Hyaluronic acid-human blood hydrogels for stem cell transplantation

被引:49
作者
Chang, Connie Y. [2 ]
Chan, Angel T. [1 ]
Armstrong, Patrick A. [2 ]
Luo, Hong-Chang [1 ]
Higuchi, Takahiro [3 ]
Strehin, Iossif A. [2 ]
Vakrou, Styliani [1 ]
Lin, Xiaoping [1 ]
Brown, Sophia N. [1 ]
O'Rourke, Brian [1 ]
Abraham, Theodore P. [1 ]
Wahl, Richard L. [3 ]
Steenbergen, Charles J. [4 ]
Elisseeff, Jennifer H. [2 ]
Abraham, M. Roselle [1 ]
机构
[1] Johns Hopkins Sch Med, Div Cardiovasc Med, Baltimore, MD 21205 USA
[2] Johns Hopkins Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA
[3] Johns Hopkins Sch Med, Dept Radiol, Baltimore, MD 21205 USA
[4] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD 21205 USA
关键词
Bioadhesive and biodegradable hydrogel; Autologous blood hydrogel; Modified hyaluronic acid; Cardiac stem cell transplantation; Molecular imaging; Echocardiography; HEART; ANGIOGENESIS; IMPLANTATION; MYOCARDIUM; SCAFFOLD;
D O I
10.1016/j.biomaterials.2012.07.058
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Tissue engineering-based approaches have the potential to improve stem cell engraftment by increasing cell delivery to the myocardium. Our objective was to develop and characterize a naturally-derived, autologous, biodegradable hydrogel in order to improve acute stem cell retention in the myocardium. HA-blood hydrogels (HA-BL) were synthesized by mixing in a 1:1(v/v) ratio, lysed whole blood and hyaluronic acid (HA), whose carboxyl groups were functionalized with N-hydroxysuccinimide (NHS) to yield HA succinimidyl succinate (HA NHS). We performed physical characterization and measured survival/proliferation of cardiosphere-derived cells (CDCs) encapsulated in the hydrogels. Hydrogels were injected intra-myocardially or applied epicardially in rats. NHS-activated carboxyl groups in HA react with primary amines present in blood and myocardium to form amide bonds, resulting in a 3D hydrogel bound to tissue. HA-blood hydrogels had a gelation time of 58 +/- 12s, swelling ratio of 10 +/- 0.5, compressive and elastic modulus of 14 +/- 3 and 1.75 +/- 0.6 kPa respectively. These hydrogels were not degraded at 4wks by hydrolysis alone. CDC encapsulation promoted their survival and proliferation. Intra-myocardial injection of CDCs encapsulated in these hydrogels greatly increased acute myocardial retention (p = 0.001). Epicardial application of HA-blood hydrogels improved left ventricular ejection fraction following myocardial infarction (p = 0.01). HA-blood hydrogels are highly adhesive, biodegradable, promote CDC survival and increase cardiac function following epicardial application after myocardial infarction. Published by Elsevier Ltd.
引用
收藏
页码:8026 / 8033
页数:8
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