Preliminary Investigation on Efficacy and Safety of Substance P-Coated Stent for Promoting Re-Endothelialization: A Porcine Coronary Artery Restenosis Model
10.1007/s13770-023-00608-y
- Author:
Dae Sung PARK
1
;
Seok OH
;
Yu Jeong JIN
;
Mi Hyang NA
;
Munki KIM
;
Jeong Ha KIM
;
Dae Young HYUN
;
Kyung Hoon CHO
;
Young Joon HONG
;
Ju Han KIM
;
Youngkeun AHN
;
Manuel HERMIDA-PRIETO
;
José Manuel VÁZQUEZ-RODRIGUEZ
;
Juan Luis GUTIÉRREZ- CHICO
;
Luis MARINÃS-PARDO
;
Kyung Seob LIM
;
Jun-Kyu PARK
;
Dae-Heung BYEON
;
Young-Nan CHO
;
Seung-Jung KEE
;
Doo Sun SIM
;
Myung Ho JEONG
Author Information
1. The Korea Cardiovascular Stent Research Institute, Chonnam National University, Gwangju, Korea
- Publication Type:ORIGINAL ARTICLE
- From:
Tissue Engineering and Regenerative Medicine
2024;21(1):53-64
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND:Current polymer-based drug-eluting stents (DESs) have fundamental issues about inflammation and delayed re-endothelializaton of the vessel wall. Substance-P (SP), which plays an important role in inflammation and endothelial cells, has not yet been applied to coronary stents. Therefore, this study compares poly lactic-co-glycolic acid (PLGA)-based everolimus-eluting stents (PLGA-EESs) versus 2-methacryloyloxyethyl phosphorylcholine (MPC)-based SP-eluting stents (MPC-SPs) in in-vitro and in-vivo models.
METHODS:The morphology of the stent surface and peptide/drug release kinetics from stents were evaluated. The invitro proliferative effect of SP released from MPC-SP is evaluated using human umbilical vein endothelial cell. Finally, the safety and efficacy of the stent are evaluated after inserting it into a pig’s coronary artery.
RESULTS:Similar to PLGA-EES, MPC-SP had a uniform surface morphology with very thin coating layer thickness (2.074 lm). MPC-SP showed sustained drug release of SP for over 2 weeks. Endothelial cell proliferation was significantly increased in groups treated with SP (n = 3) compared with the control (n = 3) and those with everolimus (n = 3) (SP:118.9 ± 7.61% vs. everolimus: 64.3 ± 12.37% vs. the control: 100 ± 6.64%, p < 0.05). In the animal study, the percent stenosis was higher in MPC-SP group (n = 7) compared to PLGA-EES group (n = 7) (MPC-SP: 28.6 ± 10.7% vs. PLGAEES: 16.7 ± 6.3%, p < 0.05). MPC-SP group showed, however, lower inflammation (MPC-SP: 0.3 ± 0.26 vs. PLGAEES: 1.2 ± 0.48, p < 0.05) and fibrin deposition (MPC-SP: 1.0 ± 0.73 vs. PLGA-EES: 1.5 ± 0.59, p < 0.05) around the stent strut. MPC-SP showed more increased expression of cluster of differentiation 31, suggesting enhanced reendothelialization.
CONCLUSION:Compared to PLGA-EES, MPC-SP demonstrated more decreased inflammation of the vascular wall and enhanced re-endothelialization and stent coverage. Hence, MPC-SP has the potential therapeutic benefits for the treatment of coronary artery disease by solving limitations of currently available DESs.
