Abstract

Pore size and pore interconnectivity that characterize the topology of the vascular networks in tissue constructs are critical to healthy cell behavior and tissue formation. While scaffolds with hollow channel structures (that precede vascularization of tissue engineering constructs) have gained significant attention, still creating the hollow channel networks within various cellular matrices such as cell-laden hydrogels, remain a slow process limited by the speed of material extrusion of 3D printing techniques for the deposition of sacrificial fibers. To address the issue of low throughput for sacrificial fiber production and placement, we propose to utilize the micromanufacturing technique of the immersed microfluidic spinning. This study discusses the optimization of the topology of the sacrificial calcium alginate microfibers as a function of alginate concentration and the gauge of the needle used in the immersed fluidic spinning. An important parameter of the fabricated fiber network is the size of the loops produced via the immersed fluidic spinning. The nutrients should diffuse from the fluidic channel to the center of the loop. We demonstrate that the loops with radii between approximately 1600 and 3200 μm can be produced with needle of 30 gauge for alginate concentrations between 1% and 8%. Fiber diameters are also characterized as a function of needle gauge and alginate concentration. We demonstrate the creation of a hollow channel in a Methacrylate gelatin (GelMA) sample by dissolving the alginate fibers produced via the immersed fluidic spinning method. Finally, viability of the fibroblast cells in GelMA is qualitatively studied as a function of the distance of the cells from the outside boundary of the gel (where the cell media is located). As expected, the cell viability falls as the distance from the outer boundary of the gel increases.

References

1.
Ashammakhi
,
N.
,
GhavamiNejad
,
A.
,
Tutar
,
R.
,
Fricker
,
A.
,
Roy
,
I.
,
Chatzistavrou
,
X.
,
Hoque Apu
,
E.
,
Nguyen
,
K.-L.
,
Ahsan
,
T.
,
Pountos
,
I.
, and
Caterson
,
E. J.
,
2022
, “
Highlights on Advancing Frontiers in Tissue Engineering
,”
Tissue Eng., Part B
,
28
(
3
), pp.
633
664
.10.1089/ten.teb.2021.0012
2.
Cui
,
H.
,
Miao
,
S.
,
Esworthy
,
T.
,
Zhou
,
X.
,
Lee
,
S.
,
Liu
,
C.
,
Yu
,
Z.
,
Fisher
,
J. P.
,
Mohiuddin
,
M.
, and
Zhang
,
L. G.
,
2018
, “
3D Bioprinting for Cardiovascular Regeneration and Pharmacology
,”
Adv. Drug Delivery Rev.
,
132
, pp.
252
269
.10.1016/j.addr.2018.07.014
3.
Hann
,
S. Y.
,
Cui
,
H.
,
Esworthy
,
T.
,
Miao
,
S.
,
Zhou
,
X.
,
Lee
,
S.
,
Fisher
,
J. P.
, and
Zhang
,
L. G.
,
2019
, “
Recent Advances in 3D Printing: Vascular Network for Tissue and Organ Regeneration
,”
Transl. Res.
,
211
, pp.
46
63
.10.1016/j.trsl.2019.04.002
4.
Yang
,
G.
,
Mahadik
,
B.
,
Choi
,
J. Y.
, and
Fisher
,
J. P.
,
2020
, “
Vascularization in Tissue Engineering: Fundamentals and State-of-Art
,”
Prog. Biomed. Eng.
,
2
(
1
), p.
012002
.10.1088/2516-1091/ab5637
5.
Liu
,
C.
,
Wang
,
Z.
,
Wei
,
X.
,
Chen
,
B.
, and
Luo
,
Y.
,
2021
, “
3D Printed Hydrogel/PCL Core/Shell Fiber Scaffolds With NIR-Triggered Drug Release for Cancer Therapy and Wound Healing
,”
Acta Biomater.
,
131
, pp.
314
325
.10.1016/j.actbio.2021.07.011
6.
Yin
,
Y.
