Coaxial extrusion-based bioprinting (EBB) is an emerging technology that enables the fabrication of biomimetic tissues with precise structural and biological complexities. This three-dimensional bioprinting technique utilizes specialized concentric nozzles to facilitate the simultaneous extrusion of distinct biomaterials, enabling the fabrication of layered constructs that closely resemble native tissues. Unlike traditional extrusion-based methods, coaxial printing allows for independent control over core and shell materials. This enables multimaterial integration, and tailored microenvironments that conventional extrusion methods cannot achieve. Recent technical innovations in coaxial EBB also include improved nozzle designs and bioink formulations, which have contributed to enhanced functional mimicry of native tissues and mechanical integrity of printed constructs. Coaxial EBB has demonstrated potential in spinal cord injury repair, perfusable small-diameter vessel engineering, accurate tumor microenvironment replication for oncology research, and complex organoid systems for personalized medicine. Despite these advancements, persistent challenges in coaxial EBB include maintaining cell viability under shear stress, optimizing bioink rheology, preventing nozzle clogging, and managing regulatory considerations. Future research directions involve the development of predictive computational models and the incorporation of innovative biomaterials for dynamic functionality. Addressing these challenges would allow the full therapeutic and clinical potential of coaxial bioprinting in regenerative medicine to be achieved. This review discusses and summarizes these advancements and limitations in coaxial EBB over the last decade, with an emphasis on applications in regenerative medicine.
Impact Statement
Coaxial extrusion-based bioprinting (EBB) is an innovative technology that is transforming regenerative medicine. Its design allows for simultaneous coextrusion of two or more bioinks to create three-dimensional structures that promote tissue-like function. It has been applied in nerve conduit fabrication, tumor modeling, and organoid development. This review highlights recent technological and biological advancements of coaxial EBB and challenges like maintaining cellular viability or optimizing bioink extrusion properties. Future innovations discussed also include exploring dynamic biomaterials to achieve coaxial EBB’s transformative potential to inform future translational preclinical and clinical work.
NgWL, VyasC, HuangB, et al.Advanced bioprinting strategies for fabrication of biomimetic tissues and organs. Int J Extrem Manuf, 2025; 7(6):62006.
2.
BertassoniLE. Bioprinting of complex multicellular organs with advanced functionality—Recent progress and challenges ahead. Advanced Materials, 2022; 34(3):2101321.
3.
MohanTS, DattaP, NesaeiS, et al.3D coaxial bioprinting: Process mechanisms, bioinks and applications. Prog Biomed Eng (Bristol), 2022; 4(2):22003; doi: 10.1088/2516-1091/ac631c
4.
KlebeRJ. Cytoscribing: A method for micropositioning cells and the construction of two- and three-dimensional synthetic tissues. Exp Cell Res, 1988; 179(2):362–373; doi: 10.1016/0014-4827(88)90275-3
5.
DeyM, OzbolatIT. 3D bioprinting of cells, tissues, and organs. Sci Rep, 2020; 10(1):14023; doi: 10.1038/s41598-020-70086-y
6.
ZhuW, MaX, GouM, et al.3D printing of functional biomaterials for tissue engineering. Curr Opin Biotechnol, 2016; 40:103–112; doi: 10.1016/j.copbio.2016.03.014
7.
ChokshiS, GangatirkarR, KandiA, et al.Medical 3D printing using material jetting: Technology overview, medical applications, and challenges. Bioengineering (Basel), 2025; 12(3):249; doi: 10.3390/bioengineering12030249
8.
ChengC, WilliamsonEJ, ChiuGT, et al.Engineering biomaterials by inkjet printing of hydrogels with functional particulates. Med X, 2024; 2(1):9; doi: 10.1007/s44258-024-00024-4
9.
OzbolatIT. 3D Bioprinting Fundamentals: Principles and Applications. Elsevier; 2017.
10.
PapaioannouTG, ManolesouD, DimakakosE, et al.3D bioprinting methods and techniques: Applications on artificial blood vessel fabrication. Acta Cardiol Sin, 2019; 35(3):284–289; doi: 10.6515/acs.201905_35(3).20181115a
11.
