Hyaluronic acid-human blood hydrogels for stem cell transplantation.
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±12 s, 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 4 wks 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.
Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Connie Y
CY
Chang
Angel T
AT
Chan
Patrick A
PA
Armstrong
Hong-Chang
HC
Luo
Takahiro
T
Higuchi
Iossif A
IA
Strehin
Styliani
S
Vakrou
Xiaoping
X
Lin
Sophia N
SN
Brown
Brian
B
O'Rourke
Theodore P
TP
Abraham
Richard L
RL
Wahl
Charles J
CJ
Steenbergen
Jennifer H
JH
Elisseeff
M Roselle
MR
Abraham
D000818:Animals; D001773:Blood Cells / Q000737:chemistry* / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D055119:Elastic Modulus; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000378:metabolism; D020100:Hydrogels / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000601:surgery; D009206:Myocardium / Q000166:cytology* / Q000473:pathology; D010949:Plasma / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D011923:Rats, Nude; D033581:Stem Cell Transplantation; D013388:Succinimides / Q000737:chemistry; D054457:Tissue Scaffolds / Q000737:chemistry*
D020100:Hydrogels; D013388:Succinimides; D006820:Hyaluronic Acid; C001426:N-hydroxysuccinimide