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Parametric Optimization of 3D Printed Hydrogel-Based Cardiovascular Stent

Abstract

Purpose

This study aimed to develop personalized biodegradable stent (BDS) for the treatment of coronary heart disease. Three-dimensional (3D) printing technique has offered easy and fast fabrication of BDS with enhanced reproducibility and efficacy.

Methods

A variety of BDS were printed with 3 types of hydrogel (~5 ml) resources (10%w/v sodium alginate (SA), 10%w/v cysteine-sodium alginate (SA-CYS), and 10%w/v cysteine-sodium alginate with 0.4%w/v PLA-nanofibers (SA-CYS-NF)) dispersed from an 22G print head nozzle attached to the BD-syringe. The printability of hydrogels into 3D structures was examined based on such variables as hydrogel’s viscosity, printing distance, printing speed and the nozzle size.

Results

It was demonstrated that alginate composition (10%w/v) offered BDS with sufficient viscosity that defined the thickness and swelling ratio of the stent struts. The thickness of the strut was found to be 338.7 ± 29.3 μm, 262.5 ± 14.7 μm and 237.1 ± 14.7 μm for stents made of SA, SA-CYS and SA-CYS-NF, respectively. SA-CYS-NF stent displayed the highest swelling ratio of 38.8 ± 2.9% at the initial 30 min, whereas stents made of SA and SA-CYS had 23.1 ± 2.4% and 22.0 ± 2.4%, respectively.

Conclusion

The printed stents had sufficient mechanical strength and were stable against pseudo-physiological wall shear stress. An addition of nanofibers to alginate hydrogel significantly enhanced the biodegradation rates of the stents. In vitro cell culture studies revealed that stents had no cytotoxic effects on human umbilical vein endothelial cells (HUVECs) and Raw 264.7 cells (i.e., Monocyte/macrophage-like cells), supporting that stents are biocompatible and can be explored for future clinical applications.

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Abbreviations

3D:

Three-dimensional

BD:

Becton, Dickinson and Company

BDS:

Biodegradable stent

CAD:

Coronary artery diseases

DES:

Drug-eluting stents

DHR3:

Discovery Hybrid Rheometer

DMEM:

Dulbecco’s modified eagle’s medium

EDC:

1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide

FBS:

Fetal bovine serum

HCl:

Hydrochloric acid

HFIP:

Hexafluoro-2-propanol

HUVECs:

human umbilical vein endothelial cells

IPA:

2-isopropanol

ISR:

In-stent restenosis

LVR:

Linear viscoelastic region

MWCO:

Molecular weight cutoff

NaCl:

Sodium chloride

PBS:

Phosphate-buffered saline

PI:

Propidium iodide

PLA:

Poly-lactic acid

SA:

Sodium alginate

SA-CYS:

Cysteine-sodium alginate

SA-CYS-NF:

Cysteine-sodium alginate with PLA nanofibers

SEM:

Scanning electron microscopy

STL:

Standard Tessellation Language

WSS:

Wall shear stress

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Acknowledgments and Disclosures

This work was supported by faculty bridge research fund from School of Pharmacy, UMKC. We would like to thank Dr. Zahra Niroobakhsh and Mr. Houman Honaryar for allowing us to use the Rheometer and assistance in handling the Rheometer. There is no financial/commercial conflict of interest.

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Correspondence to Chi H. Lee.

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Veerubhotla, K., Lee, Y. & Lee, C.H. Parametric Optimization of 3D Printed Hydrogel-Based Cardiovascular Stent. Pharm Res 38, 885–900 (2021). https://doi.org/10.1007/s11095-021-03049-1

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  • DOI: https://doi.org/10.1007/s11095-021-03049-1

Key Words

  • 3D printing technique
  • alginate hydrogel
  • cell viability
  • personalized biodegradable stent