SivalingamS, BhuvaneswariV, RajeshkumarL, et al.Additive manufacturing of metal-infilled polylactic acid-based sustainable biocomposites-A review of methods, properties and applications abetted with patent landscape analysis. Polymers (Basel), 2025; 17(11):1565; doi: 10.3390/polym17111565
12.
HoYH, LiaoY, LiaoL, et al.Advances of cell printing technology in organoid engineering. Tissue Eng Part B Rev, 2025; doi: 10.1089/ten.teb.2025.0048
13.
CongB, ZhangH. Innovative 3D printing technologies and advanced materials revolutionizing orthopedic surgery: Current applications and future directions. Front Bioeng Biotechnol, 2025; 13:1542179; doi: 10.3389/fbioe.2025.1542179
14.
GaoQ, HeY, FuJZ, et al.Coaxial nozzle-assisted 3D bioprinting with built-in microchannels for nutrients delivery. Biomaterials, 2015; 61:203–215; doi: 10.1016/j.biomaterials.2015.05.031
15.
CostantiniM, ColosiC, ŚwięszkowskiW, et al.Co-axial wet-spinning in 3D bioprinting: State of the art and future perspective of microfluidic integration. Biofabrication, 2018; 11(1):12001; doi: 10.1088/1758-5090/aae605
16.
VijayavenkataramanS, YanWC, LuWF, et al.3D bioprinting of tissues and organs for regenerative medicine. Adv Drug Deliv Rev, 2018; 132:296–332; doi: 10.1016/j.addr.2018.07.004
17.
MurphySV, AtalaA. 3D bioprinting of tissues and organs. Nat Biotechnol, 2014; 32(8):773–785; doi: 10.1038/nbt.2958
18.
SunJ, GongY, XuM, et al.Coaxial 3D bioprinting process research and performance tests on vascular scaffolds. Micromachines (Basel), 2024; 15(4):463.
19.
SunJ, GongY, HeY, et al.Process optimization for coaxial extrusion-based bioprinting: A comprehensive analysis of material behavior, structural precision, and cell viability. Addit Manuf, 2025; 100:104682.
20.
LiX, ZhouD, JinZ, et al.A coaxially extruded heterogeneous core-shell fiber with Schwann cells and neural stem cells. Regen Biomater, 2020; 7(2):131–139; doi: 10.1093/rb/rbz037
21.
ShaoL, GaoQ, XieC, et al.Bioprinting of cell-laden microfiber: Can it become a standard product? Adv Healthc Mater, 2019; 8(9):e1900014; doi: 10.1002/adhm.201900014
22.
ZhouX, NowickiM, SunH, et al.3D bioprinting-tunable small-diameter blood vessels with biomimetic biphasic cell layers. ACS Appl Mater Interfaces, 2020; 12(41):45904–45915; doi: 10.1021/acsami.0c14871
23.
ZhangJ, LiX, GuoL, et al.3D hydrogel microfibers promote the differentiation of encapsulated neural stem cells and facilitate neuron protection and axon regrowth after complete transactional spinal cord injury. Biofabrication, 2024; 16(3); doi: 10.1088/1758-5090/ad39a7
24.
WangH, LiuZ, FangY, et al.Spatiotemporal release of non-nucleotide STING agonist and AKT inhibitor from implantable 3D-printed scaffold for amplified cancer immunotherapy. Biomaterials, 2024; 311:122645; doi: 10.1016/j.biomaterials.2024.122645
25.
SilvaC, Cortés-RodriguezCJ, HazurJ, et al.Rational design of a triple-layered coaxial extruder system: In silico and in vitro evaluations directed toward optimizing cell viability. Int J Bioprint, 2020; 6(4):282; doi: 10.18063/ijb.v6i4.282
26.
LiY, ChengS, WenH, et al.Coaxial 3D printing of hierarchical structured hydrogel scaffolds for on-demand repair of spinal cord injury. Acta Biomater, 2023; 168:400–415; doi: 10.1016/j.actbio.2023.07.020
27.
WangZ, HuangC, LiuH, et al.Two-step method fabricating a 3D nerve cell model with brain-like mechanical properties and tunable porosity vascular structures via coaxial printing. Colloids Surf B Biointerfaces, 2023; 224:113202; doi: 10.1016/j.colsurfb.2023.113202
28.
