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

Abstract

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.

Video abstract

Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use:

http://youtu.be/BFm9vZm17C4

Keywords:

• myocardial infarction
• gelatin nanoparticle
• cardiomyocyte proliferation
• injectable hydrogel

Acknowledgments

This research is supported by the National Natural Science Foundation of China (grant 81361128005), the Fundamental Research Funds for the Central Universities (grant HIT. IBRSEM. 201334), the Opening Foundation of the State Key Laboratory of Cancer Biology (grant CBSKL201106), and the Opening Foundation of the State Key Laboratory of Space Medicine (grant SFA10K02). English language editing of this manuscript was provided by Journal Prep (Montreal, Quebec, Canada).

Disclosure

The authors report no conflicts of interest in this work.