Hyaluronic acid-human blood hydrogels for stem cell transplantation.

Abstract

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.

• Authors: Connie Y Chang, Angel T Chan, Patrick A Armstrong, Hong-Chang Luo, Takahiro Higuchi, Iossif A Strehin, Styliani Vakrou, Xiaoping Lin, Sophia N Brown, Brian O'Rourke, Theodore P Abraham, Richard L Wahl, Charles J Steenbergen, Jennifer H Elisseeff, M Roselle Abraham
• Journal: Biomaterials (Biomaterials) Vol. 33 Issue 32 Pg. 8026-33 (Nov 2012) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 22898181 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Published by Elsevier Ltd.

Chemical References

• Hydrogels
• Succinimides
• Hyaluronic Acid
• N-hydroxysuccinimide

Topics

• Animals
• Blood Cells (chemistry, metabolism)
• Cell Proliferation
• Cell Survival
• Cells, Cultured
• Elastic Modulus
• Female
• Humans
• Hyaluronic Acid (chemistry, metabolism)
• Hydrogels (chemistry, metabolism)
• Male
• Myocardial Infarction (pathology, surgery)
• Myocardium (cytology, pathology)
• Plasma (chemistry, metabolism)
• Rats
• Rats, Inbred WKY
• Rats, Nude
• Stem Cell Transplantation
• Succinimides (chemistry)
• Tissue Scaffolds (chemistry)