD software, the blueprint may include layer-by-layer instructions for the bioprinter. Fine adjustments may be made at this stage to avoid the transfer of defects.
  • The process of bioink preparation combines living cells with a biomaterial, such as collagen, gelatin, hyaluronan, silk, alginate, or nanocellulose. Bioink provides the cells with the nutrients to survive and a scaffold on which they can grow. The complete substance is patient-based and function-specific.
  • 3D printing consists of depositing the bioink layer by layer, each having a thickness of 0.5 mm or less. The number of nozzles and the type of desired tissue determine the amount of deposit dispensed.
  • Finally, during solidification, the viscous liquid starts to hold its shape as more layers are continuously deposited. The process of blending and solidification is known as crosslinking and may be aided by UV light, specific chemicals, or heat.

What’s the matter with bioinks?

Formulating the right bioink is difficult. To ensure correct functionality, an ideal bioink should possess the mechanical, rheological (flow/deformation), and biological properties of the target tissues.

While significant strides have been made in the field of bioprinting in the last decade, the commercial availability and clinical application of bioprinting has been limited by the lack of appropriate bioinks.

What’s the status quo?

In a recent paper published in the International Society of Biofabrication, Machine learning-based design strategy for 3D-printable bioink: elastic modulus and yield stress determine printability, researchers prepared bioinks, measured their rheological properties, printed cell-laden constructs, and built a machine learning to predict printability by ink composition. Their bioinks were formulated from collagen, fibrin, and hyaluronic acid. A rheometer was used to measure stress-strain relationships and understand the flow/deformation properties of the bioinks. All constructs were observed under a scanning electron microscope at various magnifications. Using extrusion-based bioprinting, it was possible to measure printability as layers of bioink were deposited. When human dermal fibroblasts were added to the bioprinted structures, a cellular viability test was conducted to evaluate the bioink’s biocompatibility and ability to support cell growth. ImageJ, an image processing program, was used to assess the shape fidelity of the printed pattern.

Step 1: Formulating bioinks

To ensure a constant flow of oxygen and nutrients inside bioprinted tissues, vascular networks must be developed. And if we want to print vascular networks, a vascular bioink needs to provide a 3D environment that is conducive to cellular processes.

  • Elastin
  • Matrigel
  • Fibrin
  • Alginate
  • Chitosan
  • Agarose
  • Hyaluronic acid

Step 2: Bioprinting the tissues

Once we have developed a series of bioink formulations, it’s time to biofabricate multiple vascularized models and tissues for clinical transplantation. Each bioink formulation can be used to develop a vascularized tissue with distinct properties and processes.

Step 3: Determining their properties

Determining the individual factors that control the complex process of angiogenesis is very challenging. We’re interested in properties, such as tubulogenesis (tube formation) and cellular proliferation and migration, to analyze and compare angiogenesis in printed tissues.

  1. Adjustable gelation and stabilization to aid the bioprinting of structures with high shape fidelity;
  2. Biocompatibility and biodegradability to avoid a toxic or immunological response and to mimic the natural microenvironment of the tissue;
  3. Suitability for chemical modifications to meet tissue-specific needs; and
  4. The ability for large-scale production with minimal batch-to-batch variation.

Step 4: Training a ML model

Using an analytical model such as a decision tree classifier, we can analyze angiogenesis in our printed constructs. Thanks to the quantitative data we collected in the previous step, our decision trees can analyze the impact of biomaterials and printing processes on the biological performance of our bioink. As ML models do best, we can then identify patterns in the data to determine bioinks that promote angiogenesis.

Next steps…

Invented in 2003, bioprinting is still in its infancy. Currently, bioprinting can be used to print tissue models to research drugs and pills.

Acknowledgements

We would like to thank Prof. Darcy Wagner, Nicholas Karaiskos, Caner Dikyol, Maria Stang, Jaci Bliley, Emma Davoodi, Maxwell Nagarajan, Prof. Chee Kai Chua, Andrew Hudson, Erica Comber, and Ankita Gupta for meeting with us and for providing helpful advice and feedback.

--

--

Get the Medium app

A button that says 'Download on the App Store', and if clicked it will lead you to the iOS App store
A button that says 'Get it on, Google Play', and if clicked it will lead you to the Google Play store