Hyaluronic acid-human blood hydrogels for stem cell transplantation

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

Research output: Contribution to journalArticle

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 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.

Original languageEnglish (US)
Pages (from-to)8026-8033
Number of pages8
JournalBiomaterials
Volume33
Issue number32
DOIs
StatePublished - Nov 1 2012

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Keywords

  • Autologous blood hydrogel
  • Bioadhesive and biodegradable hydrogel
  • Cardiac stem cell transplantation
  • Echocardiography
  • Modified hyaluronic acid
  • Molecular imaging

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Chang, C. Y., Chan, A. T., Armstrong, P. A., Luo, H. C., Higuchi, T., Strehin, I. A., Vakrou, S., Lin, X., Brown, S. N., O'Rourke, B., Abraham, T. P., Wahl, R. L., Steenbergen, C. J., Elisseeff, J. H., & Abraham, M. R. (2012). Hyaluronic acid-human blood hydrogels for stem cell transplantation. Biomaterials, 33(32), 8026-8033. https://doi.org/10.1016/j.biomaterials.2012.07.058