Bioprinting and Additive Manufacturing

Bioprinting

• Advances technical setups into biological applications

Additive Manufacturing and its Terms

• Additive Manufacturing, 3D printing, and Bioprinting are different terms for the same technology.

Additive Manufacturing Process

• Starts with a virtual model, which is then sliced, and finally results in a printed model.

AM/3D Printing Technologies

• Fused Filament Fabrication (FFF) also known as Fused Deposition Modeling (FDM).
• Stereolithography (SLA), utilizes Vat Polymerization.
• Direct Light Processing (DLP), utilizes Vat Polymerization.
• Selective Laser Sintering (SLS), uses Polymers.
• Direct Metal Laser Sintering (DMLS).
• Selective Laser Melting (SLM).
• Material Jetting.
• Binder Jetting.
• Electron Beam Melting (EBM).
• Drop on Demand (DOD).

Fused Deposition Modeling (FDM)

• A thermo-plastic filament is pushed through a heating chamber and extruded through a small nozzle.
• Material used includes thermoplastic filaments such as PLA, ABS, HIPS, TPU, TPE, PETG, and Nylon, including reinforced/charged materials.
• Curing process involves a temperature gradient.
• Relatively inexpensive with generally low accuracy and speed compared to other methods.

Stereolithography (SLA)

• Utilizes a container of liquid photopolymer resin, which hardens using UV light.
• Material is photo-polymeric resins which are hardened by UV light.
• Uses UV laser for curing.
• Typically is an expensive process, but has high accuracy.

Material Jetting

• Printing material is dropped through small diameter nozzles, similar to inkjet paper printing.
• Material used is photo-polymeric resins hardened by UV light.
• Uses UV light for curing.
• Can use multiple materials for parts and colors with high accuracy.

Binder Jetting

• Powder is spread in equal layers and binder is applied through jet nozzles to "glue" the particles together.
• Material is binder powder.
• Binder is used for curing.
• Parts can be made with different colours.

Key Idea

• Additive Manufacturing, 3D printing, and Bioprinting technologies each have particular features, aims, and issues, all sharing a common key idea.

Workflow

• A 3D file is produced, followed by the creation of an STL file, then printing, removal of prints, and finally post-processing.

3D@UniPV

• List of printers available at the University of Pavia: http://www-4.unipv.it/3d/
• Printers available:
  • Many 3NTR and leapfrog style printers
  • Renisha w AM 400
  • Cellink Inkredible

3D4MED

• 3D4MED website: https://www.3d4med.eu

Bioprinting

• Advances functionalizing 3D printed objects.

Tissue Engineering

• Interdisciplinary field applying engineering and life sciences to develop biological substitutes to restore, maintain, or improve biological tissue function or a whole organ.

Classic Paradigm in Tissue Engineering

• The classic paradigm involves scaffolds, cells, and growth factors

Scaffolds

• 3D and porous to mimic host tissue with mechanical properties, promote cell activities, and provide cells with a suitable and ECM-like environment.
• Conventional fabrication techniques include solvent casting, particulate leaching, gas foaming, phase separation, and freeze-drying.
• Additive manufacturing techniques include 3D printing, light-based techniques, extrusion-based techniques, and electrospinning.

Biofabrication

• Generation of biologically functional products with structural organization from living cells, micro-tissues, or hybrid tissue constructs, bioactive molecules or biomaterials either through top-down (Bioprinting) or bottom-up (Bioassembly) strategies, and subsequent tissue maturation processes.

BioP: Key Elements

• BioP, or bioprinting, consists of bio-ink and a bio-plotter.

Bioink vs Biomaterial Ink

• Bioink uses cells as a mandatory component, with optional materials, for processing with a biofabrication technique.
• Biomaterial ink uses additive manufacturing of biomaterials as inks for seeding of the scaffolds with cells.

BioP: Bio-ink Components

• Bio-ink comprises of biological components and a hydrogel.
• Biological components can include cells such as ESCs, MSCs, and iPSCs, as well as additives such as Growth Factors, Chemicals, Microcarriers and Drugs.
• Hydrogels can be natural or synthetic.
• Natural hydrogels: Alginate, Agarose, Collagen, Hyaluronic acid, Fibrin, Cellulose, Extracellular matrix.
• Synthetic hydrogels: Pluronic, Poly(ethyleneglycol), Polycaprolactone.
• Hydrogels use crosslinking.

Hydrogel Crosslinking

• Polymer + Crosslinker = Hydrogel
• Crosslinking can be ionic or covalent, photo crosslinking, or thermic.

Bio-ink features for 3D BioP

• Include printability, biocompatibility, degradation kinetics and byproducts, viscoelastic properties, mechanical properties, crosslinking/structure, permeability of oxygen and nutrients.
• Bio-ink requires a multidisciplinary approach.