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Bio 3D Printing Delivers a Graft That Bends to 9 mm Without Occlusion

When Bypass Vessels Run Short,
Bio 3D Printing Delivers a Graft That Bends to 9 mm Without Occlusion

PanoSpace · Frontier Review

Scientific Reports · Sharif University of Technology


For coronary bypass and lower-limb revascularization, the ideal material is the patient’s own vessel — but when autologous vessels are insufficient or mismatched in caliber, surgeons must fall back on synthetic grafts. The trouble: small-diameter vascular grafts (SDVGs, <6 mm) have yet to deliver a version clinicians can safely use — prone to thrombosis, prone to kinking, difficult to suture.

In 2025, a team at Sharif University of Technology published a study in Scientific Reports: using melt electrowriting (MEW) from the bio 3D printing toolbox, a thermoplastic polyurethane (TPU) elastic skeleton was printed as the graft’s “inner lining,” then wrapped with an electrospun nanofiber “outer skin” mimicking the extracellular matrix. Bends to a 9.14 mm radius without occluding, releases 72% of heparin over 30 days, and tensile strength exceeding the coronary artery. Of the three-layer vascular wall challenge, two-layer construction has covered half the ground.

Highlights

  • Three Achilles’ heels of small-diameter grafts: thrombosis, kinking, suture pull-out
  • 215 °C printing yields 69 µm TPU microfibers
  • Three skeleton densities compared — the “hybrid” design wins on both strength and flexibility
  • Kink radius 9.14 mm, suture retention 2.13 N, endothelial layer formed within 7 days
9.14 mm kink radius (hybrid skeleton)
72% cumulative heparin release over 30 days
7.09 MPa ultimate tensile strength

PART 01 The “Material Shortage” in Bypass Surgery: Below 6 mm, Synthetic Grafts Fail

Global cardiovascular disease deaths rose from about 12.1 million in 1990 to about 18.6 million in 2019 (GBD data cited in the paper). Drugs can control lipids and blood pressure, but for severe stages where vessels are already occluded, surgery remains the mainstay: harvest a vessel from elsewhere in the patient’s body and construct a “bypass” around the blockage. Autologous vessels carry low immunogenic risk and come with their own endothelial cells — clinically, they are the first choice whenever available. But they have two hard limits: the patient’s own vessels may already be diseased, or their caliber may not match the defect site.

This is where synthetic grafts come in. Large-diameter synthetic grafts (e.g., Dacron) have long been mature, but small-diameter vascular grafts (SDVGs, <6 mm) remain a hard nut: slow blood flow, easy thrombosis; material too stiff, compliance cannot keep up with the pulse; suture fixation fails under thread tension; post-implantation intimal hyperplasia continues to narrow the lumen. The paper sets a “passing grade”: burst pressure, tensile strength, and suture retention must all exceed the levels of human arteries (e.g., coronary artery tensile strength 6.4 ± 0.1 MPa, suture retention 2.01 ± 0.01 N).

One more “physical” problem plagues researchers — kinking. A synthetic graft must bend along joints and along the vessel’s course; once it bends to a certain radius and the lumen is crushed flat, blood flow instantly shifts from laminar to turbulent, platelets aggregate in the turbulent zone, and thrombotic risk spikes. This “minimum bend radius without kinking” is called the kink radius — the smaller the value, the more the vessel can bend without collapsing.


PART 02 Bilayer Construction: Printed Skeleton Inside, Electrospun “ECM” Outside

The team’s design follows a “division of labor between inside and outside.”

Inside: using melt electrowriting (MEW) — the microfiber-focused direct-writing technology within the bio 3D printing family — a regular mesh skeleton of thermoplastic polyurethane (TPU) is printed, providing strength and kink resistance;

Outside: using co-electrospinning, a PCL/PU/gelatin nanofiber membrane is wrapped outside the skeleton, mimicking the fibrous structure of the natural vascular extracellular matrix (ECM), providing cell adhesion and leak prevention, with the anticoagulant heparin blended into the fibers for sustained release.

Each of the three materials has a specific role: PU provides elasticity and blood compatibility; PCL degrades slowly and maintains structural integrity; gelatin is hydrophilic and helps cells grip the surface. The paper notes that no prior study had combined a MEW scaffold with a PCL/PU/gelatin co-electrospun graft — this combination must simultaneously address kink radius, flexibility, and biocompatibility.


