1. What bioprinting is (the short version)

Bioprinting is a technology that places material containing cells at set positions in three dimensions, following design data. In a 2014 review [Source 22], Murphy et al. said that 3D bioprinting means printing biocompatible materials, cells and supporting components into complex, functional, living three-dimensional tissues, and that technical challenges around the choice of materials, cell types, growth and differentiation factors, and the sensitivities of living cells add a complexity that non-biological 3D printing does not haveSourced.

• What is printed: a formulation that contains cells and can be handled in an automated fabrication process is called a "bioink". One without cells is a "biomaterial ink" (the definition of Groll et al.) [Source 1]Sourced. This definition and the basics of the materials were covered in our explainer on hydrogels
• How it is printed: the review by Xu et al. divides the methods into four: inkjet, extrusion, laser-assisted and stereolithography [Source 3]Sourced
• What is hard: cells experience various stresses during printing, and the stronger and longer the stress, the lower the viability is said to be. And thick tissue dies from necrosis without blood vessels insideSourced

2. Four methods — extrusion, inkjet, light-based and laser

The review by Xu et al. sorts, for each method, the main stress on cells, the suitable viscosity of the material and a guide to reported viability. Moroni et al. point out that terminology in the field of biofabrication is inconsistent, and give a guide that sets out how techniques and terms relate [Source 2]Sourced.

Extrusion — the most versatile, and the one that applies the most force

In 2016, Ozbolat et al. summarised extrusion-based bioprinting (EBB) [Source 4] as versatile enough to print a wide range of things, including cells, tissues, tissue constructs, organ modules and microfluidic devices, yet facing obstacles to organ fabrication, limits on the resolution of printed features, challenges to practical use, the development of new bioinks, and regulatory concerns on the way to commercialisationSourced. They list as forms of bioink tissue spheroids, tissue strands, cell pellets, decellularized matrix components, microcarriers and cell-laden hydrogelsSourced.

Inkjet — low viscosity and tiny droplets

In 2010, Cui et al. [Source 7] examined Chinese hamster ovary (CHO) cells printed with a thermal inkjet and reported viability of 89% after printing and 3.5% apoptosis, with transient pores forming in the cell membrane that were repaired within 2 hours. The optimum cell concentration was about 8 million cells/mLSourced. The review also says that cell damage grows when the nozzle temperature exceeds 37 °CSourced.

Stereolithography and laser — methods without a nozzle

In stereolithography (DLP and the like), almost no nozzle shear is applied, and the main damage is radiation stress from the light source and the cytotoxicity of the photoinitiatorSourced. The review's table lists viability of 85% to 91.5% for examples using GelMA and a photosensitizerSourced. Laser-assisted printing (LIFT) has no nozzle and so faces fewer viscosity limits, and there are examples with reported viability above 90%Sourced. Examples of making structures that include blood vessels by stereolithography are covered in chapter 7.

3. Bioink materials — collagen, alginate, GelMA and decellularized matrix

The basic properties of collagen, alginate and GelMA (origin, how they gel, elastic modulus, cell adhesion) were covered in our explainer on hydrogels. Here we sort out the points that bear on printing.

Collagen follows Lee et al. [Source 14], alginate Ouyang et al. [Source 8], dECM Pati et al. [Source 9], and the load of GelMA on cells the review by Xu et al. [Source 3]. The "what becomes a problem" column is this article's arrangement based on what the literature states.

Reading dECM bioink from the materials side

4. A materials engineer's view (1): three time scales — during printing, after landing and in culture

5. Cell viability and shear

The review by Xu et al. sorts out that cell viability is determined mainly by the size and the duration of the stress received: the higher the stress and the longer the time, the lower the viability. In nozzle-based methods cells mainly receive shear stress on ejection, and in light-based methods they receive thermal and radiation stressSourced. The review also cites the view that if shear stretches the cell membrane by more than 5%, the membrane can no longer hold its shape, ruptures and the cell diesSourced.

