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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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