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. Author manuscript; available in PMC: 2020 Oct 16.
Published in final edited form as: Adv Mater. 2020 Feb 11;32(12):e1906423. doi: 10.1002/adma.201906423

Table 1.

Overview of popular natural and synthetic components used in bioinks for extrusion-based bioprinting sorted by the main component. The table summarizes strategies for enabling the printability of common biomaterials using various functionalities and crosslinking approaches.

Natural Characteristics/chemical structure Functionalities/derivates Crosslinking/fabrication approaches Remarks/biological activity
Polypeptides
Gelatin Denaturated collagen
Mainly collagen I
Gly-Pro-X (most abundant)
Type A (derived from acidic-treated gelatin) → positive-charge at neutral pH
Type B (derived from alkali-treated gelatin)
→ negative-charge at neutral pH
Thermoreversible gelation
Without functionalization[3537] Blending with stabilizing component (e.g., alginate, fibrin[37])
Enzymatic crosslinking:
transglutaminase[38]
tyrosinase[39]
Radical (photo-) polymerization
Biodegradable
Cell adhesion motifs are present
Moderate biological activity if used alone
Common sources:
Bovine skin
Porcine skin
Fish skin
Methacrylated[23,40-44]
Allylated[45]
Norbornenet[46]
Thiolatedt[47,48]
Tyraminet[49] Furfury[50]
Radical (photo-) polymerization
Collagen type I Most abundant collagen in human body
Gly-Pro-X pH-dependent fibrillogenesis and gelation
Without functionalization pH-dependent crosslinking[5153] photo-crosslinking (e.g., with ribofavin[54]) crosslinked with genipin[55] Biodegradable
Cell adhesion motifs are present
Common sources:
Rat tail
Bovine skin
Rabbit skin
Calf skin
Fibrinogen/fibrin Fibrous and nonglobular glycoprotein
Thrombin (factor IIa) and factor
XIIIa can be used to covalently crosslink fibrinogen
Without functionalization[18,3537,43,51] Enzymatic crosslinking (factor IIa, XIIIa and IV) Additionally blended with stabilizing component (e.g., gelatin, hyaluronic acid, and Pluronic F127[37]) Biodegradable
Cell adhesion motifs are present
Limited long-term stability (can be prolonged by addition of aprotinin to culture medium)
Common sources:
Human plasma
Bovine plasma
Rat plasma
Silk/fibroin Silkworm cocoons Gly-Ser-Gly-Ala-Gly-Ala units[56] Recombinant spider protein GSSAAAAAAAASGPGGYGPE NQGPSGPGGYGPGGP Physical crosslinking by β-sheet crystal formation Without functionalization Physical crosslinking[57]
Blended with stabilizing component (e.g., gelatin[57]) Enzymatic crosslinking by tyrosinase[39]
Biodegradable Poor cell adhesion due to hydrophobic character[58]
Common sources: B. mori silkworm Recombinant silk protein eADF4(C16) mimicking Araneus diadematus silk protein sequences[59]
Poly-saccharides
Agarose d-Galactose and 3,6-anhydro-l-galactopyranose Thermoreversible gelation Without functionalization[60,61] Physical crosslinking Biologically inert
Biodegradable
Often used as sacrifcial material[12]
Can be used to modulate the viscosity[60]
Common sources: Red algae
Alginate Varying sequences and blocks of β-d-mannuronate (M) and α-l-guluronate (G)
Ionic gelation by divalent cations (e.g., Ca[2+])
Without functionalization Physical crosslinking via divalent ions
Often blended with, e.g., GelMA, nanocellulose or agarose[40,44,60,62]
to improve properties
Biologically inert
Sulfate can bind growth factors, such as FGF, TGF, and HFG
Common sources:
Brown algae
Sulfated[63]
Methacrylated[64]
Radical (photo-) polymerization
Characteristics/chemical structure Functionalities/derivates Crosslinking/fabrication approaches Remarks/biological activity
Hyaluronic acid Glycosaminoglycan (GAG) Units of d-glucuronic acid and N-acetyl-d-glucosamine Forms weak entangled molecular network[65] Without functionalization[37,66] Needs modifcation or blending with stabilizing component Biodegradable
Cell adhesion motifs are present
Can be used to modulate the viscosity
Common sources:
Bacteria
Bovine vitreous humor
Rooster comb
Methacrylated[41,6769]
Phenolic hydroxyl[49]
Thiolated[47,48]
Radical (photo-) polymerization
Poly(N-isopropylacrylamide)[67]
Adamantane (guest)[68]
β-Cyclodextrin (host)
Cucurbituril (host)[70]
1,6-diaminohexane (guest)
Lower critical solution temperature behavior (LCST)
Guest–host supramolecular assembly
