Infarct stabilization and cardiac repair with a VEGF-conjugated, injectable hydrogel

被引:121
作者
Wu, Jun [1 ,2 ]
Zeng, Faquan [1 ,2 ]
Huang, Xi-Ping [1 ,2 ]
Chung, Jennifer C-Y [1 ,2 ]
Konecny, Filip [1 ,2 ]
Weisel, Richard D. [1 ,2 ]
Li, Ren-Ke [1 ,2 ]
机构
[1] Univ Toronto, Div Cardiovasc Surg, Univ Hlth Network, Toronto, ON M5G 1L7, Canada
[2] Univ Toronto, Dept Surg, Toronto, ON M5G 1L7, Canada
基金
加拿大健康研究院;
关键词
Angiogenesis; Cardiac tissue engineering; Cytokine (VEGF); Hydrogel; In vivo test; Thermally responsive material; GROWTH-FACTOR DELIVERY; FUNCTIONAL IMPROVEMENT; CELLS; HEART; ANGIOGENESIS; SCAFFOLDS; EXPANSION; SURVIVAL; CHITOSAN; POLYMER;
D O I
10.1016/j.biomaterials.2010.08.098
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Injectable scaffolds made of biodegradable biomaterials can stabilize a myocardial infarct and promote cardiac repair Here we describe the synthesis of a new temperature-sensitive aliphatic polyester hydrogel (HG) conjugated with vascular endothelial growth factor (VEGF) and evaluate its effects on cardiac recovery after a myocardial infarction (MI) Seven days after coronary ligation in rats PBS HG or HG mixed or conjugated with VEGF (HG + VEGF or HG-VEGF respectively) was injected around the infarct (n = 8-11/group) Function was evaluated by echocardiography at multiple time points Pressure volume measurements were taken and infarct morphometry and blood vessel density were assessed at 35 days after injection HG-VEGF provided localized sustained VEGF function Compared with outcomes in the PBS group fractional shortening ventricular volumes preload recruitable stroke work and end-systolic elastance were all preserved (p < 0 05) in the HG and HG + VEGF groups and further preserved in the HG-VEGF group Conjugated VEGF also produced the highest blood vessel density (p < 0 05) The infarct thinned and dilated after PBS injection but was smaller and thicker in hearts treated with HG (p < 0 05) Our temperature-sensitive HG attenuated adverse cardiac remodeling and improved ventricular function when injected after an MI VEGF delivery enhanced these effects when the VEGF was conjugated to the HG (C) 2010 Elsevier Ltd All rights reserved
引用
收藏
页码:579 / 586
页数:8
相关论文
共 23 条
[1]   Biomaterials for the treatment of myocardial infarction [J].
Christman, Karen L. ;
Lee, Randall J. .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2006, 48 (05) :907-913
[2]   Injectable fibrin scaffold improves cell transplant survival, reduces infarct expansion, and induces neovasculature formation in ischemic myocardium [J].
Christman, KL ;
Vardanian, AJ ;
Fang, QZ ;
Sievers, RE ;
Fok, HH ;
Lee, RJ .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2004, 44 (03) :654-660
[3]   Injectable self-assembling peptide nanofibers create intramyocardial microenvironments for endothelial cells [J].
Davis, ME ;
Motion, JPM ;
Narmoneva, DA ;
Takahashi, T ;
Hakuno, D ;
Kamm, RD ;
Zhang, SG ;
Lee, RT .
CIRCULATION, 2005, 111 (04) :442-450
[4]   Synthesis of protein-polymer conjugates [J].
Heredia, Karina L. ;
Maynard, Heather D. .
ORGANIC & BIOMOLECULAR CHEMISTRY, 2007, 5 (01) :45-53
[5]   Recipient Age determines the cardiac functional improvement achieved by skeletal myoblast transplantation [J].
Kan, Chung-Dann ;
Li, Shu-Hong ;
Weisel, Richard D. ;
Zhang, Shun ;
Li, Ren-Ke .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2007, 50 (11) :1086-1092
[6]   Restraining infarct expansion preserves left ventricular geometry and function after acute anteroapical infarction [J].
Kelley, ST ;
Malekan, R ;
Gorman, JH ;
Jackson, BM ;
Gorman, RC ;
Suzuki, Y ;
Plappert, T ;
Bogen, DK ;
Sutton, MGS ;
Edmunds, LH .
CIRCULATION, 1999, 99 (01) :135-142
[7]   Ionically crosslinked alginate hydrogels as scaffolds for tissue engineering: Part 1. Structure, gelation rate and mechanical properties [J].
Kuo, CK ;
Ma, PX .
BIOMATERIALS, 2001, 22 (06) :511-521
[8]   Enhanced angiogenesis mediated by vascular endothelial growth factor plasmid-loaded thermo-responsive amphiphilic polymer in a rat myocardial infarction model [J].
Kwon, Jin Sook ;
Park, In Kyu ;
Cho, Ae Shin ;
Shin, Sun Mi ;
Hong, Moon Hwa ;
Jeong, Seo Yeon ;
Kim, Yong Sook ;
Min, Jung-Joon ;
Jeong, Myung Ho ;
Kim, Won Jong ;
Jo, Seongbong ;
Pun, Suzie H. ;
Cho, Jeong Gwan ;
Park, Jong Chun ;
Kang, Jung Chaee ;
Ahn, Youngkeun .
JOURNAL OF CONTROLLED RELEASE, 2009, 138 (02) :168-176
[9]   Thermogelling aqueous solutions of alternating multiblock copolymers of poly(L-lactic acid) and poly(ethylene glycol) [J].
Lee, Jisun ;
Bae, You Han ;
Sohn, Youn Soo ;
Jeong, Byeongmoon .
BIOMACROMOLECULES, 2006, 7 (06) :1729-1734
[10]   Cells, scaffolds, and molecules for myocardial tissue engineering [J].
Leor, J ;
Amsalem, Y ;
Cohen, S .
PHARMACOLOGY & THERAPEUTICS, 2005, 105 (02) :151-163