While three-dimensional (3D) printing of biological matter is of increasing interest, current linear 3D printing processes lack the efficiency at scale required to mass manufacture products made of biological matter. This paper introduces a device for a newly developed parallel additive manufacturing technology for production of 3D objects, which addresses the need for faster, industrial scale additive manufacturing methods. The technology uses multilayer cryolithography (MLCL) to make biological products faster and in larger quantities by simultaneously printing two-dimensional (2D) layers in parallel and assembling the layers into a 3D structure at an assembly site, instead of sequentially and linearly assembling a 3D object from individual elements as in conventional 3D printing. The technique uses freezing to bind the 2D layers together into a 3D object. This paper describes the basic principles of MLCL and demonstrates the technology with a new device used to manufacture a very simple product that could be used for tissue engineering, as an example. An evaluation of the interlayer bonding shows that a continuous and coherent structure can be made from the assembly of distinct layers using MLCL.

References

1.
Giwa
,
S.
,
Lewis
,
J. K.
,
Alvarez
,
L.
,
Langer
,
R.
,
Roth
,
A. E.
,
Church
,
G. M.
,
Markmann
,
J. F.
,
Sachs
,
D. H.
,
Chandraker
,
A.
,
Wertheim
,
J. A.
,
Rothblatt
,
M.
,
Boyden
,
E. S.
,
Eidbo
,
E.
,
Lee
,
W. P. A.
,
Pomahac
,
B.
,
Brandacher
,
G.
,
Weinstock
,
D. M.
,
Elliott
,
G.
,
Nelson
,
D.
,
Acker
,
J. P.
,
Uygun
,
K.
,
Schmalz
,
B.
,
Weegman
,
B. P.
,
Tocchio
,
A.
,
Fahy
,
G. M.
,
Storey
,
K. B.
,
Rubinsky
,
B.
,
Bischof
,
J.
,
Elliott
,
J. A. W.
,
Woodruff
,
T. K.
,
Morris
,
G. J.
,
Demirci
,
U.
,
Brockbank
,
K. G. M.
,
Woods
,
E. J.
,
Ben
,
R. N.
,
Baust
,
J. G.
,
Gao
,
D.
,
Fuller
,
B.
,
Rabin
,
Y.
,
Kravitz
,
D. C.
,
Taylor
,
M. J.
, and
Toner
,
M.
,
2017
, “
The Promise of Organ and Tissue Preservation to Transform Medicine
,”
Nat. Biotechnol.
,
35
(
6
), pp.
530
542
.
2.
Nerem
,
R. M.
, and
Sambanis
,
A.
,
1995
, “
Tissue Engineering: From Biology to Biological Substitutes
,”
Tissue Eng.
,
1
(
1
), pp.
3
13
.
3.
Khademhosseini
,
A.
, and
Langer
,
R.
,
2016
, “
A Decade of Progress in Tissue Engineering
,”
Nat. Protoc.
,
11
(
10
), pp.
1775
1781
.
4.
Caplin
,
J. D.
,
Granados
,
N. G.
,
James
,
M. R.
,
Montazami
,
R.
, and
Hashemi
,
N.
,
2015
, “
Microfluidic Organ-on-a-Chip Technology for Advancement of Drug Development and Toxicology
,”
Adv. Healthcare Mater.
,
4
(
10
), pp.
1426
1450
.
5.
Ozbolat
,
I. T.
, and
Yu
,
Y.
,
2013
, “
Bioprinting Toward Organ Fabrication: Challenges and Future Trends
,”
IEEE Trans. Biomed. Eng.
,
60
(
3
), pp.
691
699
.
6.
Murphy
,
S. V.
, and
Atala
,
A.
,
2014
, “
3D Bioprinting of Tissues and Organs
,”
Nat. Biotechnol.
,
32
(
8
), pp.
773
785
.
7.
An
,
J.
,
Teoh
,
J. E. M.
,
Suntornnond
,
R.
, and
Chua
,
C. K.
,
2015
, “
Design and 3D Printing of Scaffolds and Tissues
,”
Eng.
,
1
(
2
), pp.
261
268
.
8.
Do
,
A. V.
,
Khorsand
,
B.
,
Geary
,
S. M.
, and
Salem
,
A. K.
,
2015
, “
3D Printing of Scaffolds for Tissue Regeneration Applications
,”
Adv. Healthcare Mater.
,
4
(
12
), pp.
1742
1762
.