• Effect of pressure (Nair et al., 2009) [Source 5]: varying pressure and nozzle diameter and examining cell damage, they reported that dispensing pressure affects viability more than nozzle diameter does, and that in structures printed at 40 psi the proportion of living cells was 38.75% lower than at 5 psiSourced
• Relation between shear stress and viability (Ouyang et al., 2016) [Source 8]: they reported an exponential relationship between embryonic stem cell viability and the shear stress induced, and that viability was higher at higher printing temperature and lower gelatin concentrationSourced
• Controlling shear (Blaeser et al., 2016) [Source 21]: using a microvalve-based device, they controlled the shear stress in the nozzle with a fluid-dynamics model and examined how the level of shear stress affects cell survival and proliferative capacitySourced
• Relation to injection (Aguado et al., 2012) [Source 6]: both experiment and theory suggest that the stretching flow at the needle inlet is the main cause of acute cell deathSourced

A caution is needed here. The viability figure changes with whether it is measured right after printing or several days later, with the stain used, and with the cells. Also, being "alive" is not the same as "functioning". The review by Xu et al. says that, besides viability, keeping the pluripotency and differentiation capacity of stem cells is a precondition for the function of engineered tissueSourced.

6. Our calculation: what order of magnitude is the shear stress in the nozzle?

Shear stress can be estimated roughly from the conditions of the material and the equipment. To get the order of magnitude, we use two relations.

What can be read from this is as follows (commentary from this article).

• The low-shear condition of Pati et al. (about 50 Pa) is two orders of magnitude below the review's "under 5 kPa" band. The design is to extrude cold at a low shear rate and support the shape with a frame until it sets
• Even a material of about 1 Pa·s can reach stresses of several kPa with a fine nozzle and fast printing. Narrowing the nozzle raises resolution, but the stress climbs steeply (it scales with the third power of the radius)
• The ways to lower stress come to four: lower the viscosity (temperature, concentration), strengthen shear thinning, widen the nozzle, or print more slowly. The first two are material design; the last two are a trade-off of equipment against resolution

7. How to add a vascular network

Thick tissue needs channels that carry oxygen and nutrients to its interior. In 2012, Miller et al. stated that without a perfusable vascular network, a three-dimensional tissue packed with cells soon develops a necrotic coreSourced. We calculated that the limit of oxygen diffusion is of the order of a few hundred µm in our explainer on organoids and spheroids. In bioprinting, making channels at the same time as the shape of the tissue becomes a central design problem.

Four ways to make perfusable channels

The left side of each image shows fabrication; the right side shows a cutaway of the result. Blue represents culture medium flowing through the open channel.

1. Embed and remove a sacrificial template (Miller et al.)

1. Print sugar template
2. Embed in cell-laden gel
3. Remove template

Build the channel shape first, solidify material around it, then remove the template.

2. Co-print several materials (Kolesky et al.)

1. Prepare bioinks
2. Co-print cells and channel ink
3. Remove channel ink

Place cell-containing material and a temporary space-holder for the channel together.

3. Shape the surrounding gel with light (Grigoryan et al.)

1. Prepare photocurable gel
2. Pattern it with light
3. Wash out uncured gel

A light pattern defines the void without printing a solid sacrificial template.

4. Write inside densely packed cells (SWIFT)

1. Pack cell aggregates
2. Write sacrificial ink inside
3. Remove ink and perfuse

Write a route afterward through a material already rich in cells.

