Many recently developed 3D bioprinting strategies operate by extruding aqueous biopolymer solutions directly into a variety of different support materials constituted from swollen, solvated, aqueous, polymer assemblies. In developing these 3D printing methods and materials, great care is often taken to tune the rheological behaviors of both inks and 3D support media. By contrast, much less attention has been given to the physics of the interfaces created when structuring one polymer phase into another in embedded 3D printing applications. For example, it is currently unclear whether a dynamic interfacial tension between miscible phases stabilizes embedded 3D bioprinted structures as they are shaped while in a liquid state. Interest in the physics of interfaces between complex fluids has grown dramatically since the discovery of liquid–liquid phase separation (LLPS) in living cells. We believe that many new insights coming from this burst of investigation into LLPS within biological contexts can be leveraged to develop new materials and methods for improved 3D bioprinting that leverage LLPS in mixtures of biopolymers, biocompatible synthetic polymers, and proteins. Thus, in this review article, we highlight work at the interface between recent LLPS research and embedded 3D bioprinting methods and materials, and we introduce a 3D bioprinting method that leverages LLPS to stabilize printed biopolymer inks embedded in a bioprinting support material.
References
1.
I.
Matai
, G.
Kaur
, A.
Seyedsalehi
, A.
McClinton
, and C. T.
Laurencin
, Biomaterials
226
, 119536
(2020
).2.
C. S.
O'Bryan
, T.
Bhattacharjee
, S. R.
Niemi
, S.
Balachandar
, N.
Baldwin
, S. T.
Ellison
, C. R.
Taylor
, W. G.
Sawyer
, and T. E.
Angelini
, MRS Bull.
42
(8
), 571
–577
(2017
).3.
Y.
Jin
, D.
Zhao
, and Y.
Huang
, Bio-Des. Manuf.
1
(2
), 123
–134
(2018
).4.
Y.
Jin
, Y.
Shen
, J.
Yin
, J.
Qian
, and Y.
Huang
, ACS Appl. Mater. Interfaces
10
(12
), 10461
–10470
(2018
).5.
Y.
Jiang
, J.
Zhou
, Z.
Yang
, D.
Liu
, X.
Xv
, G.
Zhao
, H.
Shi
, and Q.
Zhang
, J. Mater. Sci.
53
(16
), 11883
–11900
(2018
).6.
T.
Bhattacharjee
, C. J.
Gil
, S. L.
Marshall
, J. M.
Urueña
, C. S.
O'Bryan
, M.
Carstens
, B.
Keselowsky
, G. D.
Palmer
, S.
Ghivizzani
, and C. P.
Gibbs
, ACS Biomater. Sci. Eng.
2
(10
), 1787
–1795
(2016
).7.
C. D.
Morley
, S. T.
Ellison
, T.
Bhattacharjee
, C. S.
O'Bryan
, Y.
Zhang
, K. F.
Smith
, C. P.
Kabb
, M.
Sebastian
, G. L.
Moore
, and K. D.
Schulze
, Nat. Commun.
10
(1
), 3029
(2019
).8.
T. J.
Hinton
, Q.
Jallerat
, R. N.
Palchesko
, J. H.
Park
, M. S.
Grodzicki
, H.-J.
Shue
, M. H.
Ramadan
, A. R.
Hudson
, and A. W.
Feinberg
, Sci. Adv.
1
(9
), e1500758
(2015
).9.
Y.
Jin
, A.
Compaan
, T.
Bhattacharjee
, and Y.
Huang
, Biofabrication
8
(2
), 025016
(2016
).10.
C. S.
O'Bryan
, T.
Bhattacharjee
, S.
Hart
, C. P.
Kabb
, K. D.
Schulze
, I.
Chilakala
, B. S.
Sumerlin
, W. G.
Sawyer
, and T. E.
Angelini
, Sci. Adv.
3
(5
), e1602800
(2017
).11.
T.
Bhattacharjee
, S. M.
Zehnder
, K. G.
Rowe
, S.
Jain
, R. M.
Nixon
, W. G.
Sawyer
, and T. E.
Angelini
, Sci. Adv.
1
(8
), e1500655
(2015
).12.