PART 03 215 °C Prints 69 µm Fine Fibers

TPU at 215 °C behaves in melt and electrohydrodynamics similarly to the commonly used PCL, so the team started from PCL’s already-optimized parameters and fine-tuned: nozzle moving at 30 mm/s, melt flow 10 µL/min, nozzle-to-mandrel distance 3 mm, voltage 3500 V — stable printing at room temperature. Fiber density is controlled by mandrel rotation speed: 30 rpm prints a dense structure, 45 rpm a loose one, with 10 layers per structure type.

Research view | Full MEW printing parameters

Motion control: nozzle paths generated as G-code by slicing software; mandrel rotation driven by stepper motor + microstep driver + open-source control board

Process parameters: nozzle traverse speed 30 mm/s; melt flow 10 µL/min; nozzle-to-mandrel distance 3 mm; voltage 3500 V; room temperature environment

Structure design: mandrel rotation 30 rpm (dense) / 45 rpm (loose); 10 layers each; hybrid structure is 5 dense layers + 5 loose layers; TPU molecular weight 80–100 kDa

Not reported in the paper: electric field distribution at the receiving distance, interlayer heating strategy, printing throughput and yield


PART 04 Choosing Among Three Densities: Dense, Loose, or “Hybrid”?

MEW’s advantage is that fibers go exactly where they are placed. Under SEM, the three skeletons are clearly distinct: dense structure parallel fiber spacing 0.818 ± 0.045 mm, loose structure 3.061 ± 0.381 mm, with fiber crossing angles around 59°; MEW fiber average diameter 69.117 ± 7.353 µm. The co-electrospun layer wrapped outside is at another order of magnitude — fiber diameter 662.86 ± 335.51 nm, pore size 638.65 ± 364.93 nm, small enough to block blood leakage while leaving a door for cells to crawl in.

The formed bilayer vessel’s inner diameter is about 5.85 ± 0.14 mm, falling neatly into the small-diameter range. Cross-sectional SEM shows the MEW skeleton and electrospun layer tightly bonded with no delamination — mechanical load transfer can be continuous. The micron-scale skeleton leaves “large” pores for cells to crawl in; the nanometer-scale electrospun layer provides “small” fibers for cells to grip — two scales stacked on one tube.


PART 05 Anticoagulation and Degradation Checkup: Two “Drug Reservoirs” Relay Heparin Release

Thrombosis is the number-one cause of small-diameter synthetic graft failure, and the team’s countermeasure is to weave heparin directly into the outer fibers — with two reservoirs of different properties: the hydrophilic, fast-degrading gelatin layer handles the first rapid release; the hydrophobic, stable PCL/PU layer handles the long slow trickle. Measured results: the gelatin layer released all of its heparin within 19 days, while the PCL/PU layer cumulatively released 72% over 30 days. There is a burst on day one — which is exactly useful, since the earliest post-implantation window carries the highest thrombotic risk; a high-concentration anticoagulant wave first to hold the line, then a slower sustained escort.

Hydrophilicity matters equally — cells do not like hydrophobic surfaces. Contact angle tests: the TPU MEW layer at 144.1°, the PCL/PU electrospun layer at 121.1° — both typical “water-repelling” faces; with gelatin blended in, the angle dropped to 36.87 ± 1.2°, and the gelatin electrospun layer went even lower to 23.88°. Degradation tests (PBS, 37 °C, 21 days) follow the same logic: PCL/PU/gelatin layer 23.889 ± 1.340%, PCL/PU layer 9.847 ± 0.796%, TPU MEW layer slowest at only 2.791 ± 0.260% — the outer layer progressively gives way to newly formed tissue while the inner skeleton holds long-term support, each doing its part at its own pace.

Research view | Spinning formulation and physicochemical data

PCL/PU solution: PCL:PU = 50:50, dissolved in DMF:chloroform = 2:3, 12 wt%; Span80 25 µL added per 5 mL, stirred 2 h, then heparin 250 µL added dropwise and stirred 4 h

Gelatin solution: 20 wt% gelatin in glacial acetic acid:water = 3:2, stirred at 40 °C for 4 h; injectable heparin 1 mL added per 4 mL and stirred 1 h

Co-electrospinning: PCL/PU side flow 0.7 mL/h, distance 17 cm, voltage 18 kV, 18 G blunt needle; gelatin side flow 0.4 mL/h, distance 15 cm, voltage 21 kV; aluminum rod collector 5.81 mm diameter, 700 rpm

