Journal
BIOMATERIALS
Volume 31, Issue 16, Pages 4573-4582Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2010.02.026
Keywords
Affinity-binding; Alginate hydrogel; Angiogenesis; Controlled delivery; Hepatocyte growth factor; Hindlimb ischemia
Funding
- Israel Science Foundation [793/04, 1368/08]
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Enhancing tissue self-repair through the use of active acellular biomaterials is one of the main goals of regenerative medicine. We now describe the features of an injectable alginate biomaterial designed to affinity-bind heparin binding proteins and release them at a rate reflected by their association constant to alginate-sulfate. The interactions of hepatocyte growth factor (HGF) with alginate-sulfate resulted in factor protection from proteolysis, as shown by mass spectroscopy analysis after trypsin digestion. When the HGF/alginate-sulfate bioconjugate was incorporated into alginate hydrogel. HGF release was sustained by a factor of 3, as compared to the release rate from non-modified hydrogel. The released factor retained activity, as shown by its induction of ERK1/2 activation and affording cytoprotection in rat neonatal cardiomyocyte cultures. In vivo, an injectable form of the affinity-binding alginate system extended by 10-fold, as compared to a saline-treated group, retention of HGF in myocardial tissue when delivered immediately after myocardial infarction. In a severe murine hindlimb ischemia model, HGF delivery from the affinity-binding system improved tissue blood perfusion and induced mature blood vessel network formation. The therapeutic efficacy of the affinity-binding system, as well as its ease of delivery by injection, provides a proof-of-concept for the potential use of this bioactive biomaterial strategy in cardiovascular repair. (C) 2010 Elsevier Ltd. All rights reserved.
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