Abstract
The goal of scaffold-based tissue engineering is to create synthetic replacements for natural tissues. Since tissues are comprised of composite structures, it is challenging for a single biomaterial to appropriately mimic the cellular and extracellular natural environment. To incorporate multiple biomaterials into multiphasic scaffolds, additive manufacturing (3D printing) technologies have arisen as a universal scaffold fabrication platform. However, combining multiple printed biomaterials is technically difficult since many printing processes rely on fundamentally different operating principles. Furthermore, commercial equipment is often cost prohibitive, and there remains limited open-source alternatives. To address the lack of equipment, systematic engineering design was applied to build an open-source 3D bioprinter capable of printing with multiple materials using multiple technologies. The design requirements were identified through a user-centred design process with the overarching aim of being a multi-material, multi-technology system while adhering to engineering standards (AS IEC 61010). The system was constructed to be open source, and detailed diagrams, parts lists, computer-aided design (CAD) models, standard operating procedures (SOP’s) and cost breakdowns on each subsystem are provided. To validate and test the design, 4 popular extrusion and electrohydrodynamic printing processes were tested: inks, solution electrospinning, melt electrospinning and melt extrusion. To demonstrate the utility of the Biofabricator for creating multi-material, multi-technology scaffolds, 4 multiphasic scaffolds were designed and presented as case studies. The open-source Biofabricator is an advanced bioprinting platform capable of fabricating multi-material, multi-technology scaffolds to support cutting-edge future research in tissue engineering.
Similar content being viewed by others
Data availability
The engineering drawings and bill of materials are available online at github.com/MatthewLanaro/Biofabricator.
References
Hollister SJ (2005) Porous scaffold design for tissue engineering. Nat Mater 4(7):518–524. https://doi.org/10.1038/nmat1421
Goins A, Webb AR, Allen JB (2019) Multi-layer approaches to scaffold-based small diameter vessel engineering: a review. Mater Sci Eng C 97:896–912. https://doi.org/10.1016/J.MSEC.2018.12.067
Izadifar Z, Chen X, Kulyk W (2012) Strategic design and fabrication of engineered scaffolds for articular cartilage repair. J Funct Biomater 3(4):799–838. https://doi.org/10.3390/jfb3040799
Li JJ, Kaplan DL, Zreiqat H (2014) Scaffold-based regeneration of skeletal tissues to meet clinical challenges. J Mater Chem B 2(42):7272–7306. https://doi.org/10.1039/c4tb01073f
Chaudhari A et al (2016) Future prospects for scaffolding methods and ciomaterials in skin tissue engineering: a review. Int J Mol Sci 17(12):1974. https://doi.org/10.3390/ijms17121974
Do A-V, Khorsand B, Geary SM, Salem AK (2015) 3D printing of scaffolds for tissue regeneration applications. Adv Healthc Mater 4(12):1742–1762. https://doi.org/10.1002/adhm.201500168
Grémare A, Guduric V, Bareille R, Heroguez V, Latour S, L'heureux N, Fricain JC, Catros S, le Nihouannen D (2018) Characterization of printed PLA scaffolds for bone tissue engineering. J. Biomed. Mater. Res. - Part A 106(4):887–894. https://doi.org/10.1002/jbm.a.36289
Posa F, di Benedetto A, Ravagnan G, Cavalcanti-Adam EA, Lo Muzio L, Percoco G, Mori G (2020) Bioengineering bone tissue with 3d printed scaffolds in the presence of oligostilbenes. Materials (Basel) 13(20):1–12. https://doi.org/10.3390/ma13204471
Nair LS, Laurencin CT (Aug. 2007) Biodegradable polymers as biomaterials. Prog Polym Sci 32(8–9):762–798. https://doi.org/10.1016/J.PROGPOLYMSCI.2007.05.017
Hospodiuk M, Dey M, Sosnoski D, Ozbolat IT (Mar. 2017) The bioink: a comprehensive review on bioprintable materials. Biotechnol Adv 35(2):217–239. https://doi.org/10.1016/J.BIOTECHADV.2016.12.006
Stanton MM, Samitier J, Sánchez S (Jul. 2015) Bioprinting of 3D hydrogels. Lab Chip 15(15):3111–3115. https://doi.org/10.1039/C5LC90069G
Jafari M, Paknejad Z, Rad MR, Motamedian SR, Eghbal MJ, Nadjmi N, Khojasteh A (2017) Polymeric scaffolds in tissue engineering: a literature review. J Biomed Mater Res Part B Appl Biomater 105(2):431–459. https://doi.org/10.1002/jbm.b.33547
Lee SJ, Lee JH, Park J, Kim WD, Park SA (2020) Fabrication of 3D printing scaffold with porcine skin decellularized bio-ink for soft tissue engineering. Materials (Basel). 13(16):1–9. https://doi.org/10.3390/MA13163522
Lanaro M, Booth L, Powell SK, Woodruff MA (2018) Electrofluidodynamic technologies for biomaterials and medical devices: melt electrospinning. In: Guarino V, Ambrosio L (eds) Electrofluidodynamic Technologies (EFDTs) for Biomaterials and Medical Devices. Woodhead Publishing, pp 37–69
