TY - JOUR
T1 - Timing effect of intramyocardial hydrogel injection for positively impacting left ventricular remodeling after myocardial infarction
AU - D'Amore, Antonio
AU - D'Amore, Antonio
AU - Tchao, Jason
AU - Jiang, Hongbin
AU - Zhu, Yang
AU - Wagner, William R.
AU - Yoshizumi, Tomo
AU - Sakaguchi, Hirokazu
AU - Tobita, Kimimasa
PY - 2016
Y1 - 2016
N2 - Intramyocardial injection of various injectable hydrogel materials has shown benefit in positively impacting the course of left ventricular (LV) remodeling after myocardial infarction (MI). However, since LV remodeling is a complex, time dependent process, the most efficacious time of hydrogel injection is not clear. In this study, we injected a relatively stiff, thermoresponsive and bioabsorbable hydrogel in rat hearts at 3 different time points - immediately after MI (IM), 3 d post-MI (3D), and 2 w post-MI (2W), corresponding to the beginnings of the necrotic, fibrotic and chronic remodeling phases. The employed left anterior descending coronary artery ligation model showed expected infarction responses including functional loss, inflammation and fibrosis with distinct time dependent patterns. Changes in LV geometry and contractile function were followed by longitudinal echocardiography for 10 w post-MI. While all injection times positively affected LV function and wall thickness, the 3D group gave better functional outcomes than the other injection times and also exhibited more local vascularization and less inflammatory markers than the earlier injection time. The results indicate an important role for injection timing in the increasingly explored concept of post-MI biomaterial injection therapy and suggest that for hydrogels with mechanical support as primary function, injection at the beginning of the fibrotic phase may provide improved outcomes.
AB - Intramyocardial injection of various injectable hydrogel materials has shown benefit in positively impacting the course of left ventricular (LV) remodeling after myocardial infarction (MI). However, since LV remodeling is a complex, time dependent process, the most efficacious time of hydrogel injection is not clear. In this study, we injected a relatively stiff, thermoresponsive and bioabsorbable hydrogel in rat hearts at 3 different time points - immediately after MI (IM), 3 d post-MI (3D), and 2 w post-MI (2W), corresponding to the beginnings of the necrotic, fibrotic and chronic remodeling phases. The employed left anterior descending coronary artery ligation model showed expected infarction responses including functional loss, inflammation and fibrosis with distinct time dependent patterns. Changes in LV geometry and contractile function were followed by longitudinal echocardiography for 10 w post-MI. While all injection times positively affected LV function and wall thickness, the 3D group gave better functional outcomes than the other injection times and also exhibited more local vascularization and less inflammatory markers than the earlier injection time. The results indicate an important role for injection timing in the increasingly explored concept of post-MI biomaterial injection therapy and suggest that for hydrogels with mechanical support as primary function, injection at the beginning of the fibrotic phase may provide improved outcomes.
KW - CD31; Cytokines; Female; Heart Ventricles; Hydrogel; Inflammation Mediators; Injections; Macrophages; Myocardial Infarction; Myocardium; Neutrophil Infiltration; Rats
KW - Cardiac tissue engineering; Hydrogel; Injectable materials; Intervention timing; Myocardial infarction; Actins; Animals; Antigens
KW - Inbred Lew; Time Factors; Ventricular Remodeling; Biomaterials; Bioengineering; Ceramics and Composites; Mechanics of Materials; Biophysics
KW - CD31; Cytokines; Female; Heart Ventricles; Hydrogel; Inflammation Mediators; Injections; Macrophages; Myocardial Infarction; Myocardium; Neutrophil Infiltration; Rats
KW - Cardiac tissue engineering; Hydrogel; Injectable materials; Intervention timing; Myocardial infarction; Actins; Animals; Antigens
KW - Inbred Lew; Time Factors; Ventricular Remodeling; Biomaterials; Bioengineering; Ceramics and Composites; Mechanics of Materials; Biophysics
UR - http://hdl.handle.net/10447/222133
UR - http://www.journals.elsevier.com/biomaterials/
M3 - Article
VL - 83
SP - 182
EP - 193
JO - Biomaterials
JF - Biomaterials
SN - 0142-9612
ER -