Sustained co-delivery of BIO and IGF-1 by a novel hybrid hydrogel system to stimulate endogenous cardiac repair in myocardial infarcted rat hearts

Int J Nanomedicine. 2015 Jul 28:10:4691-703. doi: 10.2147/IJN.S81451. eCollection 2015.


Dedifferentiation and proliferation of endogenous cardiomyocytes in situ can effectively improve cardiac repair following myocardial infarction (MI). 6-Bromoindirubin-3-oxime (BIO) and insulin-like growth factor 1 (IGF-1) are two potent factors that promote cardiomyocyte survival and proliferation. However, their delivery for sustained release in MI-affected areas has proved to be challenging. In the current research, we present a study on the sustained co-delivery of BIO and IGF-1 in a hybrid hydrogel system to simulate endogenous cardiac repair in an MI rat model. Both BIO and IGF-1 were efficiently encapsulated in gelatin nanoparticles, which were later cross-linked with the oxidized alginate to form a novel hybrid hydrogel system. The in vivo results indicated that the hybrid system could enhance the proliferation of cardiomyocytes in situ and could promote revascularization around the MI sites, allowing improved cardiac function. Taken together, we concluded that the hybrid hydrogel system can co-deliver BIO and IGF-1 to areas of MI and thus improve cardiac function by promoting the proliferation of cardiomyocytes and revascularization.

Keywords: cardiomyocyte proliferation; gelatin nanoparticle; injectable hydrogel; myocardial infarction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Carriers* / chemistry
  • Drug Carriers* / pharmacokinetics
  • Drug Carriers* / pharmacology
  • Hydrogel, Polyethylene Glycol Dimethacrylate* / chemistry
  • Hydrogel, Polyethylene Glycol Dimethacrylate* / pharmacokinetics
  • Hydrogel, Polyethylene Glycol Dimethacrylate* / pharmacology
  • Indoles* / chemistry
  • Indoles* / pharmacokinetics
  • Indoles* / pharmacology
  • Insulin-Like Growth Factor I* / chemistry
  • Insulin-Like Growth Factor I* / pharmacokinetics
  • Insulin-Like Growth Factor I* / pharmacology
  • Myocardial Infarction / metabolism*
  • Myocytes, Cardiac / metabolism*
  • Oximes* / chemistry
  • Oximes* / pharmacokinetics
  • Oximes* / pharmacology
  • Rats
  • Regeneration


  • 6-bromoindirubin-3'-oxime
  • Drug Carriers
  • Indoles
  • Oximes
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Insulin-Like Growth Factor I