G. Mitchell and Royal Society of Chemistry (Great Britain), Electrospinning : principles, practice and possibilities.
Bock N, Dargaville TR, Woodruff MA (2012) Electrospraying of polymers with therapeutic molecules: state of the art. Prog Polym Sci 37(11):1510–1551. https://doi.org/10.1016/J.PROGPOLYMSCI.2012.03.002
Skardal A, Devarasetty M, Kang HW, Mead I, Bishop C, Shupe T, Lee SJ, Jackson J, Yoo J, Soker S, Atala A (2015) A hydrogel bioink toolkit for mimicking native tissue biochemical and mechanical properties in bioprinted tissue constructs. Acta Biomater 25:24–34. https://doi.org/10.1016/J.ACTBIO.2015.07.030
Chimene D, Lennox KK, Kaunas RR, Gaharwar AK (2016) Advanced bioinks for 3D printing: a materials science perspective. Ann Biomed Eng 44(6):2090–2102. https://doi.org/10.1007/s10439-016-1638-y
Sengupta P, Surwase SS, Prasad BL (2018) Modification of porous polyethylene scaffolds for cell attachment and proliferation. Int J Nanomedicine 13(T-NANO 2014 Abstracts):87–90. https://doi.org/10.2147/IJN.S125000
Intranuovo F, Gristina R, Fracassi L, Lacitignola L, Crovace A, Favia P (2016) Plasma processing of scaffolds for tissue engineering and regenerative medicine. Plasma Chem Plasma Process 36(1):269–280. https://doi.org/10.1007/s11090-015-9667-0
Shah J, Snider B, Clarke T, Kozutsky S, Lacki M, Hosseini A (2019) Large-scale 3D printers for additive manufacturing: design considerations and challenges. Int J Adv Manuf Technol 104(9–12):3679–3693. https://doi.org/10.1007/s00170-019-04074-6
Ali MH, Mir-Nasiri N, Ko WL (2016) Multi-nozzle extrusion system for 3D printer and its control mechanism. Int J Adv Manuf Technol 86(1–4):999–1010. https://doi.org/10.1007/s00170-015-8205-9
“The Top 10 Bioprinters - 3D Printing Industry.”
Wiggermann N, Rempel K, Zerhusen RM, Pelo T, Mann N (2019) Human-centered design process for a hospital bed: promoting patient safety and ease of use. Ergon Des Q Hum Factors Appl 27(2):4–12. https://doi.org/10.1177/1064804618805570
Jurca G, Hellmann TD, Maurer F (2017) Agile user-centered design. In: The Wiley Handbook of Human Computer Interaction. John Wiley & Sons, Ltd, Chichester, UK, pp 109–123
Safety requirements for electrical equipment for measurement, control and laboratory use - Part 1: General requirements (IEC 61010–1:2001 MOD). Standards Australia, 2003
Lucassen G, Dalpiaz F, van der Werf JMEM, Brinkkemper S (2015) Forging high-quality user stories: towards a discipline for agile requirements. In: 2015 IEEE 23rd International Requirements Engineering Conference (RE), Aug, pp 126–135. https://doi.org/10.1109/RE.2015.7320415
Laplume A, Anzalone GC, Pearce JM (2016) Open-source, self-replicating 3-D printer factory for small-business manufacturing. Int J Adv Manuf Technol 85(1–4):633–642. https://doi.org/10.1007/s00170-015-7970-9
Wu C, Yi R, Liu YJ, He Y, Wang CCL (2016) Delta DLP 3D printing with large size. IEEE Int Conf Intell Robot Syst., vol. 2016-November:2155–2160. https://doi.org/10.1109/IROS.2016.7759338
Needs SH, Diep TT, Bull SP, Lindley-Decaire A, Ray P, Edwards AD (2019) Exploiting open source 3D printer architecture for laboratory robotics to automate high-throughput time-lapse imaging for analytical microbiology. PLoS One 14(11). https://doi.org/10.1371/journal.pone.0224878
Ramcharitar S, Serruys PW (2008) Fully biodegradable coronary stents. Am J Cardiovasc Drugs 8(5):305–314. https://doi.org/10.2165/00129784-200808050-00003
