Collagen as Bioink for Bioprinting: A Comprehensive Review

Egor Olegovich Osidak, Vadim Igorevich Kozhukhov, Mariya Sergeevna Osidak, Sergey Petrovich Domogatskiy

Article ID: 270
Vol 6, Issue 3, 2020, Article identifier:270

VIEWS - 670 (Abstract) 171 (PDF)


Biomaterials made using collagen are successfully used as a three-dimensional (3D) substrate for cell culture and considered to be promising scaffolds for creating artificial tissues. An important task that arises for engineering such materials is the simulation of physical and morphological properties of tissues, which must be restored or replaced. Modern additive technologies, including 3D bioprinting, can be applied to successfully solve this task. This review provides the latest evidence on advances of 3D bioprinting with collagen in the field of tissue engineering. It contains modern approaches for printing pure collagen bioinks consisting only of collagen and cells, as well as the obtained results from the use of pure collagen bioinks in different fields of tissue engineering.


Collagen, Three-dimensional bioprinting, Tissue engineering, Cell-laden hydrogels

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Xia Z, Jin S, Ye K, 2018, Tissue and organ 3D bioprinting. SLAS Technol, 23:301–314. DOI: 10.1177/2472630318760515.

Nagarajan N, Dupret-Bories A, Karabulut E, et al., 2018, Enabling personalized implant and controllable biosystem development through 3D printing. Biotechnol Adv, 36:52533. DOI: 10.1016/j.biotechadv.2018.02.004.

Hospodiuk M, Dey M, Sosnoski D, et al., 2017, The bioink: A comprehensive review on bioprintable materials. Biotechnol Adv, 35:217-239. DOI: 10.1016/j.biotechadv.2016.12.006.

Kloxin AM, Kloxin CJ, Bowman CN, et al., 2010, Mechanical properties of cellularly responsive hydrogels and their experimental determination. Adv Mater, 22:3484–94. DOI: 10.1002/adma.200904179.

Antoine EE, Vlachos PP, Rylander MN, 2014, Review of collagen I hydrogels for bioengineered tissue microenvironments: Characterization of mechanics, structure, and transport. Tissue Eng Part B Rev, 20:683–96. DOI: 10.1089/ten.teb.2014.0086.

Lynn AK, Yannas IV, Bonfield W, 2004, Antigenicity and immunogenicity of collagen. J Biomed Mater Res B App Biomater, 71:343–54. DOI: 10.1002/jbm.b.30096.

Parenteau-Bareil R, Gauvin R, Berthod F, 2010, Collagen based biomaterials for tissue engineering applications. Materials (Basel), 3:1863–87. DOI: 10.3390/ma3031863.

Sriya Y, Shibu C, Ashis KB, et al., 2019, Tissue-Specific Bioink from Xenogeneic Sources for 3D Bioprinting of Tissue Constructs, in Xenotransplantation-comprehensive Study, Shuji Miyagawa, Intech Open, Available from: https://www. DOI: 10.5772/intechopen.89695.

Gelse K, Pöschl E, Aigner T, 2003, Collagens--structure, function, and biosynthesis. Adv Drug Deliv Rev, 55:1531–46. DOI: 10.1016/j.addr.2003.08.002.

Ricard-Blum S, 2011, The collagen family. Cold Spring Harb Perspect Biol, 3:a004978. DOI: 10.1101/cshperspect.a004978.

Włodarczyk-Biegun MK, Del Campo A, 2017, 3D bioprinting of structural proteins. Biomaterials, 134:180–201. DOI: 10.1016/j.biomaterials.2017.04.019.

Yoon H, Lee JS, Yim H, et al., 2016, Development of cell laden 3D scaffolds for efficient engineered skin substitutes by collagen gelation. RSC Adv, 6:21439–47. DOI: 10.1039/c5ra19532b.

Hinton TJ, Jallerat Q, Palchesko RN, et al., 2015, Three-dimensional printing of complex biological structures by freeform reversible embedding of suspended hydrogels. Sci Adv, 1:e1500758. DOI: 10.1126/sciadv.1500758.

Maxson EL, Young MD, Noble C, et al., 2019, In vivo remodeling of a 3D-bioprinted tissue engineered heart valve scaffold. Bioprinting, 16:e00059. DOI: 10.1016/j.bprint.2019. e00059.