W.
Wu
, A.
DeConinck
, and J. A.
Lewis
, Adv. Mater.
23
(24
), H178
–H183
(2011
).13.
M.
Rocca
, A.
Fragasso
, W.
Liu
, M. A.
Heinrich
, and Y. S.
Zhang
, SLAS Technol.
23
(2
), 154
–163
(2018
).14.
C. B.
Highley
, C. B.
Rodell
, and J. A.
Burdick
, Adv. Mater.
27
(34
), 5075
–5079
(2015
).15.
C. B.
Rodell
, A. L.
Kaminski
, and J. A.
Burdick
, Biomacromolecules
14
(11
), 4125
–4134
(2013
).16.
C. P.
Brangwynne
, C. R.
Eckmann
, D. S.
Courson
, A.
Rybarska
, C.
Hoege
, J.
Gharakhani
, F.
Jülicher
, and A. A.
Hyman
, Science
324
(5935
), 1729
–1732
(2009
).17.
Y.
Shin
and C. P.
Brangwynne
, Science
357
(6357
), eaaf4382
(2017
).18.
C. P.
Brangwynne
, P.
Tompa
, and R. V.
Pappu
, Nat. Phys.
11
(11
), 899
–904
(2015
).19.
T.
Yoshizawa
, R.-S.
Nozawa
, T. Z.
Jia
, T.
Saio
, and E.
Mori
, Biophys. Rev.
12
(2
), 519
–539
(2020
).20.
Q.
Li
, X.
Peng
, Y.
Li
, W.
Tang
, J. a
Zhu
, J.
Huang
, Y.
Qi
, and Z.
Zhang
, Nucleic Acids Res.
48
(D1
), D320
–D327
(2020
).21.
S.
Deshpande
and C.
Dekker
, Curr. Opin. Colloid Interface Sci.
52
, 101419
(2021
).22.
C.
Roden
and A. S.
Gladfelter
, Nat. Rev. Mol. Cell Biol.
22
(3
), 183
–195
(2021
).23.
D. R.
Scheff
, K. L.
Weirich
, K.
Dasbiswas
, A.
Patel
, S.
Vaikuntanathan
, and M. L.
Gardel
, Soft Matter
16
(24
), 5659
–5668
(2020
).24.
K. L.
Weirich
, S.
Banerjee
, K.
Dasbiswas
, T. A.
Witten
, S.
Vaikuntanathan
, and M. L.
Gardel
, Proc. Natl. Acad. Sci.
114
(9
), 2131
–2136
(2017
).25.
K. L.
Weirich
, K.
Dasbiswas
, T. A.
Witten
, S.
Vaikuntanathan
, and M. L.
Gardel
, Proc. Natl. Acad. Sci.
116
(23
), 11125
–11130
(2019
).26.
R. W.
Style
, T.
Sai
, N.
Fanelli
, M.
Ijavi
, K.
Smith-Mannschott
, Q.
Xu
, L. A.
Wilen
, and E. R.
Dufresne
, Phys. Rev. X
8
(1
), 011028
(2018
).27.
K. A.
Rosowski
, T.
Sai
, E.
Vidal-Henriquez
, D.
Zwicker
, R. W.
Style
, and E. R.
Dufresne
, Nat. Phys.
16
, 422
–425
(2020
).28.
29.
D.
Truzzolillo
and L.
Cipelletti
, Soft Matter
13
(1
), 13
–21
(2017
).30.
C. S.
O'Bryan
, A.
Brady-Mine
, C. J.
Tessmann
, A. M.
Spotz
, and T. E.
Angelini
, Soft Matter
17
(14
), 3886
–3894
(2021
).31.
T. J.
Hinton
, A.
Hudson
, K.
Pusch
, A.
Lee
, and A. W.
Feinberg
, ACS Biomater. Sci. Eng.
2
(10
), 1781
–1786
(2016
).32.
C. S.
O'Bryan
, T.
Bhattacharjee
, S. L.
Marshall
, W. G.
Sawyer
, and T. E.
Angelini
, Bioprinting
11
, e00037
(2018
).33.
E.
Pairam
, H.
Le
, and A.