9.
Hollister
,
S. J.
,
2005
, “
Porous Scaffold Design for Tissue Engineering
,”
Nat. Mater.
,
4
(
7
), pp.
518
524
.
10.
Kang
,
H. W.
,
Kengla
,
C.
,
Lee
,
S. J.
,
Yoo
,
J. J.
, and
Atala
,
A.
,
2014
, “
3-D Organ Printing Technologies for Tissue Engineering Applications
,”
Rapid Prototyping Biomater.: Princ. Appl.
, pp.
236
253
.
11.
Francoise
,
M.
,
Karoly
,
J.
,
Chirag
,
K.
,
Benjamin
,
S.
,
Scott
,
D.
,
Bradley
,
H.
,
Stephen
,
C.
, and
Forgacs
,
G.
,
2012
, “
Toward Engineering Functional Organ Modules by Additive Manufacturing
,”
Biofabrication
,
4
(
2
), p.
022001
.
12.
Tan
,
Z.
,
Parisi
,
C.
,
Di Silvio
,
L.
,
Dini
,
D.
, and
Forte
,
A. E.
,
2017
, “
Cryogenic 3D Printing of Super Soft Hydrogels
,”
Sci. Rep.
,
7
(
1
), p.
16293
.
13.
Adamkiewicz
,
M.
, and
Rubinsky
,
B.
,
2015
, “
Cryogenic 3D Printing for Tissue Engineering
,”
Cryobiology
,
71
(
3
), pp.
518
521
.
14.
Pham
,
C. B.
,
Leong
,
K. F.
,
Lim
,
T. C.
, and
Chian
,
K. S.
,
2008
, “
Rapid Freeze Prototyping Technique in Bio-Plotters for Tissue Scaffold Fabrication
,”
Rapid Prototyp. J.
,
14
(
4
), pp.
246
253
.
15.
Kim
,
G.
,
Ahn
,
S.
,
Yoon
,
H.
,
Kim
,
Y.
, and
Chun
,
W.
,
2009
, “
A Cryogenic Direct-Plotting System for Fabrication of 3D Collagen Scaffolds for Tissue Engineering
,”
J. Mater. Chem.
,
19
(
46
), pp.
8817
8823
.
16.
Wang
,
C.
,
Zhao
,
Q.
, and
Wang
,
M.
,
2017
, “
Cryogenic 3D Printing for Producing Hierarchical Porous and RhBMP-2-Loaded Ca-P/PLLA Nanocomposite Scaffolds for Bone Tissue Engineering
,”
Biofabrication
,
9
(
2
), p.
025031
.
17.
Cohen
,
D. L.
,
Malone
,
E.
,
Lipson
,
H.
, and
Bonassar
,
L. J.
,
2006
, “
Direct Freeform Fabrication of Seeded Hydrogels in Arbitrary Geometries
,”
Tissue Eng.
,
12
(
5
), pp.
1325
1335
.
18.
Lee
,
V. K.
, and
Dai
,
G.
,
2017
, “
Printing of Three-Dimensional Tissue Analogs for Regenerative Medicine
,”
Ann. Biomed. Eng.
,
45
(
1
), pp.
115
131
.
19.
Holweg
,
M.
,
2015
, “
The Limits of 3D Printing
,”
Harvard Business Review
,
Harvard Business Publishing
,
Boston, MA
, p.
5
.
20.
Zawada
,
B.
,
Ukpai
,
G.
,
Powell-Palm
,
M. J.
, and
Rubinsky
,
B.
,
2018
, “
Multi-Layer Cryolithography for Additive Manufacturing
,”
Prog. Addit. Manuf.
,
3
(
4
), pp.
245
255
.
21.
Liao
,
C.-Y.
,
Wu
,
W.-J.
,
Hsieh
,
C.-T.
,
Tseng
,
C.-S.
,
Dai
,
N.-T.
, and
Hsu
,
S.
,
2016
, “
Design and Development of a Novel Frozen-Form Additive Manufacturing System for Tissue Engineering Applications
,”
3D Print. Addit. Manuf.
,
3
(
4
), pp.
216
225
.
22.
Putnik
,
G.
,
Sluga
,
A.
,
ElMaraghy
,
H.
,
Teti
,
R.
,
Koren
,
Y.
,
Tolio
,
T.
, and
Hon
,
B.
,
2013
, “
Scalability in Manufacturing Systems Design and Operation: State-of-the-Art and Future Developments Roadmap
,”
CIRP Ann. Manuf. Technol.