,
He
,
X.-T.
,
Wang
,
J.
,
Wu
,
R.-X.
,
Xu
,
X.-Y.
,
Hong
,
Y.-L.
,
Tian
,
B.-M.
, and
Chen
,
F.-M.
,
2020
, “
Pore Size-Mediated Macrophage M1-to-M2 Transition Influences New Vessel Formation Within the Compartment of a Scaffold
,”
Appl. Mater. Today
,
18
, p.
100466
.10.1016/j.apmt.2019.100466
7.
Reinwald
,
Y.
,
Johal
,
R. K.
,
Ghaemmaghami
,
A. M.
,
Rose
,
F. R. A. J.
,
Howdle
,
S. M.
, and
Shakesheff
,
K. M.
,
2014
, “
Interconnectivity and Permeability of Supercritical Fluid-Foamed Scaffolds and the Effect of Their Structural Properties on Cell Distribution
,”
Polymer
,
55
(
1
), pp.
435
444
.10.1016/j.polymer.2013.09.041
8.
Jia
,
G.
,
Huang
,
H.
,
Niu
,
J.
,
Chen
,
C.
,
Weng
,
J.
,
Yu
,
F.
,
Wang
,
D.
,
Kang
,
B.
,
Wang
,
T.
,
Yuan
,
G.
, and
Zeng
,
H.
,
2021
, “
Exploring the Interconnectivity of Biomimetic Hierarchical Porous Mg Scaffolds for Bone Tissue Engineering: Effects of Pore Size Distribution on Mechanical Properties, Degradation Behavior and Cell Migration Ability
,”
J. Magnesium Alloys
,
9
(
6
), pp.
1954
1966
.10.1016/j.jma.2021.02.001
9.
Kang
,
Y.
, and
Chang
,
J.
,
2018
, “
Channels in a Porous Scaffold: A New Player for Vascularization
,”
Regener. Med.
,
13
(
6
), pp.
705
715
.10.2217/rme-2018-0022
10.
Tang
,
F.
,
Manz
,
X. D.
,
Bongers
,
A.
,
Odell
,
R. A.
,
Joukhdar
,
H.
,
Whitelock
,
J. M.
,
Lord
,
M. S.
, and
Rnjak-Kovacina
,
J.
,
2020
, “
Microchannels Are an Architectural Cue That Promotes Integration and Vascularization of Silk Biomaterials In Vivo
,”
ACS Biomater. Sci. Eng.
,
6
(
3
), pp.
1476
1486
.10.1021/acsbiomaterials.9b01624
11.
Zhang
,
W.
,
Wray
,
L. S.
,
Rnjak-Kovacina
,
J.
,
Xu
,
L.
,
Zou
,
D.
,
Wang
,
S.
,
Zhang
,
M.
,
Dong
,
J.
,
Li
,
G.
,
Kaplan
,
D. L.
, and
Jiang
,
X.
,
2015
, “
Vascularization of Hollow Channel-Modified Porous Silk Scaffolds With Endothelial Cells for Tissue Regeneration
,”
Biomaterials
,
56
, pp.
68
77
.10.1016/j.biomaterials.2015.03.053
12.
Shafiee
,
A.
, and
Atala
,
A.
,
2017
, “
Tissue Engineering: Toward a New Era of Medicine
,”
Annu. Rev. Med.
,
68
(
1
), pp.
29
40
.10.1146/annurev-med-102715-092331
13.
Naveau
,
A.
,
Smirani
,
R.
,
Remy
,
M.
,
Pomar
,
P.
, and
Destruhaut
,
F.
,
2019
, “
Cyborgology and Bioprinting: The Biotechnological Future of Maxillofacial Rehabilitation
,”
Int. J. Maxillofac. Prosthet.
,
2
(
1
), pp.
20
26
.10.26629/ijmp.2019.05
14.
You
,
S.
,
Xiang
,
Y.
,
Hwang
,
H. H.
,
Berry
,
D. B.
,
Kiratitanaporn
,
W.