ZhuJ, MaH, DuJ, et al.A coaxial 3D bioprinted hybrid vascular scaffold based on decellularized extracellular matrix/nano clay/sodium alginate bioink. Int J Biol Macromol, 2025; 290:139056; doi: 10.1016/j.ijbiomac.2024.139056
29.
HuQ, ShenZ, ZhangH, et al.Designed and fabrication of triple-layered vascular scaffold with microchannels. J Biomater Sci Polym Ed, 2021; 32(6):714–734; doi: 10.1080/09205063.2020.1864083
30.
ZengZ, HuC, LiangQ, et al.Coaxial-printed small-diameter polyelectrolyte-based tubes with an electrostatic self-assembly of heparin and YIGSR peptide for antithrombogenicity and endothelialization. Bioact Mater, 2021; 6(6):1628–1638; doi: 10.1016/j.bioactmat.2020.10.028
31.
MillikSC, DostieAM, KarisDG, et al.3D printed coaxial nozzles for the extrusion of hydrogel tubes toward modeling vascular endothelium. Biofabrication, 2019; 11(4):45009; doi: 10.1088/1758-5090/ab2b4d
32.
ShaoL, GaoQ, ZhaoH, et al.Fiber-based mini tissue with morphology-controllable GelMA microfibers. Small, 2018; 14(44):e1802187; doi: 10.1002/smll.201802187
33.
GaoQ, LiuZ, LinZ, et al.3D bioprinting of vessel-like structures with multilevel fluidic channels. ACS Biomater Sci Eng, 2017; 3(3):399–408; doi: 10.1021/acsbiomaterials.6b00643
34.
WonJY, KimJ, GaoG, et al.3D printing of drug-loaded multi-shell rods for local delivery of bevacizumab and dexamethasone: A synergetic therapy for retinal vascular diseases. Acta Biomater, 2020; 116:174–185; doi: 10.1016/j.actbio.2020.09.015
35.
AttallaR, LingC, SelvaganapathyP. Fabrication and characterization of gels with integrated channels using 3D printing with microfluidic nozzle for tissue engineering applications. Biomed Microdevices, 2016; 18(1):17; doi: 10.1007/s10544-016-0042-6
36.
JiaW, Gungor-OzkerimPS, ZhangYS, et al.Direct 3D bioprinting of perfusable vascular constructs using a blend bioink. Biomaterials, 2016; 106:58–68; doi: 10.1016/j.biomaterials.2016.07.038
37.
GuimarãesCF, LiuS, WangJ, et al.Co-axial hydrogel spinning for facile biofabrication of prostate cancer-like 3D models. Biofabrication, 2024; 16(2); doi: 10.1088/1758-5090/ad2535
38.
DaiX, ShaoY, TianX, et al.Fusion between glioma stem cells and mesenchymal stem cells promotes malignant progression in 3D-bioprinted models. ACS Appl Mater Interfaces, 2022; 14(31):35344–35356; doi: 10.1021/acsami.2c06658
39.
WangX, LiX, ZhangY, et al.Coaxially bioprinted cell-laden tubular-like structure for studying glioma angiogenesis. Front Bioeng Biotechnol, 2021; 9:761861; doi: 10.3389/fbioe.2021.761861
40.
WangX, LiX, DaiX, et al.Coaxial extrusion bioprinted shell-core hydrogel microfibers mimic glioma microenvironment and enhance the drug resistance of cancer cells. Colloids Surf B Biointerfaces, 2018; 171:291–299; doi: 10.1016/j.colsurfb.2018.07.042
41.
DaiX, LiuL, OuyangJ, et al.Coaxial 3D bioprinting of self-assembled multicellular heterogeneous tumor fibers. Sci Rep, 2017; 7(1):1457; doi: 10.1038/s41598-017-01581-y
42.
RobinsonM, BedfordE, WitherspoonL, et al.Using clinically derived human tissue to 3-dimensionally bioprint personalized testicular tubules for in vitro culturing: First report. F S Sci, 2022; 3(2):130–139; doi: 10.1016/j.xfss.2022.02.004
43.
LianL, ZhouC, TangG, et al.Uniaxial and coaxial vertical embedded extrusion bioprinting. Adv Healthc Mater, 2022; 11(9):e2102411; doi: 10.1002/adhm.202102411
44.