Fernández-Nieves
, Phys. Rev. E
90
(2
), 021002
(2014
).34.
S. E.
May
and J. V.
Maher
, Phys. Rev. Lett.
67
(15
), 2013
–2016
(1991
).35.
C. R.
Mace
, O.
Akbulut
, A. A.
Kumar
, N. D.
Shapiro
, R.
Derda
, M. R.
Patton
, and G. M.
Whitesides
, J. Am. Chem. Soc.
134
(22
), 9094
–9097
(2012
).36.
D.
Forciniti
, C.
Hall
, and M.
Kula
, J. Biotechnol.
16
(3–4
), 279
–296
(1990
).37.
E.
Atefi
, J. A.
Mann
, Jr., and H.
Tavana
, Langmuir
30
(32
), 9691
–9699
(2014
).38.
Y.
Liu
, R.
Lipowsky
, and R.
Dimova
, Langmuir
28
(8
), 3831
–3839
(2012
).39.
D.
Petrak
, E.
Atefi
, L.
Yin
, W.
Chilian
, and H.
Tavana
, Biotechnol. Bioeng.
111
(2
), 404
–412
(2014
).40.
H.
Tavana
, B.
Mosadegh
, and S.
Takayama
, Adv. Mater.
22
(24
), 2628
–2631
(2010
).41.
G.
Luo
, Y.
Yu
, Y.
Yuan
, X.
Chen
, Z.
Liu
, and T.
Kong
, Adv. Mater.
31
(49
), 1904631
(2019
).42.
H.
Kusumaatmaja
, Y.
Li
, R.
Dimova
, and R.
Lipowsky
, Phys. Rev. Lett.
103
(23
), 238103
(2009
).43.
J.
Ryden
and P.—a.
Albertsson
, J. Colloid Interface Sci.
37
(1
), 219
–222
(1971
).44.
S.
Elbaum-Garfinkle
, Y.
Kim
, K.
Szczepaniak
, C. C.-H.
Chen
, C. R.
Eckmann
, S.
Myong
, and C. P.
Brangwynne
, Proc. Natl. Acad. Sci.
112
(23
), 7189
–7194
(2015
).45.
K. H.
Shah
, S. N.
Varia
, L. A.
Cook
, and P. K.
Herman
, PLoS One
11
(6
), e0158776
(2016
).46.
S. L.
Moon
, T.
Morisaki
, A.
Khong
, K.
Lyon
, R.
Parker
, and T. J.
Stasevich
, Nat. Cell Biol.
21
(2
), 162
–168
(2019
).47.
N.
Kedersha
, G.
Stoecklin
, M.
Ayodele
, P.
Yacono
, J.
Lykke-Andersen
, M. J.
Fritzler
, D.
Scheuner
, R. J.
Kaufman
, D. E.
Golan
, and P.
Anderson
, J. Cell Biol.
169
(6
), 871
–884
(2005
).48.
D. W.
Sanders
, N.
Kedersha
, D. S.
Lee
, A. R.
Strom
, V.
Drake
, J. A.
Riback
, D.
Bracha
, J. M.
Eeftens
, A.
Iwanicki
, and A.
Wang
, Cell
181
(2
), 306
–324.e28
(2020
).49.
C. P.
Brangwynne
, T. J.
Mitchison
, and A. A.
Hyman
, Proc. Natl. Acad. Sci.
108
(11
), 4334
–4339
(2011
).50.
F.-M.
Boisvert
, S.
van Koningsbruggen
, J.
Navascués
, and A. I.
Lamond
, Nat. Rev. Mol. Cell Biol.
8
(7
), 574
–585
(2007
).51.
S.
Jain
, J. R.
Wheeler
, R. W.
Walters
, A.
Agrawal
, A.
Barsic
, and R.
Parker
, Cell
164
(3
), 487
–498
(2016
).52.
A.
Hubstenberger
, S. L.
Noble
, C.
Cameron
, and T. C.
Evans
, Dev. Cell
27
(2
), 161
–173
(2013
).53.
M.
Feric
, N.
Vaidya
, T. S.
Harmon
, D. M.
Mitrea
, L.
Zhu
, T. M.
Richardson
, R. W.