,
62
(
2
), pp.
751
774
.
23.
Feygin
,
M.
,
1989
, “
Laminated Object Manufacturing (LOM): A Simpler Process
,”
Nat. Conf. on Rapid Prototyping
, pp.
6365
.
24.
Lee
,
K. Y.
, and
Mooney
,
D. J.
,
2012
, “
Alginate: Properties and Biomedical Applications
,”
Prog. Polym. Sci.
,
37
(
1
), pp.
106
126
.
25.
Andersen
,
T.
,
Strand
,
B. L.
,
Formo
,
K.
,
Alsberg
,
E.
, and
Christensen
,
B. E.
,
2011
, “
Alginates as Biomaterials in Tissue Engineering
,”
Carbohydr. Chem.
,
37
, pp.
227
258
.
26.
Augst
,
D. A.
,
Kong Joon
,
H.
, and
Mooney
,
J. D.
,
2006
, “
Alginate Hydrogels as Biomaterials
,”
Macromol. Biosci.
,
6
(
8
), pp.
623
633
.
27.
David
,
W.
, and
Hahn
,
M. N. Ö.
,
2012
, “
Phase-Change Problems
,”
Heat Conduction
, 3rd ed.,
Wiley
,
Hoboken, NJ
, pp.
452
495
.
28.
Preciado
,
J. A.
,
Skandakumaran
,
P.
,
Cohen
,
S.
, and
Rubinsky
,
B.
,
2003
, “
Utilization of Directional Freezing for the Construction of Tissue Engineering Scaffolds
,” ASME Paper No. IMECE2003-42067.
29.
Peng
,
Z. F.
,
Shi
,
S. L.
,
Jin
,
H. X.
,
Yao
,
G. D.
,
Wang
,
E. Y.
,
Yang
,
H. Y.
,
Song
,
W. Y.
, and
Sun
,
Y. P.
,
2015
, “
Impact of Oxygen Concentrations on Fertilization, Cleavage, Implantation, and Pregnancy Rates of In Vivo Generated Human Embryos
,”
Int. J. Clin. Exp. Med.
,
8
(
4
), pp.
6179
6185
.
30.
Avti
,
P. K.
,
Patel
,
S. C.
,
Uppal
,
P.
,
O'Malley
,
G.
,
Garlow
,
J.
, and
Sitharaman
,
B.
,
2012
, “
Nanobiomaterials for Tissue Engineering
,”
Tissue Eng.: Princ. Pract.
, pp.
11-1
11–24
.
31.
Shapiro
,
L.
, and
Cohen
,
S.
,
1997
, “
Novel Alginate Sponges for Cell Culture and Transplantation
,”
Biomaterials
,
18
(
8
), pp.
583
590
.
32.
Mahler
,
S.
,
Desille
,
M.
,
Frémond
,
B.
,
Chesné
,
C.
,
Guillouzo
,
A.
,
Campion
,
J. P.
, and
Clément
,
B.
,
2003
, “
Hypothermic Storage and Cryopreservation of Hepatocytes: The Protective Effect of Alginate Gel Against Cell Damages
,”
Cell Transplant.
,
12
(
6
), pp.
579
592
.
33.
Xiong
,
Z.
,
Yan
,
Y. N.
,
Wang
,
S. G.
,
Zhang
,
R. J.
, and
Zhang
,
C.
,
2002
, “
Fabrication of Porous Scaffolds for Bone Tissue Engineering Via Low-Temperature Deposition
,”
Scr. Mater.
,
46
(
11
), pp.
771
776
.
34.
Liu
,
L.
,
Xiong
,
Z.
,
Yan
,
Y.
,
Zhang
,
R.
,
Wang
,
X.
, and
Jin
,
L.
,
2009
, “
Multinozzle Low-Temperature Deposition System for Construction of Gradient Tissue Engineering Scaffolds
,”
J. Biomed. Mater. Res., Part B
,
88
(
1
), pp.
254
263
.
35.
Yen
,
H. J.
,
Hsu
,
S. H.
,
Tseng
,
C. S.
,
Huang
,
J. P.
, and
Tsai
,
C. L.
,
2009
, “
Fabrication of Precision Scaffolds Using Liquid-Frozen Deposition Manufacturing for Cartilage Tissue Engineering
,”
Tissue Eng., Part A
,
15
(
5
), pp.
965
975
.
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