PiQ, MaharjanS, YanX, et al.Digitally tunable microfluidic bioprinting of multilayered cannular tissues. Adv Mater, 2018; 30(43):e1706913; doi: 10.1002/adma.201706913
45.
AttallaR, PuerstenE, JainN, et al.3D bioprinting of heterogeneous bi- and tri-layered hollow channels within gel scaffolds using scalable multi-axial microfluidic extrusion nozzle. Biofabrication, 2018; 11(1):15012; doi: 10.1088/1758-5090/aaf7c7
46.
LiS, LiuY, LiY, et al.A novel method for fabricating engineered structures with branched micro-channel using hollow hydrogel fibers. Biomicrofluidics, 2016; 10(6):64104; doi: 10.1063/1.4967456
47.
ZhangJ, SuttapreyasriS, LeethanakulC, et al.Triaxial bioprinting large-size vascularized constructs with nutrient channels. Biomed Mater, 2023; 18(5); doi: 10.1088/1748-605X/acf25a
48.
ZhangJ, SuttapreyasriS, LeethanakulC, et al.Fabrication of vascularized tissue-engineered bone models using triaxial bioprinting. J Biomed Mater Res A, 2024; 112(7):1093–1106; doi: 10.1002/jbm.a.37694
49.
GhahriT, SalehiZ, AghajanpourS, et al.Development of osteon-like scaffold-cell construct by quadruple coaxial extrusion-based 3D bioprinting of nanocomposite hydrogel. Biomater Adv, 2023; 145:213254; doi: 10.1016/j.bioadv.2022.213254
50.
AlhattabDM, IsaioglouI, AlshehriS, et al.Fabrication of a three-dimensional bone marrow niche-like acute myeloid leukemia disease model by an automated and controlled process using a robotic multicellular bioprinting system. Biomater Res, 2023; 27(1):111; doi: 10.1186/s40824-023-00457-9
51.
JingL, CiH, ZhangZ, et al.The sculpting tool in bioprinting: Research and application progress of sacrificial inks. Front Bioeng Biotechnol, 2025; 13:1486459; doi: 10.3389/fbioe.2025.1486459
52.
HongS, KimJS, JungB, et al.Coaxial bioprinting of cell-laden vascular constructs using a gelatin-tyramine bioink. Biomater Sci, 2019; 7(11):4578–4587; doi: 10.1039/c8bm00618k
53.
DuanN, GengX, YeL, et al.A vascular tissue engineering scaffold with core-shell structured nano-fibers formed by coaxial electrospinning and its biocompatibility evaluation. Biomed Mater, 2016; 11(3):35007; doi: 10.1088/1748-6041/11/3/035007
WuH, GuoC, WangC, et al.Single-cell RNA sequencing reveals tumor heterogeneity, microenvironment, and drug-resistance mechanisms of recurrent glioblastoma. Cancer Sci, 2023; 114(6):2609–2621; doi: 10.1111/cas.15773
56.
TufailM. Unlocking the potential of the tumor microenvironment for cancer therapy. Pathol Res Pract, 2023; 251:154846; doi: 10.1016/j.prp.2023.154846
57.
CribaroGP, Saavedra-LópezE, RomarateL, et al.Three-dimensional vascular microenvironment landscape in human glioblastoma. Acta Neuropathol Commun, 2021; 9(1):24; doi: 10.1186/s40478-020-01115-0
58.
YangS, HuH, KungH, et al.Organoids: The current status and biomedical applications. MedComm (2020), 2023; 4(3):e274; doi: 10.1002/mco2.274
59.
KimJ, KooBK, KnoblichJA. Human organoids: Model systems for human biology and medicine. Nat Rev Mol Cell Biol, 2020; 21(10):571–584; doi: 10.1038/s41580-020-0259-3
60.
ChibaK, EnatsuN, FujisawaM. Management of non-obstructive azoospermia. Reprod Med Biol, 2016; 15(3):165–173; doi: 10.1007/s12522-016-0234-z
61.
