AccScience Publishing / MSAM / Volume 1 / Issue 1 / DOI: 10.18063/msam.v1i1.7
ORIGINAL RESEARCH ARTICLE

From 3D printed molds to bioprinted scaffolds: A hybrid material extrusion and vat polymerization bioprinting approach for soft matter constructs 

Zainab N. Khan1† Hamed I. Albalawi1† Alexander U. Valle-Pérez1 Ali Aldoukhi1 Noofa Hammad1 Elena Herrera-Ponce de León1 Sherin Abdelrahman1 Charlotte A. E. Hauser1,2*
Show Less
1 Laboratory for Nanomedicine, Division of Biological and Environmental Science and Engineering, King Abdullah University for Science and Technology, Thuwal, 23955- 6900, Saudi Arabia
2 Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal 23955, Saudi Arabia
Accepted: 11 March 2022 | Published: 28 March 2022
© 2022 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Three-dimensional (3D) bioprinting methods vary in difficulty and complexity depending on the application desired and biomaterials used. 3D biofabrication is gaining increased traction with enhanced additive manufacturing technologies. Yet, high print resolution and efficiency for the fabrication of complex constructs still prove to be challenging. An intricate balance between biomaterial composition, machine maneuverability, and extrusion mechanism is required. While soft bioinks are highly desirable when used as a biodegradable scaffold material for tissue and organ fabrication, mechanical stiffness and shape fidelity are often compromised. Alternately, post-printing ultraviolet and chemical crosslinking processes improve fidelity but threaten cell viability. Herein, we propose a hybrid fabrication approach to facilitate 3D bioprinting using soft bioinks with instantaneous gelation properties while maintaining shape fidelity for tissue and organ structures of complex geometries. The approach entails a multi-step “3D Printed Molds to Scaffolds” method, which uses additive manufacturing to create accurate negative support structures for the desired construct. A tissue or organ model is first designed in computer-aided design (CAD) modeling software to create a negative mold structure of the desired tissue or organ. Using a Formlabs® SLA 3D printer, the negative mold is fabricated at desired scale using a biocompatible elastic resin. Then, a robotic 3D bioprinting system is loaded with a sliced g-code of the CAD model. The robot start position is aligned with the placement of the fabricated mold on the printbed. Microfluidic pumps deliver three solutions through a customized nozzle to extrude peptide bioink, which gels instantaneously. The initial layers of the structure are formed within the mold to create a solid foundation of the construct. The hybrid approach was found to enhance fidelity considerably and enabled the printing of a complex human ear structure. It is promising for tissue and organ fabrication as it offers a cost-effective support structure without increasing printing time. It could also be used as a rapid prototyping approach for researchers who do not have access to 3D bioprinting systems. Biofabrication, from printed molds to bioprinted scaffolds, will potentially enhance the printing experience with soft bioinks while preserving cell durability and viability. 

Keywords
3D Bioprinting
Vat polymerization
Tissue engineering
3D molds
Peptide hydrogels
Soft bioinks
References
[1]

Murphy SV, Atala A, 2014, 3D bioprinting of tissues and organs. Nat Biotechnol, 32: 773–785. https://doi.org/10.1038/nbt.2958

[2]

Jiang T, Munguia-Lopez JG, Flores-Torres S, et al. 2019, Extrusion bioprinting of soft materials: An emerging technique for biological model fabrication. Appl Phys Rev, 6: 011310. https://doi.org/10.1063/1.5059393

[3]

Li X, Liu B, Pei B, et al., 2020, Inkjet bioprinting of biomaterials. Chem Rev, 120: 10793-10833. https://doi.org/10.1021/acs.chemrev.0c00008

[4]

Ng WL, Lee JM, Yeong WY, et al., 2017, Microvalve-based bioprinting-process, bio-inks and applications. Biomater Sci, 5: 632–647.

[5]

Dou C, Perez V, Qu J, et al., 2021, A state‐of‐the‐art review of laser‐assisted bioprinting and its future research trends. Chem Bio Eng Rev, 8: 517–534. https://doi.org/10.1002/cben.202000037

[6]

Ng WL, Lee JM, Zhou M, et al., 2020, Vat polymerization-based bioprinting process, materials, applications and regulatory challenges. Biofabrication, 12: 022001. https://doi.org/10.1088/1758-5090/ab6034

[7]

Li W, Mille LS, Robledo JA, et al., 2020, Recent advances in formulating and processing biomaterial inks for vat polymerization‐based 3D printing. Adv Healthc Mater, 9: 2000156. https://doi.org/10.1002/adhm.202000156

[8]

Ahangar P, Cooke ME, Weber MH, et al., 2019. Current biomedical applications of 3D printing and additive manufacturing. Appl Sci, 9: 1713.

[9]

Guzzi EA, Tibbitt MW, 2020, Additive manufacturing of precision biomaterials. Adv Mater, 32: 1901994.

[10]

Albalawi HI, Khan ZN, Valle-Pérez AU, et al., 2021, Sustainable and eco-friendly coral restoration through 3d printing and fabrication. ACS Sustain Chem Eng, 9: 12634-12645.

[11]

Sasmal P, Datta P, Wu Y, et al., 2018, 3D bioprinting for modelling vasculature. Microphysiol Syst, 2: 9. https://doi.org/10.21037/mps.2018.10.02

[12]

Janarthanan G, Shin HS, Kim IG, et al., 2020, Self-crosslinking hyaluronic acid–carboxymethylcellulose hydrogel enhances multilayered 3D-printed construct shape integrity and mechanical stability for soft tissue engineering. Biofabrication, 12: 045026. https://doi.org/10.1088/1758-5090/aba2f7

[13]

Gopinathan J, Noh I, 2018, Recent trends in bioinks for 3D printing. Biomater Res, 22: 11.