Kriwacki
, R. V.
Pappu
, and C. P.
Brangwynne
, Cell
165
(7
), 1686
–1697
(2016
).54.
L. M.
Jawerth
, M.
Ijavi
, M.
Ruer
, S.
Saha
, M.
Jahnel
, A. A.
Hyman
, F.
Jülicher
, and E.
Fischer-Friedrich
, Phys. Rev. Lett.
121
(25
), 258101
(2018
).55.
M.
Ijavi
, R. W.
Style
, L.
Emmanouilidis
, A.
Kumar
, S. M.
Meier
, A. L.
Torzynski
, F. H.
Allain
, Y.
Barral
, M. O.
Steinmetz
, and E. R.
Dufresne
, Soft Matter
17
(6
), 1655
–1662
(2021
).56.
A.
Zbinden
, M.
Pérez-Berlanga
, P. D.
Rossi
, and M.
Polymenidou
, Dev. Cell
55
(1
), 45
–68
(2020
).57.
N. M.
Kanaan
, C.
Hamel
, T.
Grabinski
, and B.
Combs
, Nat. communications
11
(1
), 2809
(2020
).58.
S.
Ray
, N.
Singh
, R.
Kumar
, K.
Patel
, S.
Pandey
, D.
Datta
, J.
Mahato
, R.
Panigrahi
, A.
Navalkar
, and S.
Mehra
, Nat. Chem.
12
(8
), 705
–716
(2020
).59.
M. C.
Hardenberg
, T.
Sinnige
, S.
Casford
, S. T.
Dada
, C.
Poudel
, E. A.
Robinson
, M.
Fuxreiter
, C. F.
Kaminksi
, G. S.
Kaminski Schierle
, and E. A.
Nollen
, J. Mol. Cell Biol.
13
(4
), 282
–294
(2021
).60.
S.
Ambadipudi
, J.
Biernat
, D.
Riedel
, E.
Mandelkow
, and M.
Zweckstetter
, Nat. Commun.
8
(1
), 275
(2017
).61.
A.
Siegert
, M.
Rankovic
, F.
Favretto
, T.
Ukmar‐Godec
, T.
Strohäker
, S.
Becker
, and M.
Zweckstetter
, Protein Sci.
30
(7
), 1326
–1336
(2021
).62.
A. A.
André
and E.
Spruijt
, Int. J. Mol. Sci.
21
(16
), 5908
(2020
).63.
S.
Singh
and H.
Tavana
, Front. Chem.
6
, 379
(2018
).64.
Y.
Xu
, R.
Qi
, H.
Zhu
, B.
Li
, Y.
Shen
, G.
Krainer
, D.
Klenerman
, and T. P.
Knowles
, Adv. Mater.
33
(33
), 2008670
(2021
).65.
Y.
Zhang
, S. T.
Ellison
, S.
Duraivel
, C. D.
Morley
, C. R.
Taylor
, and T. E.
Angelini
, Bioprinting
21
, e00121
(2021
).66.
67.
T.
Bhattacharjee
, D. B.
Amchin
, J. A.
Ott
, F.
Kratz
, and S. S.
Datta
, Biophys. J.
120
, 3483
(2021
).68.
D.
Chahal
, A.
Ahmadi
, and K. C.
Cheung
, Biotechnol. Bioeng.
109
(11
), 2932
–2940
(2012
).69.
T.
Uchida
and H.
Onoe
, Micromachines
10
(7
), 433
(2019
).70.
L. A.
Hockaday
, K. H.
Kang
, N. W.
Colangelo
, P. Y. C.
Cheung
, B.
Duan
, E.
Malone
, J.
Wu
, L. N.
Girardi
, L. J.
Bonassar
, H.
Lipson
, C. C.
Chu
, and J. T.
Butcher
, Biofabrication
4
(3
), 035005
(2012
).71.
N. E.
Fedorovich
, J. R.
De Wijn
, A. J.
Verbout
, J.
Alblas
, and W. J. A.
Dhert
, Tissue Eng., Part A
14
(1
), 127
–133
(2008
).72.
I. T.
Ozbolat
and M.
Hospodiuk
, Biomaterials
76
, 321
–343
(2016
).73.