Berner A, Henkel J, Woodruff MA, Saifzadeh S, Kirby G, Zaiss S, Gohlke J, Reichert JC, Nerlich M, Schuetz MA, Hutmacher DW (2017) Scaffold–cell bone engineering in a validated preclinical animal model: precursors vs differentiated cell source. J Tissue Eng Regen Med 11(7):2081–2089. https://doi.org/10.1002/term.2104
Ito S, Steininger J, Schitter G (2015) Low-stiffness dual stage actuator for long rage positioning with nanometer resolution. Mechatronics 29:46–56. https://doi.org/10.1016/j.mechatronics.2015.05.007
Miller JE, Longstaff AP, Parkinson S, Fletcher S (2017) Improved machine tool linear axis calibration through continuous motion data capture. Precis Eng 47:249–260. https://doi.org/10.1016/j.precisioneng.2016.08.010
Mackay ME, Swain ZR, Banbury CR, Phan DD, Edwards DA (2017) The performance of the hot end in a plasticating 3D printer. J Rheol (N Y N Y) 61(2):229–236. https://doi.org/10.1122/1.4973852
Rabionet M et al (2017) Electrospinning PCL scaffolds manufacture for three-dimensional breast cancer cell culture. Polymers (Basel) 9(12):328. https://doi.org/10.3390/polym9080328
Dias J, Bártolo P (2013) Morphological characteristics of electrospun PCL meshes - the influence of solvent type and concentration. Procedia CIRP 5:216–221. https://doi.org/10.1016/j.procir.2013.01.043
Wu W, DeConinck A, Lewis JA (2011) Omnidirectional printing of 3D microvascular networks. Adv Mater 23(24):H178–H183. https://doi.org/10.1002/adma.201004625
Paxton N, Smolan W, Böck T, Melchels F, Groll J, Jungst T (2017) Proposal to assess printability of bioinks for extrusion-based bioprinting and evaluation of rheological properties governing bioprintability. Biofabrication 9(4):044107. https://doi.org/10.1088/1758-5090/aa8dd8
Heath DE, Lannutti JJ, Cooper SL (2010) Electrospun scaffold topography affects endothelial cell proliferation, metabolic activity, and morphology. J Biomed Mater Res - Part A 94(4):1195–1204. https://doi.org/10.1002/jbm.a.32802
Liao S, Theodoropoulos C, Blackwood KA, Woodruff MA, Gregory SD (2018) Melt electrospun bilayered scaffolds for tissue integration of a suture-less inflow cannula for rotary blood pumps. Artif Organs 42(5):E43–E54. https://doi.org/10.1111/aor.13018
Nam J, Huang Y, Agarwal S, Lannutti J (2007) Improved cellular infiltration in electrospun fiber via engineered porosity. Tissue Eng 13(9):2249–2257. https://doi.org/10.1089/ten.2006.0306
Blakeney B, Tambralli A, Anderson J, Andukuri A (2011) Cell infiltration and growth in a low density, uncompressed three-dimensional electrospun nanofibrous scaffold. Biomaterials
Wang K, Zhu M, Li T, Zheng W, Li L, Xu M, Zhao Q, Kong D, Wang L (2014) Improvement of cell infiltration in electrospun polycaprolactone scaffolds for the construction of vascular grafts. J Biomed Nanotechnol 10(8):1588–1598
Baker BM, Gee AO, Metter RB, Nathan AS, Marklein RA, Burdick JA, Mauck RL (2008) The potential to improve cell infiltration in composite fiber-aligned electrospun scaffolds by the selective removal of sacrificial fibers. Biomaterials 29(15):2348–2358. https://doi.org/10.1016/j.biomaterials.2008.01.032
Kim T, Kim C, Kim J, Jin S, Yoon S (2016) Three-dimensional culture and interaction of cancer cells and dendritic cells in an electrospun nano-submicron hybrid fibrous scaffold. Int J.