[14]

Avila-Ramírez A, Valle-Pérez AU, Susapto HH, et al., 2021, Ecologically friendly biofunctional ink for reconstruction of rigid living systems under wet conditions. In J Bioprint, 7: 398. https://doi.org/10.18063/ijb.v7i4.398

[15]

Tirella A, Orsini A, Vozzi G, et al., 2009, A phase diagram for microfabrication of geometrically controlled hydrogel scaffolds. Biofabrication, 1: 045002. https://doi.org/10.1088/1758-5082/1/4/045002

[16]

Poldervaart MT, Goversen B, de Ruijter M, et al., 2017, 3D bioprinting of methacrylated hyaluronic acid (MeHA) hydrogel with intrinsic osteogenicity. PLoS One, 12: e0177628. https://doi.org/10.1371/journal.pone.0177628

[17]

Susapto HH, Alhattab D, Abdelrahman S, et al., 2021, Ultrashort peptide bioinks support automated printing of large-scale constructs assuring long-term survival of printed tissue constructs. Nano Lett, 21: 2719–2729. https://doi.org/10.1021/acs.nanolett.0c04426

[18]

Hauser CA, Deng R, Mishra A, et al., 2011, Natural tri- to hexapeptides self-assemble in water to amyloid β-type fiber aggregates by unexpected á-helical intermediate structures. Proc Natl Acad Sci, 108: 1361–1366. https://doi.org/10.1073/pnas.1014796108

[19]

Loo Y, Lakshmanan A, Ni M, et al., 2015, Peptide bioink: Self-assembling nanofibrous scaffolds for three-dimensional organotypic cultures. Nano Lett, 15: 6919–6925. https://doi.org/10.1021/acs.nanolett.5b02859

[20]

Advincula RC, Dizon JR, Caldona EB, et al., 2021, On the progress of 3D-printed hydrogels for tissue engineering. MRS Commun, 11: 539–553. https://doi.org/10.1557/s43579-021-00069-1

[21]

Spicer CD, 2020, Hydrogel scaffolds for tissue engineering: The importance of polymer choice. Polym Chem, 11: 184–219.

[22]

Naahidi S, Jafari M, Logan M, et al., 2017, Biocompatibility of hydrogel-based scaffolds for tissue engineering applications. Biotechnol Adv, 35: 530-544. https://doi.org/10.1016/j.biotechadv.2017.05.006

[23]

Khansari MM, Sorokina LV, Mukherjee P, et al., 2017, Classification of hydrogels based on their source: A review and application in stem cell regulation. JOM, 69: 1340–1347. https://doi.org/10.1007/s11837-017-2412-9

[24]

Anandakrishnan N, Ye H, Guo Z, et al., 2020, Fast 3D printing of large-scale biocompatible hydrogel models. BioRxiv, 2020: 345660. https://doi.org/10.1101/2020.10.22.345660

[25]

Morioka M, Sakakibara S, 2010, A new cell production assembly system with human-robot cooperation. CIRP Ann, 59: 9–12.

[26]

Bhatt PM, Malhan RK, Shembekar AV, et al., 2020, Expanding capabilities of additive manufacturing through use of robotics technologies: A survey. Addit Manuf, 31: 100933. https://doi.org/10.1016/j.addma.2019.100933

[27]

Urhal P, Weightman A, Diver C, et al., 2019, Robot assisted additive manufacturing: A review. Robot. Comput Integr Manuf, 59: 335-345. https://doi.org/10.1016/j.rcim.2019.05.005

[28]

Song X, Pan Y, Chen Y, 2015, Development of a low-cost parallel kinematic machine for multidirectional additive manufacturing. J Manuf Sci Eng, 137: 021005. https://doi.org/10.1115/1.4028897

[29]

Alrashoudi AA, Albalawi HI, Aldoukhi AH, et al., 2021, Fabrication of a lateral flow assay for rapid in-field detection of COVID-19 antibodies using additive manufacturing printing technologies. Int J Bioprint, 7: 399. https://doi.org/10.18063/ijb.v7i4.399

[30]

Khan Z, Kahin K, Rauf S, et al., 2018, Optimization of a 3D bioprinting process using ultrashort peptide bioinks. Int J Bioprint, 5: 173. https://doi.org/10.18063/ijb.v5i1.173

[31]

Kahin K, Khan Z, Albagami M, et al., 2019, Development of a robotic 3D bioprinting and microfluidic pumping system for tissue and organ engineering. In: Gray BL, Becker H, editors. Microfluidics, BioMEMS, and Medical Microsystems XVII (SPIE, 2019). https://doi.org/10.1117/12.2507237

[32]

Khan Z, Kahin K, Hauser C, 2021, Time-dependent pulsing of microfluidic pumps to enhance 3D bioprinting of peptide bioinks. In: Gray BL, Becker H, editors. Microfluidics, BioMEMS, and Medical Microsystems XIX (SPIE, 2021). https://doi.org/10.1117/12.2578830

[33]

Ng WL, Chua CK, Shen YF, 2019, Print me an organ! Why we are not there yet. Prog Polym Sci, 97: 101145. https://doi.org/10.1016/j.progpolymsci.2019.101145

[34]

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. https://doi.org/10.1126/sciadv.1500758

Share
Back to top
Materials Science in Additive Manufacturing, Electronic ISSN: 2810-9635 Published by AccScience Publishing