PMC

Scheme showing the mechanism of BIO release within the hydrogel after injection into the MI area.
Abbreviations: BIO, 6-bromoindirubin-3-oxime; IGF-1, insulin-like growth factor 1; MI, myocardial infarction.

In vivo release profile assay.
Notes: (A) The scheme showing the strategy used to monitor the release profile using an in vivo imaging method. (B) Typical images of rats implanted with free Cy7-labeled NPs and Cy7-labeled gelatin NPs encapsulated in hydrogel. (C) The statistical analysis of immunofluorescence intensity remained constant over time (n=6).
Abbreviation: NP, nanoparticle.

Histology evaluation of an ischemic heart.
Notes: (A–E) H&E staining of the tissue sections obtained from the MI region among the (A) sham group, (B) control group, (C) IGF-1 release group, (D) BIO release group, and (E) BIO and IGF-1 co-delivery group. Scale bar, 100 µm.
Abbreviations: BIO, 6-bromoindirubin-3-oxime; IGF-1, insulin-like growth factor 1; H&E, hematoxylin and eosin; MI, myocardial infarction.

Immunostaining for the evaluation of angiogenesis.
Notes: (A–D) CD31 immunostaining of the tissue sections from the MI among the (A) sham group, (B) control group, (C) IGF-1 release group, (D) BIO release group, and (E) BIO and IGF-1 co-delivery group. (F) Statistical analysis of the CD31-positive blood vessels (n=6). *P≤0.05 versus the control group; **P<0.01 versus the control group. The arrows point to the endothelial cells.
Abbreviations: BIO, 6-bromoindirubin-3-oxime; IGF-1, insulin-like growth factor 1; MI, myocardial infarction.

Release assay profile in vitro.
Notes: (A) SEM morphology of the prepared gelatin NPs. (B) DLS analysis of the gelatin NPs. (C) SEM image and a zoomed image showing the gelatin NPs covalently conjugated to the hydrogel. (D) The UV results of BIO absorption showing the release profiles in the free NP group and in the gelatin NP encapsulated in hydrogel group. (E) Mechanical properties of the hydrogel before and after release.
Abbreviations: SEM, scanning electron microscope; DLS, dynamic light scattering; BIO, 6-bromoindirubin-3-oxime; NP, nanoparticle; UV, ultraviolet.

Effect of the hydrogen delivery system on the proliferation of 3D culture cardiomyocytes.
Notes: Scheme showing the strategy used to detect the enhanced proliferation of 3D-cultured cardiomyocytes. Laser confocal images showing the PCNA-positive stained cells in the (A) BgNP group, (B) FgNP group, and (C) OgNP group. (D) Statistical analysis of the number of PCNA-positive cells (n=6). **P<0.01 versus the BgNP group.
Abbreviations: BIO, 6-bromoindirubin-3-oxime; 3D, three dimensional; PCNA, proliferating cell nuclear antigen; NP, nanoparticle; BgNP, blank gelatin nanoparticle; OgNP, BIO-loaded gelatin nanoparticle; IGF-1, insulin-like growth factor 1; FgNP, IGF-1-loaded gelatin nanoparticle.

Double staining with anticardiac troponin-T (green; cardiomyocyte marker) and anti-PCNA (red; proliferation marker) shows the enhanced proliferation of resident cardiomyocytes in an MI model (P<0.01; n=6).
Notes: (A) Sham group, (B) control group, (C) IGF-1 release group, (D) BIO release group, and (E) BIO and IGF-1 co-delivery group. (F) Statistical analysis of the number of double-stained cells. **P<0.01 versus the control group. The arrows show the cardiomyocytes which are double staining.
Abbreviations: BIO, 6-bromoindirubin-3-oxime; IGF-1, insulin-like growth factor 1; MI, myocardial infarction; PCNA, proliferating cell nuclear antigen.