Lee A, Hudson AR, Shiwarski DJ, et al., 2019, 3D bioprinting of collagen to rebuild components of the human heart. Science, 365:482–87. DOI: 10.1126/science.aav9051.

Diamantides N, Wang L, Pruiksma T, et al., 2017, Correlating rheological properties and printability of collagen bioinks: The effects of riboflavin photocrosslinking and pH. Biofabrication, 9:034102. DOI: 10.1088/1758-5090/aa780f.

Osidak EO, Karalkin PA, Osidak MS, et al., 2019, Viscoll collagen solution as a novel bioink for direct 3D bioprinting. J Mater Sci Mater Med, 30:31. DOI: 10.1007/s10856-019-6233-y.

Lian D, Jiheng L, Conghu L, et al., 2013, Effects of NaCl on the rheological behavior of collagen solution, Korea-Aust Rheol J, 25:137–144. DOI: 10.1007/s13367-013-0014-9.

Lai G, Li Y, Li G, 2008, Effect of concentration and temperature on the rheological behavior of collagen solution. Int J Biol Macromol, 42:285–91.

Rhee S, Putzer JL, Mason BN, et al., 2016, 3D Bioprinting of spatially heterogeneous collagen constructs for cartilage tissue engineering. ACS Biomater Sci Eng, 2:1800–1805. DOI: 10.1021/acsbiomaterials.6b00288.

Lee H, Yang GH, Kim M, et al., 2018, Fabrication of micro/nanoporous collagen/dECM/silk-fibroin biocomposite scaffolds using a low temperature 3D printing process for bone tissue regeneration. Mater Sci Eng C Mater Biol Appl,84:140-147. DOI: 10.1016/j.msec.2017.11.013.

Moncal KK, Ozbolat V, Datta P, et al., 2019, Thermally controlled extrusion-based bioprinting of collagen. J MaterSci: Mater Med, 30:55. DOI: 10.1007/s10856-019-6258-2.

Koch L, Deiwick A, Schlie S, et al., 2012, Skin tissue generation by laser cell printing. Biotechnol Bioeng,109:1855–63.

Michael S, Sorg H, Peck CT, et al., 2013, Tissue engineered skin substitutes created by laser-assisted bioprinting form skin-like structures in the dorsal skin fold chamber in mice. PLoS One, 8:e57741. DOI: 10.1371/journal.pone.0057741.

Shi Y, Xing TL, Zhang HB, et al., 2018, Tyrosinase-doped bioink for 3D bioprinting of living skin constructs. Biomed Mater, 13:035008. DOI: 10.1088/1748-605x/aaa5b6.

Skardal A, Mack D, Kapetanovic E, et al., 2012, Bioprinted amniotic fluid-derived stem cells accelerate healing of large skin wounds. Stem Cells Transl Med, 11:792–802. DOI:10.5966/sctm.2012-0088.

Albanna M, Binder KW, Murphy SV, et al., 2019, In Situ bioprinting of autologous skin cells accelerates wound healing of extensive excisional full-thickness wounds. Sci Rep, 9:1856. DOI: 10.1038/s41598-018-38366-w.

Kim W, Kim G, 2019, Collagen/bioceramic-based composite bioink to fabricate a porous 3D hASCs-laden structure for bone tissue regeneration. Biofabrication, 12:015007. DOI: 10.1088/1758-5090/ab436d.

Kim WJ, Yun HS, Kim GH, 2017, An innovative cell-laden α-TCP/collagen scaffold fabricated using a two-step printing process for potential application in regenerating hard tissues. Sci Rep, 7:3181. DOI: 10.1038/s41598-017-03455-9.

Lin KF, He S, Song Y, et al., 2016, Low-temperature additive manufacturing of biomimic three-dimensional hydroxyapatite/collagen scaffolds for bone regeneration. ACS Appl Mater Interfaces, 8:6905–16.

Marques CF, Diogo GS, Pina S, et al., 2019, Collagen based bioinks for hard tissue engineering applications: A comprehensive review. J Mater Sci Mater Med, 30:32. DOI: 10.1007/s10856-019-6234-x.