• Sacrificial mold (Miller et al., 2012): a rigid filament network of carbohydrate glass was printed and embedded in cell-laden tissue as a mold; it could be lined with endothelial cells, giving cylindrical networks that could be perfused with blood under high-pressure pulsatile flow. The perfused channels preserved the metabolic function of primary rat hepatocytes that was otherwise suppressed in the core of the tissue. The authors say the channel geometry, endothelialisation and tissue outside the channels can be controlled independently, and that it suits a range of cells, extracellular matrices and crosslinking methodsSourced
• Co-printing (Kolesky et al., 2014): they reported a method of printing several bioinks together in three dimensions to make heterogeneous tissue constructs with vessels, multiple cell types and extracellular matrixSourced
• Stereolithography (Grigoryan et al., 2019): adding food dyes to photopolymerizable hydrogels as biocompatible, powerful light absorbers, they used projection stereolithography to make, in minutes, transparent gels containing intravascular fluid mixers and bicuspid valves. They also show an example using a biodegradable hydrogel carrier in a rodent model of chronic liver injurySourced
• Embedded printing (Skylar-Scott et al., 2019): they reported the SWIFT method, which gathers hundreds of thousands of iPS cell-derived organoids into a dense cell mass of about 10⁸ cells/mL and writes perfusable channels into it. The heart tissue beat synchronously for 7 daysSourced
• Printing collagen (Lee et al., 2019): with the FRESH method, controlling gelation by pH, they printed collagen structures at scales from capillaries to a whole heart with a filament resolution of 20 µm. A ventricle seeded with human cardiomyocytes showed synchronised contraction and wall thickening (up to 14% at peak systole)Sourced

8. Clinical examples and their stage

The Kyoto University Hospital example follows Ikeguchi et al. (2024) [Source 16]; the other two follow the ClinicalTrials.gov entries [Sources 17 and 18] and a commentary paper [Source 19]. Where the origin of the cells (autologous or allogeneic) is not clear from the registry entry, we have kept to what it says.

The Kyoto University Hospital trial is notable for stacking the spheroids themselves, without scaffold material (hydrogel). In 2015, Itoh et al., using the same needle-array method, made a tubular tissue of 1.5 mm inner diameter from 500 spheroids of endothelial cells, smooth muscle cells and fibroblasts, grafted it into the abdominal aorta of rats, and reported that every graft stayed open and a layer of endothelial cells was confirmed 5 days after graftingSourced.

As for approved products, none of the product names on the FDA list of approved cellular and gene therapy products (updated 17 September 2026) could be confirmed as made by bioprinting [Source 20]Sourced. We have not checked approved products in other countries and regions exhaustivelyNot yet confirmed.

9. A materials engineer's view (2): a bioink is the raw material of a living product

10. Open issues, and what this article could not confirm

(1) Viability is no substitute for function

Many reports give viability after printing, but whether the cells keep their function and what happens in the long term need separate evaluation. The review by Xu et al. also says that, besides viability, the proliferation and differentiation capacity of stem cells must be kept [Source 3]Sourced.

(2) For vascular networks, there is a gap between making tubes and working as tissue

The reports in chapter 7 show that perfusable tubes can be made. As for the barrier function of the endothelial cells lining the tubes, long-term maintenance under blood flow, and coordination with surrounding tissue, we could not confirm enough within the scope of this surveyNot yet confirmed.

(3) Clinical evidence is at the small-study stage

The human trials we could confirm involve 3 patients, 2 (terminated) and 1. They are not on a scale that can evaluate efficacy, nor can they be compared with other treatments [Sources 16 to 18].

(4) Regulatory framework

The review by Ozbolat et al. lists regulatory concerns on the way to commercialisation as a challenge [Source 4]Sourced. We have not confirmed any FDA or PMDA guidance specific to bioprintingNot yet confirmed.

(5) What this article could not confirm

• Details of the Seoul St. Mary's Hospital tracheal transplant in a peer-reviewed original paper (only the registry entry and a commentary paper were confirmed)
• Results of the AuriNovo trial
• Approval status of bioprinted products in other countries and regions, including Japan and Europe
• Public specifications and standards for bioinks (such as standardised methods for evaluating printability)
• Market-size estimates (not covered, because we do not use market-research estimates)