Vunjak-NovakovicG, TandonN, GodierA, et al.Challenges in cardiac tissue engineering. Tissue Eng Part B Rev, 2010; 16(2):169–187; doi: 10.1089/ten.TEB.2009.0352
62.
KaullyT, Kaufman-FrancisK, LesmanA, et al.Vascularization–The conduit to viable engineered tissues. Tissue Eng Part B Rev, 2009; 15(2):159–169; doi: 10.1089/ten.teb.2008.0193
63.
BradyEL, PradoO, JohanssonF, et al.Engineered tissue vascularization and engraftment depends on host model. Sci Rep, 2023; 13(1):1973; doi: 10.1038/s41598-022-23895-2
64.
BanigoAT, NautaL, ZoetebierB, et al.Hydrogel-based bioinks for coaxial and triaxial bioprinting: A review of material properties, printing techniques, and applications. Polymers (Basel), 2025; 17(7):917; doi: 10.3390/polym17070917
65.
JiangH, LiX, ChenT, et al.Bioprinted vascular tissue: Assessing functions from cellular, tissue to organ levels. Mater Today Bio, 2023; 23:100846; doi: 10.1016/j.mtbio.2023.100846
66.
ZhangJ, WehrleE, RubertM, et al.3D bioprinting of human tissues: Biofabrication, bioinks, and bioreactors. Int J Mol Sci, 2021; 22(8):3971; doi: 10.3390/ijms22083971
67.
MathurV, AgarwalP, KasturiM, et al.Innovative bioinks for 3D bioprinting: Exploring technological potential and regulatory challenges. J Tissue Eng, 2025; 16:20417314241308022; doi: 10.1177/20417314241308022
68.
PuschK, HintonTJ, FeinbergAW. Large volume syringe pump extruder for desktop 3D printers. HardwareX, 2018; 3:49–61.
69.
JergitschM, SoiunovR, SelingerF, et al.Fabrication and validation of an affordable DIY coaxial 3D extrusion bioprinter. Sci Rep, 2025; 15(1):22978.
70.
Garciamendez-MijaresCE, AgrawalP, García MartínezG, et al.State-of-art affordable bioprinters: A guide for the DiY community. Applied Physics Reviews, 2021; 8(3).
71.
KahlM, GertigM, HoyerP, et al.Ultra-low-cost 3D bioprinting: Modification and application of an off-the-shelf desktop 3D-printer for biofabrication. Front Bioeng Biotechnol, 2019; 7:184.
72.
LeeJ, KimKE, BangS, et al.A desktop multi-material 3D bio-printing system with open-source hardware and software. Int J Precis Eng Manuf, 2017; 18(4):605–612.
73.
BhattacharjeeT, ZehnderSM, RoweKG, et al.Writing in the granular gel medium. Sci Adv, 2015; 1(8):e1500655.
74.
Van Den BulckeAI, BogdanovB, De RoozeN, et al.Structural and rheological properties of methacrylamide modified gelatin hydrogels. Biomacromolecules, 2000; 1(1):31–38; doi: 10.1021/bm990017d
75.
OuyangL, YaoR, ZhaoY, et al.Effect of bioink properties on printability and cell viability for 3D bioplotting of embryonic stem cells. Biofabrication, 2016; 8(3):35020; doi: 10.1088/1758-5090/8/3/035020
76.
ZhaoY, LiY, MaoS, et al.The influence of printing parameters on cell survival rate and printability in microextrusion-based 3D cell printing technology. Biofabrication, 2015; 7(4):45002; doi: 10.1088/1758-5090/7/4/045002
77.
GuZ, FuJ, LinH, et al.Development of 3D bioprinting: From printing methods to biomedical applications. Asian J Pharm Sci, 2020; 15(5):529–557; doi: 10.1016/j.ajps.2019.11.003
78.
NairK, GandhiM, KhalilS, et al.Characterization of cell viability during bioprinting processes. Biotechnol J, 2009; 4(8):1168–1177; doi: 10.1002/biot.200900004
79.
KimSH, YeonYK, LeeJM, et al.Precisely printable and biocompatible silk fibroin bioink for digital light processing 3D printing. Nat Commun, 2018; 9(1):1620; doi: 10.1038/s41467-018-03759-y
80.