Mishra R, Basu B, Kumar A, 2019, Physical and cytocompatibility properties of bioactive glass-polyvinyl alcohol-sodium alginate biocomposite foams prepared via solgel processing for trabecular bone regeneration. J Mater Sci: Mater Med, 20:2493–500. DOI: 10.1007/s10856-009-3814-1.

Shim JH, Jang KM, Hahn SK, et al., 2016, Three-dimensional bioprinting of multilayered constructs containing human mesenchymal stromal cells for osteochondral tissue regeneration in the rabbit knee joint. Biofabrication, 8:014102. DOI: 10.1088/1758-5090/8/1/014102.

Yang X, Lu Z, Wu H, et al., 2018, Collagen-alginate as bioink for three-dimensional (3D) cell printing based cartilage tissue engineering. Mater Sci Eng C Mater Biol Appl, 83:195–201. DOI: 10.1016/j.msec.2017.09.002.

Cui H, Miao S, Esworthy T, et al, 2018, 3D bioprinting for cardiovascular regeneration and pharmacology. Adv Drug Del Rev, 132:252–269.

Lewis PL, Shah RN, 2016, 3D Printing for liver tissue engineering: Current approaches and future challenges. Curr Transpl Rep, 3:100–108. DOI: 10.1007/s40472-016-0084-y.

Shim JH, Kim JY, Park M, et al., 2011, Development of a hybrid scaffold with synthetic biomaterials and hydrogel using solid freeform fabrication technology. Biofabrication, 3:034102. DOI: 10.1088/1758-5082/3/3/034102.

Mazzocchi A, Devarasetty M, Huntwork R, et al., 2018, Optimization of collagen Type I-hyaluronan hybrid bioink for 3D bioprinted liver microenvironments. Biofabrication, 11:015003. DOI: 10.1088/1758-5090/aae543.

Klein S, Vykoukal J, Felthaus O, et al., 2016, Collagen Type I conduits for the regeneration of nerve defects. Materials (Basel), 9:219. DOI: 10.3390/ma9040219.

Madduri S, Feldman K, Tervoort T, et al., 2010, Collagen nerve conduits releasing the neurotrophic factors GDNF and NGF. J Control Release, 143:168-74. DOI: 10.1016/j.jconrel.2009.12.017.

O’Connor SM, Stenger DA, Shaffer KM, et al., 2000, Primary neural precursor cell expansion, differentiation and cytosolic Ca(2+) response in three-dimensional collagen gel. J Neurosci Methods, 102:187–95. DOI: 10.1016/s0165-0270(00)00303-4.

Labour MN, Vigier S, Lerner D, et al., 2016, 3D compartmented model to study the neurite-related toxicity of Aβ aggregates included in collagen gels of adaptable porosity. Acta Biomater, 37:38–49. DOI: 10.1016/j.actbio.2016.04.001.

Lee W, Pinckney J, Lee V, et al., 2009, Three-dimensional bioprinting of rat embryonic neural cells. Neuroreport, 20:798–803.

Lee YB, Polio S, Lee W, et al., 2010, Bio-printing of collagen and VEGF-releasing fibrin gel scaffolds for neural stem cell culture. Exp Neurol, 223:645–52. DOI: 10.1016/j.expneurol.2010.02.014.

Chen C, Zhao ML, Zhang RK, et al., 2017, Collagen/heparin sulfate scaffolds fabricated by a 3D bioprinter improved mechanical properties and neurological function after spinal cord injury in rats. J Biomed Mater Res A, 105:1324–32.DOI: 10.1002/jbm.a.36011.

Zhang B, Xue Q, Li J, et al., 2019, 3D bioprinting for artificial cornea: Challenges and perspectives. Med Eng Phys, 71:68–78.

Isaacson A, Swioklo S, Connon CJ, 2018, 3D bioprinting of a corneal stroma equivalent. Exp Eye Res, 173:188–193. DOI: 10.1016/j.exer.2018.05.010.

Campos DD, Rohde M, Ross M, et al., 2019, Corneal bioprinting utilizing collagen‐based bioinks and primary human keratocytes. J Biomed Mater Res Part A, 107:1945–53. DOI:10.1002/jbm.a.36702.



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