11. Glossary

12. References

1. Groll J et al. "A definition of bioinks and their distinction from biomaterial inks", Biofabrication 11:013001 (2018) — doi.org
2. Moroni L et al. "Biofabrication: A Guide to Technology and Terminology", Trends Biotechnol 36:384 (2018) — doi.org
3. Xu HQ et al. "A review on cell damage, viability, and functionality during 3D bioprinting", Mil Med Res 9:70 (2022) (PMC) — pmc.ncbi.nlm.nih.gov
4. Ozbolat IT, Hospodiuk M "Current advances and future perspectives in extrusion-based bioprinting", Biomaterials 76:321 (2016) — doi.org
5. Nair K et al. "Characterization of cell viability during bioprinting processes", Biotechnol J 4:1168 (2009) — doi.org
6. Aguado BA et al. "Improving viability of stem cells during syringe needle flow through the design of hydrogel cell carriers", Tissue Eng Part A 18:806 (2012) — doi.org
7. Cui X et al. "Cell damage evaluation of thermal inkjet printed Chinese hamster ovary cells", Biotechnol Bioeng 106:963 (2010) — doi.org
8. Ouyang L et al. "Effect of bioink properties on printability and cell viability for 3D bioplotting of embryonic stem cells", Biofabrication 8:035020 (2016) — doi.org
9. Pati F et al. "Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink", Nat Commun 5:3935 (2014) (PMC) — doi.org
10. Miller JS et al. "Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues", Nat Mater 11:768 (2012) — doi.org
11. Kolesky DB et al. "3D bioprinting of vascularized, heterogeneous cell-laden tissue constructs", Adv Mater 26:3124 (2014) — doi.org
12. Grigoryan B et al. "Multivascular networks and functional intravascular topologies within biocompatible hydrogels", Science 364:458 (2019) — doi.org
13. Skylar-Scott MA et al. "Biomanufacturing of organ-specific tissues with high cellular density and embedded vascular channels", Sci Adv 5:eaaw2459 (2019) — doi.org
14. Lee A et al. "3D bioprinting of collagen to rebuild components of the human heart", Science 365:482 (2019) — doi.org
15. Itoh M et al. "Scaffold-Free Tubular Tissues Created by a Bio-3D Printer Undergo Remodeling and Endothelialisation when Implanted in Rat Aortae", PLoS One 10:e0136681 (2015) — doi.org
16. Ikeguchi R et al. "Peripheral nerve regeneration following scaffold-free conduit transplant of autologous dermal fibroblasts: a non-randomised safety and feasibility trial", Commun Med 4:12 (2024) (PMC) — doi.org
17. ClinicalTrials.gov "NCT04399239: AuriNovo for Auricular Reconstruction" — clinicaltrials.gov
18. ClinicalTrials.gov "NCT06051747: Patient-Customized Bioprinting Technology for Practical Regeneration of the Respiratory Tract (Trachea)" — clinicaltrials.gov
19. Shah AM et al. "Artificial trachea transplant: Tale of two stories", Artif Organs 48:575 (2024) — doi.org
20. US FDA "Approved Cellular and Gene Therapy Products" (updated 17 September 2026) — fda.gov
21. Blaeser A et al. "Controlling Shear Stress in 3D Bioprinting is a Key Factor to Balance Printing Resolution and Stem Cell Integrity", Adv Healthc Mater 5:326 (2016) — doi.org
22. Murphy SV, Atala A "3D bioprinting of tissues and organs", Nat Biotechnol 32:773 (2014) — doi.org

13. Claim-to-source audit

Last updated 1 October 2026. Sources are limited to primary material (peer-reviewed papers and reviews, registry entries on ClinicalTrials.gov and jRCT, and the FDA list of approved products). Market-size and share estimates are not used. Because the article includes structural readings and interpretations from the materials and process side, those are marked as Commentary and kept separate from sourced fact. Details of the Seoul St. Mary's Hospital tracheal transplant in an original paper, results of the AuriNovo trial, the barrier function and long-term maintenance of endothelium in vessels, approval status in other regions, public specifications for bioinks, and regulatory guidance specific to bioprinting could not be confirmed in published primary sources, so they are not covered or are treated as not yet confirmed. All figures are for explanation. Figs. 1, 2, 3, 5 and 6 are conceptual diagrams (vector drawings), Fig. 4 is a drawing that includes our calculation (vector drawing), and the hero image is AI-generated; none of them shows a real machine, tissue or cell. This article explains technology and is neither medical advice nor a recommendation of any particular treatment or product.