Hyaluronic acid-human blood hydrogels for stem cell transplantation

Biomaterials. 2012 Nov;33(32):8026-33. doi: 10.1016/j.biomaterials.2012.07.058. Epub 2012 Aug 13.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Hydrogels
  • Succinimides
  • Hyaluronic Acid
  • N-hydroxysuccinimide