A.
Skardal
, J.
Zhang
, L.
McCoard
, X.
Xu
, S.
Oottamasathien
, and G. D.
Prestwich
, Tissue Eng., Part A
16
(8
), 2675
–2685
(2010
).74.
A. G.
Teixeira
, R.
Agarwal
, K. R.
Ko
, J.
Grant-Burt
, B. M.
Leung
, and J. P.
Frampton
, Adv. Healthcare Mater.
7
(6
), 1701036
(2018
).75.
P. Å.
Albertsson
, Partition of Cell Particles and Macromolecules: Distribution and Fractionation of Cells, Viruses, Microsomes, Proteins, Nucleic Acids, and Antigen-Antibody Complexes in Aqueous Polymer Two-Phase Systems
(Wiley
, 1960
).76.
P.-Å.
Albertsson
, Adv. Protein Chem.
24
, 309
–341
(1970
).77.
D.
Forciniti
, C.
Hall
, and M.-R.
Kula
, Fluid Phase Equilib.
61
(3
), 243
–262
(1991
).78.
V.
Cesi
, B.
Katzbauer
, M.
Narodoslawsky
, and A.
Moser
, Int. J. Thermophys.
17
(1
), 127
–135
(1996
).79.
M. W.
Edelman
, E.
Van Der Linden
, and R. H.
Tromp
, Macromolecules
36
(20
), 7783
–7790
(2003
).80.
M.
Vis
, V. F.
Peters
, R. H.
Tromp
, and B. H.
Erné
, Langmuir
30
(20
), 5755
–5762
(2014
).81.
M. S.
Long
, C. D.
Jones
, M. R.
Helfrich
, L. K.
Mangeney-Slavin
, and C. D.
Keating
, Proc. Natl. Acad. Sci.
102
(17
), 5920
–5925
(2005
).82.
C. D.
Keating
, Acc. Chem. Res.
45
(12
), 2114
–2124
(2012
).83.
N.
Martin
, ChemBioChem
20
(20
), 2553
–2568
(2019
).84.
W. M.
Aumiller
, Jr. and C. D.
Keating
, Adv. Colloid Interface Sci.
239
, 75
–87
(2017
).85.
C. D.
Crowe
and C. D.
Keating
, Interface Focus
8
(5
), 20180032
(2018
).86.
S.
Mytnyk
, A. G.
Olive
, F.
Versluis
, J. M.
Poolman
, E.
Mendes
, R.
Eelkema
, and J. H.
van Esch
, Angew. Chem.
129
(47
), 15119
–15123
(2017
).87.
S. D.
Hann
, K. J.
Stebe
, and D.
Lee
, ACS Appl. Mater. Interfaces
9
(29
), 25023
–25028
(2017
).88.
J.
Esquena
, Curr. Opin. Colloid Interface Sci.
25
, 109
–119
(2016
).89.
Y.
Chao
and H. C.
Shum
, Chem. Soc. Rev.
49
(1
), 114
–142
(2020
).90.
S. D.
Hann
, T. H.
Niepa
, K. J.
Stebe
, and D.
Lee
, ACS Appl. Mater. Interfaces
8
(38
), 25603
–25611
(2016
).91.
G.
Xie
, J.
Forth
, Y.
Chai
, P. D.
Ashby
, B. A.
Helms
, and T. P.
Russell
, Chem
5
(10
), 2678
–2690
(2019
).92.
A. V.
Mironov
, O. A.
Mironova
, M. A.
Syachina
, and V. K.
Popov
, Polymer
182
, 121845
(2019
).93.
K. H.
Song
, C. B.
Highley
, A.
Rouff
, and J. A.
Burdick
, Adv. Funct. Mater.
28
(31
), 1801331
(2018
).94.
S. C.
Shit
and P.
Shah
, Nat. Acad. Sci. Lett.
36
(4
), 355
–365
(2013
).95.
96.
V. R.
Sastri
, Plastics in Medical Devices: Properties, Requirements, and Applications
(William Andrew
, 2021
).97.
M.
Zare
, E. R.
Ghomi
, P. D.
Venkatraman
, and S.
