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Digital biomanufacturing supporting vascularization in 3D bioprinting

viding any product application-specific quality, regu- to be employed in an in vitro assay. On the other hand,
latory or functional requirements. a printed construct that will be matured by a process
including immediate removal/exchange of the printed
2.5 Printing Technology support matrix post-printing may not require much
Many technologies supporting digital biomanufac- attention to a minor cytotoxicity in the ink. The means
turing are in use today. Chief among them for 3DBP of polymerizing the matrix monomer can be signifi-
are the laser-assisted, ink-jet, and extrusion (or mi- cant. These ranges from temperature; to UV, blue or
[8]
cro-extrusion) approaches . However, there are oth- green light; to chemical activators and their effect
er, very creative approaches being explored such as must be thoroughly examined.
magnetic-based techniques [18] . While there are many
overall similarities with these processes, there are Table 1. Lists of common bioink and 3DBP culture media
[7,19,20]
some very distinct chemical or mechanical require- component ingredients
ments to the bioinks for each. One distinction can be Structural matrix elements Cell culture elements
in required physico-mechanical characteristics of the Agarose Animal sera
solution — such as its surface tension, conductivity, Alginate Sera fractions
viscosity, flow characteristics, and any non-Newton- Carrageenan Hydrolysates
ian behavior. Other distinctions pertain to the biolo- Cellulose Cell and tissue extracts
gicals, such as consequences of the technique-spec- Chitosan Amino acids, nucleotides
ific printing pressures, shear or fluid volumes, requ- Collagen (poly) peptides
ired cell concentrations, and biocompatibility. A bio- Chondroitin Sulfate Defined proteins
ink must support both the mechanical and biological Decellularized ECM 1 Non-protein nitrogens
requirements of the printing approach adopted. Dextran Sugars, carbohydrates
Elastin Sterol and acyl lipids
2.6 Matrix, Scaffold or ECM
Fibrin A, B, C, and E Vitamins
Beyond the rheological requirements for the ink in the Gelatin Enzyme activities
printing process itself, the post-printing structural Gellan Gum Metals (trace elements)
characteristics of the bioink are an important aspect of HAMA Cytokines, factors
2
3DBP. As can be seen from Table 1, many HMW nat- Matrigel Peptide hormones
ural and synthetic polymers are employed in 3DBP. Methacrylated CS 3 Steroid hormones
Each has unique physical, chemical, and biological Methylcellulose Transport agents
properties. Furthermore, the means of controlling their PPF Detoxifying agents
4
state or and stiffness can have effects on other charac- PHEM Antiapoptotics
5
teristics of the bioink. The first criteria for such thick- PEGDA Protease inhibitors
6
ening agents or structural elements are that they be PEG / PEO Shear-force reducers
7
“biocompatible”. However, this term has different PGLCS , PVA , Pluronics Antibiotics
9
8
connotations depending upon the application. Charac- PLA , PGLRA , PGLYA 12 Antimycotics
11
10
teristics included in various concepts of the term in- Polyacrylamide Acid/base/buffers
clude lack of immunoactivity, cellular toxicity, cell Polycaprolactone Antibiotics
lineage differentiation activity, apoptosis induction, Silk fibroin Shear protectants
up-or down gene regulation/induction and more. Thr- HMW structures of above Viscosity enhancers
ough the application of cross-linking reagents, light, 1. ECM: Extra cellular matrix
heat or modulation of supramolecular chemistry, ac- 2. HAMA: Hyaluronic acid methacrylate
tive aspects of a bioink — the viscosity, strength, 3. CS: Chondroitin Sulfate
stiffness, visco-elastic plastic, surface and other cha- 4. PPF: Polypropylene fumarate
racteristics imparted by many matrix components — 5. PHEM: Polyhydroxyethylmethacrylate
6. PEGDA: Polyethylene glycol diacrylate
can be varied. Just what is included in the concept 7. PEG/PEO: Polyethylene glycol/oxide
of biocompatibility depends a lot upon the type of 8. PGLCS: Polyglycerol sebacate
cells employed and the final application of the con- 9. PVA: Polyvinyl alcohol
struct. Neither innate nor adaptive immune system 10. PLA: Polylactic acid
11. PGLRA: Polyglycerolic acid
activity may be very important in a printed construct 12. PGLYA: Polyglycolic acid
20 International Journal of Bioprinting (2017)–Volume 3, Issue 1