Key values: electrospun fibers 662.86 ± 335.51 nm; pore size 638.65 ± 364.93 nm; contact angle 144.1° (TPU MEW) / 121.1° (PCL/PU) / 36.87° (with gelatin) / 23.88° (gelatin layer); 21-day degradation 23.889% (PCL/PU/Gel), 9.847% (PCL/PU), 2.791% (TPU MEW)

Raw materials: medical-grade PU (Rx85A, Mn=48,000), PCL (Mn=48,000), porcine type A gelatin, heparin sodium injection 5000 IU/mL


PART 06 The Mechanical Test: Strength Must Hold, and the Vessel Must Still Bend

Mechanics is the protagonist of this section, and it is a see-saw: denser fibers mean higher strength and lower flexibility. Ultimate tensile strength: dense 9.04 ± 0.28 MPa > hybrid 7.09 ± 0.16 MPa > loose; Young’s modulus also rises with density, dense 37.67 ± 1.04 MPa, hybrid 22.78 ± 0.91 MPa. Compared to the coronary artery (tensile 6.4 ± 0.1 MPa, modulus 1.55 ± 0.1 MPa, data cited in the paper), both the dense and hybrid designs leave it behind. Elongation at break reverses the trend: hybrid 408 ± 2.5%, dense 321.4 ± 3.7%, both exceeding the carotid artery’s 225 ± 1%.

Suture retention — the “will it tear when sewn” concern of every surgeon: pure electrospun layer 1.97 ± 0.08 N, with skeleton added: loose 1.99, hybrid 2.13, dense 3.31 ± 0.11 N. Reference values for carotid and coronary arteries are 1.96 ± 0.10 and 2.01 ± 0.10 N; both hybrid and dense designs cross the line, and far exceed the prior record of 0.37 ± 0.03 N for a MEW+electrospun bilayer graft of the same class (cited in the paper).

The protagonist arrives — kink radius. The pure electrospun layer kinks at 38.72 ± 0.44 mm, almost unusable near joints; with the MEW skeleton added, the kink radius drops precipitously: hybrid bilayer 9.14 ± 0.10 mm, loose bilayer 6.95 ± 0.31 mm, dense bilayer 12.57 ± 0.18 mm. Compliance (diameter change under 80–120 mmHg) mirrors the other face: pure electrospun layer most compliant (2.31 ± 0.12 %/40 mmHg), lower with denser skeleton — strength and elasticity are inherently antagonistic. Burst pressure 1350 ± 140 mmHg, though lower than great saphenous vein (2200) and internal mammary artery (5000), is already ~9.5× mean blood pressure. Overall, the hybrid design wins the “strength is enough + it still bends” sweet spot, and was selected for all subsequent biological validation.

Research view | Mechanical test methods and full data

Test methods: uniaxial tension (universal testing machine, 200 N load cell, 2 mm/min, specimen 1×2 cm², PBS soak 2 h); suture retention (4-0 monofilament suture inserted 2 mm from end, pulled to rupture at 5 mm/min); compliance (80→120 mmHg water infusion measuring diameter change); burst pressure (3 cm segment infused to leakage); kink radius (both ends bent until crease appears). All n=3

Hybrid bilayer (final design): UTS 7.09 ± 0.16 MPa; Young’s modulus 22.78 ± 0.91 MPa; elongation 408 ± 2.5%; suture retention 2.13 ± 0.09 N; kink radius 9.14 ± 0.10 mm; wall cross-sectional area 9.346×10⁻⁷ m²

Native vessel reference (cited in the paper): coronary UTS 6.4 ± 0.1 MPa, modulus 1.55 ± 0.1 MPa, suture retention 2.01 ± 0.10 N; carotid elongation 225 ± 1%, suture retention 1.96 ± 0.10 N; great saphenous burst 2200 mmHg; internal mammary 5000 mmHg

Honest note: compliance 2.31 %/40 mmHg (pure electrospun layer) is below human arterial reference values, and drops further with skeleton density; burst pressure falls short of native artery levels — the paper argues safety margin via “~9.5× mean blood pressure,” not avoiding the gap


PART 07 Do Platelets “Lie Flat” or “Clump”? Seven Days to Grow an Endothelial Layer

Whether anticoagulation works, platelets are the most honest referee. Platelet-rich plasma was laid on the material surface for 3 h: in the non-heparinized control, platelets spread extensively, extending pseudopodia — the prelude to the coagulation cascade; on the heparinized bilayer graft surface, platelets were markedly fewer, spherical in shape, with no activated spreading. Heparin’s sustained release pinned the “first scene of coagulation” at the starting point.

