1.Preliminary Investigation on Efficacy and Safety of Substance P-Coated Stent for Promoting Re-Endothelialization: A Porcine Coronary Artery Restenosis Model
Dae Sung PARK ; 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
Tissue Engineering and Regenerative Medicine 2024;21(1):53-64
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.
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