XuC, LeeW, DaiG, et al.Highly elastic biodegradable single-network hydrogel for cell printing. ACS Appl Mater Interfaces, 2018; 10(12):9969–9979; doi: 10.1021/acsami.8b01294
81.
WangJ, KongL, GafurA, et al.Photooxidation crosslinking to recover residual stress in decellularized blood vessel. Regen Biomater, 2021; 8(2):rbaa058; doi: 10.1093/rb/rbaa058
82.
ZhaiX, MaY, HouC, et al.3D-Printed high strength bioactive supramolecular polymer/clay nanocomposite hydrogel scaffold for bone regeneration. ACS Biomater Sci Eng, 2017; 3(6):1109–1118; doi: 10.1021/acsbiomaterials.7b00224
83.
LeppiniemiJ, LahtinenP, PaajanenA, et al.3D-printable bioactivated nanocellulose-alginate hydrogels. ACS Appl Mater Interfaces, 2017; 9(26):21959–21970; doi: 10.1021/acsami.7b02756
84.
CarracciuoloL, D’AmoraU. Mathematical tools for simulation of 3D bioprinting processes on high-performance computing resources: The state of the art. Applied Sciences, 2024; 14(14):6110.
85.
SuntornnondR, TanEYS, AnJ, et al.A mathematical model on the resolution of extrusion bioprinting for the development of new bioinks. Materials (Basel), 2016; 9(9):756.
86.
TemirelM, DabbaghSR, TasogluS. Shape fidelity evaluation of alginate-based hydrogels through extrusion-based bioprinting. J Funct Biomater, 2022; 13(4):225; doi: 10.3390/jfb13040225
87.
CuiC, KimDO, PackMY, et al.4D printing of self-folding and cell-encapsulating 3D microstructures as scaffolds for tissue-engineering applications. Biofabrication, 2020; 12(4):45018; doi: 10.1088/1758-5090/aba502
88.
Rahmani DabbaghS, OzcanO, TasogluS. Machine learning-enabled optimization of extrusion-based 3D printing. Methods, 2022; 206:27–40; doi: 10.1016/j.ymeth.2022.08.002
89.
KalogeropoulouM, Díaz-PaynoPJ, MirzaaliMJ, et al.4D printed shape-shifting biomaterials for tissue engineering and regenerative medicine applications. Biofabrication, 2024; 16(2); doi: 10.1088/1758-5090/ad1e6f
90.
ZarekM, MansourN, ShapiraS, et al.4D printing of shape memory-based personalized endoluminal medical devices. Macromol Rapid Commun, 2017; 38(2); doi: 10.1002/marc.201600628
91.
KuangX, ChenK, DunnCK, et al.3D printing of highly stretchable, shape-memory, and self-healing elastomer toward novel 4D printing. ACS Appl Mater Interfaces, 2018; 10(8):7381–7388; doi: 10.1021/acsami.7b18265
92.
ZhangC, CaiD, LiaoP, et al.4D Printing of shape-memory polymeric scaffolds for adaptive biomedical implantation. Acta Biomater, 2021; 122:101–110; doi: 10.1016/j.actbio.2020.12.042
93.
KammonaO, TsanaktsidouE, KiparissidesC. Recent developments in 3D-(bio) printed hydrogels as wound dressings. Gels, 2024; 10(2):147; doi: 10.3390/gels10020147
94.
UzelSGM, WeeksRD, ErikssonM, et al.Multimaterial multinozzle adaptive 3D printing of soft materials. Adv Materials Technologies, 2022; 7(8):2101710; doi: 10.1002/admt.202101710
95.
Trigo TorresRS, KulinskyL, KheradvarA. Characterization of the coating layers deposited onto curved surfaces using a novel multi-nozzle extrusion printer. Micromachines (Basel), 2025; 16(5):505; doi: 10.3390/mi16050505
96.
MladenovskaT, ChoongPF, WallaceGG, et al.The regulatory challenge of 3D bioprinting. Regen Med, 2023; 18(8):659–674; doi: 10.2217/rme-2022-0194
97.
LiP, AlexF, MedcalfN. 3D bioprinting in a 2D regulatory landscape: Gaps, uncertainties, and problems. Law Innov Technol, 2020; 12(1):1–29; doi: 10.1080/17579961.2020.1727054