Ramakrishna
, J. Appl. Polym. Sci.
138
, 50969
(2021
).98.
V.
Ozbolat
, M.
Dey
, B.
Ayan
, A.
Povilianskas
, M. C.
Demirel
, and I. T.
Ozbolat
, ACS Biomater. Sci. Eng.
4
(2
), 682
–693
(2018
).99.
P.
Huang
, Z.
Xia
, and S.
Cui
, Mater. Des.
142
, 11
–21
(2018
).100.
L.-y.
Zhou
, Q.
Gao
, J.-z.
Fu
, Q.-y.
Chen
, J.-p.
Zhu
, Y.
Sun
, and Y.
He
, ACS Appl. Mater. Interfaces
11
(26
), 23573
–23583
(2019
).101.
L. Y.
Zhou
, J.
Fu
, and Y.
He
, Adv. Funct. Mater.
30
(28
), 2000187
(2020
).102.
B. M.
Rauzan
, A. Z.
Nelson
, S. E.
Lehman
, R. H.
Ewoldt
, and R. G.
Nuzzo
, Adv. Funct. Mater.
28
(21
), 1707032
(2018
).103.
J. T.
Muth
, D. M.
Vogt
, R. L.
Truby
, Y.
Mengüç
, D. B.
Kolesky
, R. J.
Wood
, and J. A.
Lewis
, Adv. Mater.
26
(36
), 6307
–6312
(2014
).104.
K.
Hajash
, B.
Sparrman
, C.
Guberan
, J.
Laucks
, and S.
Tibbits
, 3D Printing Addit. Manuf.
4
(3
), 123
–132
(2017
).105.
S.
Abdollahi
, A.
Davis
, J. H.
Miller
, and A. W.
Feinberg
, PLoS One
13
(4
), e0194890
(2018
).106.
C. M.
Kuo
and S. J.
Clarson
, Macromolecules
25
(8
), 2192
–2195
(1992
).107.
C. M.
Kuo
, S. J.
Clarson
, and J. A.
Semlyen
, Polymer
35
(21
), 4623
–4626
(1994
).108.
C. M.
Kuo
and S. J.
Clarson
, Eur. Polym. J.
29
(5
), 661
–664
(1993
).109.
C. M.
Kuo
and S. J.
Clarson
, Polymer
41
(15
), 5993
–6002
(2000
).110.
A.
Stammer
and B. A.
Wolf
, Macromol. Rapid Commun.
19
, 123
–126
(1998
).111.
H.
Horiuchi
, S.
Irie
, and T.
Nose
, Polymer
32
(11
), 1970
–1974
(1991
).112.
S.
Enders
, A.
Stammer
, and B.
Wolf
, Macromol. Chem. Phys.
197
(9
), 2961
–2972
(1996
).113.
D.
Chopra
, M.
Kontopoulou
, D.
Vlassopoulos
, and S. G.
Hatzikiriakos
, Can. J. Chem. Eng.
80
(6
), 1057
–1064
(2002
).114.
A. R.
Imre
, T.
Kraska
, and L. V.
Yelash
, Phys. Chem. Chem. Phys.
4
(6
), 992
–1001
(2002
).115.
A.
Stammer
and B. A.
Wolf
, Polymer
39
(10
), 2065
–2067
(1998
).116.
P.
Lo Nostro
, Adv. Colloid Interface Sci.
56
, 245
–287
(1995
).117.
P.
Lo Nostro
, a L.
Scalise
, and P.
Baglioni
, J. Chem. Eng. Data
50
(4
), 1148
–1152
(2005
).118.
J. Y.
Kim
, Z.
Liu
, B. M.
Weon
, T.
Cohen
, C.-Y.
Hui
, E. R.
Dufresne
, and R. W.
Style
, Sci. Adv.
6
(13
), eaaz0418
(2020
).119.
R. W.
Style
, R.
Boltyanskiy
, B.
Allen
, K. E.
Jensen
, H. P.
Foote
, J. S.
Wettlaufer
, and E. R.
Dufresne
, Nat. Phys.
11
(1
), 82
–87
(2014
).© 2022 Author(s). Published under an exclusive license by AIP Publishing.
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