,
Guan
,
J.
,
Yao
,
E.
,
Tang
,
M.
,
Zhong
,
Z.
,
Ma
,
X.
,
Wangpraseurt
,
D.
,
Sun
,
Y.
,
Lu
,
T.
, and
Chen
,
S.
,
2023
, “
High Cell Density and High-Resolution 3D Bioprinting for Fabricating Vascularized Tissues
,”
Sci. Adv.
,
9
(
8
), p.
eade7923
.10.1126/sciadv.ade7923
15.
Kolesky
,
D. B.
,
Homan
,
K. A.
,
Skylar-Scott
,
M. A.
, and
Lewis
,
J. A.
,
2016
, “
Three-Dimensional Bioprinting of Thick Vascularized Tissues
,”
Proc. Natl. Acad. Sci. U. S. A.
,
113
(
12
), pp.
3179
3184
.10.1073/pnas.1521342113
16.
Xia
,
P.
, and
Luo
,
Y.
,
2022
, “
Vascularization in Tissue Engineering: The Architecture Cues of Pores in Scaffolds
,”
J. Biomed. Mater. Res., Part B
,
110
(
5
), pp.
1206
1214
.10.1002/jbm.b.34979
17.
Tan
,
B.
,
Gan
,
S.
,
Wang
,
X.
,
Liu
,
W.
, and
Li
,
X.
,
2021
, “
Applications of 3D Bioprinting in Tissue Engineering: Advantages, Deficiencies, Improvements, and Future Perspectives
,”
J. Mater. Chem. B
,
9
(
27
), pp.
5385
5413
.10.1039/D1TB00172H
18.
Saini
,
G.
,
Segaran
,
N.
,
Mayer
,
J.
,
Saini
,
A.
,
Albadawi
,
H.
, and
Oklu
,
R.
,
2021
, “
Applications of 3D Bioprinting in Tissue Engineering and Regenerative Medicine
,”
JCM
,
10
(
21
), p.
4966
.10.3390/jcm10214966
19.
Raees
,
S.
,
Ullah
,
F.
,
Javed
,
F.
,
Akil
,
H. M.
,
Jadoon Khan
,
M.
,
Safdar
,
M.
,
Din
,
I. U.
,
Alotaibi
,
M. A.
,
Alharthi
,
A. I.
,
Bakht
,
M. A.
,
Ahmad
,
A.
, and
Nassar
,
A. A.
,
2023
, “
Classification, Processing, and Applications of Bioink and 3D Bioprinting: A Detailed Review
,”
Int. J. Biol. Macromol.
,
232
, p.
123476
.10.1016/j.ijbiomac.2023.123476
20.
Lee
,
A.
,
Hudson
,
A. R.
,
Shiwarski
,
D. J.
,
Tashman
,
J. W.
,
Hinton
,
T. J.
,
Yerneni
,
S.
,
Bliley
,
J. M.
,
Campbell
,
P. G.
, and
Feinberg
,
A. W.
,
2019
, “
3D Bioprinting of Collagen to Rebuild Components of the Human Heart
,”
Science
,
365
(
6452
), pp.
482
487
.10.1126/science.aav9051
21.
Li
,
S.
,
Li
,
H.
,
Shang
,
X.
,
He
,
J.
, and
Hu
,
Y.
,
2023
, “
Recent Advances in 3D Printing Sacrificial Templates for Fabricating Engineered Vasculature
,”
MedComm: Biomater. Appl.
,
2
(
3
), p.
e46
.10.1002/mba2.46
22.
Zhou
,
T.
,
NajafiKhoshnoo
,
S.
,
Esfandyarpour
,
R.
, and
Kulinsky
,
L.
,
2023
, “
Dissolvable Calcium Alginate Microfibers Produced Via Immersed Microfluidic Spinning
,”
Micromachines
,
14
(
2
), p.
318
.10.3390/mi14020318
You do not currently have access to this content.