Yu C, Jiang J (2020) A perspective on using machine learning in 3D bioprinting. Int J Bioprinting 6(1):4–11. https://doi.org/10.18063/ijb.v6i1.253
Shi W, Sun M, Hu X, Ren B, Cheng J, Li C, Duan X, Fu X, Zhang J, Chen H, Ao Y (2017) Structurally and functionally optimized silk-fibroin–gelatin scaffold using 3D printing to repair cartilage injury in vitro and in vivo. Adv Mater 29(29):1–7. https://doi.org/10.1002/adma.201701089
Sun Y, You Y, Jiang W, Zhai Z, Dai K (2019) 3D-bioprinting a genetically inspired cartilage scaffold with GDF5-conjugated BMSC-laden hydrogel and polymer for cartilage repair. Theranostics 9(23):6949–6961. https://doi.org/10.7150/thno.38061
Laronda MM et al (2017) A bioprosthetic ovary created using 3D printed microporous scaffolds restores ovarian function in sterilized mice. Nat Commun. 8(May):1–10. https://doi.org/10.1038/ncomms15261
Gao M, Zhang H, Dong W, Bai J, Gao B, Xia D, Feng B, Chen M, He X, Yin M, Xu Z, Witman N, Fu W, Zheng J (2017) Tissue-engineered trachea from a 3D-printed scaffold enhances whole-segment tracheal repair. Sci Rep 7(1):1–12. https://doi.org/10.1038/s41598-017-05518-3
Reichert JC et al (2012) A tissue engineering solution for segmental defect regeneration in load-bearing long bones. Sci Transl Med. 4(141). https://doi.org/10.1126/scitranslmed.3003720
Tovar N, Witek L, Atria P, Sobieraj M, Bowers M, Lopez CD, Cronstein BN, Coelho PG (2018) Form and functional repair of long bone using 3D-printed bioactive scaffolds. J Tissue Eng Regen Med 12(9):1986–1999. https://doi.org/10.1002/term.2733
Castilho M, van Mil A, Maher M, Metz CHG, Hochleitner G, Groll J, Doevendans PA, Ito K, Sluijter JPG, Malda J (2018) Melt electrowriting allows tailored microstructural and mechanical design of scaffolds to advance functional human myocardial tissue formation. Adv Funct Mater 28(40):1–10. https://doi.org/10.1002/adfm.201803151
Hochleitner G, Chen F, Blum C, Dalton PD, Amsden B, Groll J (2018) Melt electrowriting below the critical translation speed to fabricate crimped elastomer scaffolds with non-linear extension behaviour mimicking that of ligaments and tendons. Acta Biomater 72:110–120. https://doi.org/10.1016/j.actbio.2018.03.023
Saidy NT, Wolf F, Bas O, Keijdener H, Hutmacher DW, Mela P, de-Juan-Pardo EM (2019) Biologically inspired scaffolds for heart valve tissue engineering via melt electrowriting. Small 15(24):1–15. https://doi.org/10.1002/smll.201900873
Hammerl A, Diaz Cano CE, De-Juan-Pardo EM, van Griensven M, Poh PSP (2019) A growth factor-free co-culture system of osteoblasts and peripheral blood mononuclear cells for the evaluation of the osteogenesis potential of melt-electrowritten polycaprolactone scaffolds. Int J Mol Sci. 20(5). https://doi.org/10.3390/ijms20051068
Díaz-Tena E, Rodríguez-Ezquerro A, Marcaide LNLDL, Bustinduy LG, Sáenz AE (2014) A sustainable process for material removal on pure copper by use of extremophile bacteria. J Clean Prod 84(1):752–760. https://doi.org/10.1016/j.jclepro.2014.01.061
Díaz-Tena E, Barona A, Gallastegui G, Rodríguez A, López de Lacalle LN, Elías A (2017) Biomachining: metal etching via microorganisms. Crit Rev Biotechnol 37(3):323–332. https://doi.org/10.3109/07388551.2016.1144046
Díaz-Tena E, Gallastegui G, Hipperdinger M, Donati ER, Ramírez M, Rodríguez A, López de Lacalle LN, Elías A (2016) New advances in copper biomachining by iron-oxidizing bacteria. Corros Sci 112:385–392. https://doi.org/10.1016/j.corsci.2016.08.001
Author information
Authors and Affiliations
Contributions
Contributors statement of contribution
Matthew Lanaro Provided design briefs and incorporated work done by Amelia Lu, Archibald Lightbody-Gee and David Hedger. Designed all other parts of the Biofabricator, wrote manuscript
Amelia Lu Design of frame
Archibald Lightbody-Gee Design of flat plate and rotating mandrel
David Hedger Initial design of printing head
Sean K. Powell Editing
David W. Holmes Providing advice on the construction of the Biofabricator, manuscript editing
Maria A. Woodruff Oversaw study and provided feedback on manuscript
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflicts of interest.
Ethical approval
n/a
Consent to participate
n/a
Consent to publish
Yes
Code availability
The firmware needed to run the control board is available at github.com/MatthewLanaro/Biofabricator.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
ESM 1
(DOCX 122 kb)
Rights and permissions
About this article
Cite this article
Lanaro, M., Luu, A., Lightbody-Gee, A. et al. Systematic design of an advanced open-source 3D bioprinter for extrusion and electrohydrodynamic-based processes. Int J Adv Manuf Technol 113, 2539–2554 (2021). https://doi.org/10.1007/s00170-021-06634-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00170-021-06634-1