Cell experiments used human umbilical vein endothelial cells (HUVEC), seeded at 35,000 per sample. MTT proliferation curves (optical density) climbed steadily over 7 days: bilayer graft from 0.347 ± 0.0065 at day 1 to 0.627 ± 0.005 at day 7; pure electrospun layer 0.386 → 0.666; TPU MEW layer started slowest due to hydrophobicity (0.333 → 0.584). From day 7 to 21 all groups plateaued — the paper interprets this as the endothelial layer having grown to confluence, with proliferation giving way to steady-state maintenance. Live/dead staining and SEM both confirm the path: day-1 cells were still round and “just landed,” by day 7 they had spread into a continuous monolayer endothelium, firmly gripping the fibers.

This “rapid endothelialization + local heparinization” combination is precisely why the paper believes it can address the thrombosis problem in small-diameter grafts: the endothelial layer is a natural antithrombotic lining; heparin sustained release covers the gap before endothelium grows in.

Research view | Cell experiments and anticoagulation test design

Cells: HUVEC (passage 3), DMEM + 10% FBS, 35,000 per sample / 1 mL; samples pre-treated with 70% ethanol, UV sterilized, overnight medium preconditioning; TCPS as control

Assays: MTT (days 1/3/7/14/21, 570 nm); live/dead staining (acridine orange / propidium iodide, 45 min); SEM adhesion morphology (2.5% glutaraldehyde fixation, gradient ethanol dehydration)

Platelet adhesion: platelet-rich plasma (10⁸ /mL) incubated at 37 °C for 3 h, 2.5% glutaraldehyde fixation, SEM counting in three random fields

Key values: MTT optical density bilayer 0.347 ± 0.0065 (d1) → 0.627 ± 0.005 (d7) → 0.657 ± 0.011 (d21); MEW 0.333 → 0.584 → 0.664; electrospun layer 0.386 → 0.666 → 0.607; statistics one-way/two-way ANOVA, p<0.05 significant


PART 08 How Far From the Sickbed: Three Doors Not Yet Closed

The paper is direct about limitations.

First, all validation is in vitro — no animal implantation, no real blood-flow shear; whether heparin release kinetics align with clinical anticoagulation thresholds, and the graft’s degradation and structural stability over months in vivo, remain unknown.

Second, the “deep water” endothelial function tests are still pending: nitric oxide synthase activity, monocyte adhesion, vascular smooth muscle cell proliferation and other indicators are for the next stage; co-culture (endothelium + smooth muscle) is required to reproduce real vascular cell dialogue.

Third, engineering threshold: MEW and electrospinning scale-up must simultaneously preserve structural consistency, drug loading, and batch-to-batch stability of degradation rates — plus clear regulatory hurdles.

But this study has assembled the key pieces that a small-diameter synthetic graft needs: a bio 3D-printed elastic skeleton that bends to 9.14 mm without kinking, a biomimetic nanofiber sheath that releases heparin slowly, a mechanical report card that surpasses the coronary artery, and a 7-day endothelialization validation chain. From this custom-built equipment to these data, there is still a long road to “a synthetic graft that can enter the operating room” — but the route is at least proven feasible.


Closing Thoughts

Small-diameter synthetic grafts have been in play for over half a century;
what has held them back has never been one property falling short,
but good properties fighting each other:
want strength, must be stiff; want flexibility, must be soft; want anticoagulation, must release drug; release too fast, strength drops.
This study’s answer is very “engineer”:
don’t make one material do all the work
— the printed skeleton handles mechanics and kink resistance, the electrospun sheath handles biomimicry and drug release;
each does its own job, then the two layers interlock into one.

MEW’s role here is pure: micron-scale fibers, precisely placed fiber by fiber — exactly the technology that first truly put “skeleton design freedom” into researchers’ hands. The vasculature is one of the most “unreasonable” mechanical environments in the human body; a material solution that can stand its ground here often also inspires the construction of other luminal tissues.


📄 Paper Information

Title: Shahverdi M, Shaygani H, Soltani M, et al. Fabrication of a low-kink-radius bilayer vascular scaffold incorporating a TPU stent fabricated via melt electrowriting and an electrospun PCL/PU/gelatin layer. Scientific Reports, 2025, 15:24894.

DOI: 10.1038/s41598-025-10547-4

Author affiliation: Sharif University of Technology, Iran

This article is a research literature interpretation; all content is quoted from the published paper, for scientific knowledge dissemination only, and does not constitute any diagnostic or treatment recommendation, nor any product performance promise. The technologies and materials described have not entered clinical application; experimental data come from in vitro studies.

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