Gellan gum Tetrasaccharide of repeating units of β-d-glucose, one β-d-glucuronic acid and one α-l-rhamnose[71]
Ionic gelation by mainly divalent cations Thermoreversible gelation
Without functionalization Physically crosslinked by cations Blended with stabilizing component (e.g., GelMA[42,72]) Biodegradable
Can be used to modulate the viscosity
Common sources:
Bacteria
Nano-cellulose Linear linked d-glucose units Cellulose nanocrystals (CNC) Cellulose nanofibers (CNF) Bacterial nanocellulose (BNC) Without functionalization Blended with stabilizing and/or bioactive component (e.g., algi-nate[63,73,74]
or hyaluronic acid[62,75])
Biodegradable
Can be used to modulate the viscosity
Common sources:
Plants
Bacteria
Dextran Branched or linear poly-α-d-glucose Methacrylatedt[66] Radical (photo-) polymerization Biologically inert
Chitosan Progressively deacetylated chitins Linear and random dispersed β-(1-4)-linked d-glucosamine and N-acetyl-d-glucosamine Long gelation time and low mechanical properties[76] Without functionalization Blended with stabilizing components (e.g., agarose and alginate[60]) Biodegradable[77]
improves cell survival[60]
cell adhesion properties controlled by N-acetylation groups[78]
antibacterial ability[79]
Common sources:
Chitin shells of seafood (e.g., crabs, shrimps, and prawns)
Carboxymethylated[60]
(water soluble)
Chondroitin sulfate Sulfated glycosaminoglycan (GAG) units of N-acetylgalactosamine and glucuronic acid Methacrylatedt[67] Radical (photo-) polymerization Biodegradable Common sources: bovine trachea Shark cartilage
Carrageenan Kappa-carrageenan
Ionic gelation mainly by potassium ions iota-carrageenan ionic gelation mainly by calcium ions
Thermoreversible gelation
Without functionalization[80] Physically crosslinked by cations Blended with a secondary component for covalent polymer network[80]
or nanosilicates[81]
Kappa-carrageenan mostly used due to its resemblance to natural glycosaminoglycans (GAGs)[82]
Common sources: Red algae
Methacrylatedt[83] Radical (photo-) polymerization
Characteristics/chemical structure Functionalities/derivates Crosslinking/fabrication approaches Remarks/biological activity
ECM mixtures
Matrigel Solubilized basement membrane preparation
Mainly laminin (L-111) and collagen IV, but in total over 1851 unique proteins and over 14 060 unique peptides[84]
Temperature-dependent gelation at around RT-37 °C
Without functionalization Temperature-triggered gelation Biodegradable
Cell adhesion motifs are present
Highly bioactive due to growth factors and vast amount of proteins and peptides
No defned composition
Batch-to-batch variations
Common sources:
Engelbreth–Holm–Swarm mouse sarcoma
dECM Decellularized extracellular matrix of a specifc tissue like heart,[8587]
cartilage,[85]
adipose,[85,88,89]
aorta,[90]
skeletal muscle,[91]
and liver[92]
Temperature-dependent gelation
Without functionalization Temperature-triggered gelation Blended with stabilizing component (e.g., thiolated gelatin, hyaluronic acid, and PEGDA[29]) Vitamin B2-induced UV-A crosslinking[86] Biodegradable
Cell adhesion motifs are present
Biodegradable
Highly bioactive
No defned composition
Batch-to-batch variations
Common sources: mammalian tissue
Synthetic
PEG Poly(ethylene glycol) H(OCH2CH2)nOH Linear or branched Diacrylatedt[18]
Tetra-acrylatedt[44,48]
Radical (photo-) polymerization Biologically inert
Methacrylated[61]
Fibrinogen and diacrylate functionalization[18]
Succinimidyl valeratet[43] Amin-carboxylic acid coupling (NHS ester reaction) with, e.g., proteins
Pluronic Triblock copolymer of poly(ethylene oxide)
Nonionic tenside
Without functionalization[37] Temperature-triggered gelation Biologically inert
Often used as sacrifcial material[37]
Not suitable for long-term cell culture
Diacrylated[93] Radical (photo-) polymerization
Additives
Nanosilicates Laponite
Na[+] 07[(Mg5.5Li0.3)Si8O20(OH)4]-0.7)
Without functionalization[83,94] Physically crosslinked Blended with other bioink components (e.g., kappa-carrageenan and GelMA[95] Used to modulate the viscosity of an ink to improve printability Can improve cell adhesion and response[9698]
Glycerol C3H8O3
Viscous and hygroscopic liquid Backbone of many lipids
Without functionalization Blended with other bioink components Can help to induce crosslinking of silk[57]
Can prevent nozzle clogging and used as rheology modifer[37]