TY - JOUR
T1 - Hyaluronic acid-human blood hydrogels for stem cell transplantation
AU - Chang, Connie Y.
AU - Chan, Angel T.
AU - Armstrong, Patrick A.
AU - Luo, Hong Chang
AU - Higuchi, Takahiro
AU - Strehin, Iossif A.
AU - Vakrou, Styliani
AU - Lin, Xiaoping
AU - Brown, Sophia N.
AU - O'Rourke, Brian
AU - Abraham, Theodore P.
AU - Wahl, Richard L.
AU - Steenbergen, Charles J.
AU - Elisseeff, Jennifer H.
AU - Abraham, M. Roselle
N1 - Funding Information:
This work was funded by the American heart association (AHA-BGIA) , NIH RO1 HL092985 and NIH 5UL1RR025005-05 . Dr. Angel Chan was supported by NIH T32HL07227 Training Grant. Dr. Stella Vakrou was supported by Hellenic Society of Cardiology . Sophia Brown, MS was supported by a NIH Diversity supplement to RO1 HL092985 . Dr. Xiaoping Lin was partially supported by the China Scholarship Council . We are grateful to James Fox and Jim Engles for technical assistance.
PY - 2012/11
Y1 - 2012/11
N2 - 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 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.
AB - 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 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.
KW - Autologous blood hydrogel
KW - Bioadhesive and biodegradable hydrogel
KW - Cardiac stem cell transplantation
KW - Echocardiography
KW - Modified hyaluronic acid
KW - Molecular imaging
UR - https://www.scopus.com/pages/publications/84865562550
U2 - 10.1016/j.biomaterials.2012.07.058
DO - 10.1016/j.biomaterials.2012.07.058
M3 - Article
C2 - 22898181
AN - SCOPUS:84865562550
SN - 0142-9612
VL - 33
SP - 8026
EP - 8033
JO - Biomaterials
JF - Biomaterials
IS - 32
ER -