Delivery of rPN/Gelfoam system increased vascularization in the border zone.

<p>(A, B) Visualization of CD31 positive vessels within the border zone in both control (A) and rPN (B) treated animals. (C) Quantification of vessel density in the border zone. Ctr, hearts receiving Gelfoam with PBS; rPN, hearts receiving Gelfoam with periostin peptide; <i>n</i> is the number of animals per group. Scale bars, 100 µm.</p

Fibrin encased Gelfoam hydrogels prolong rPN release In Vitro and In Vivo.

<p>(A) <i>In vitro</i> release kinetics of fluorescently-labeled rPN (rPN-AF488) from Gelfoam and Gelfoam-Fibrin composite hydrogels in PBS at 4°C. (B) <i>In vivo</i> release kinetics of rPN-AF488 from Gelfoam and Gelfoam/Heparin hydrogels implanted within the peritoneal cavity of mice. (C) Gelfoam sponges loaded with rPN –AF488 were explanted and characterized by immunohistochemistry and immunofluorescence. Sections were stained with hemotoxylin and eosin (H&E), fibrin(ogen), and acid fuschin orange –G (AFOG). Green arrows indicate fibrin deposition within the Gelfoam sponge. Scale bars, 50 µm.</p

Gelfoam gels loaded with rPN become encased with fibrin-rich hydrogels after intrapericardial injection in pigs.

<p>(A) Cross-sectional photomicrograph of the explanted Gelfoam disk 7 days after implantation. (B–D) Explanted Gelfoam disks were characterize d with hematoxylin and eosin (H&E, B), immunofluorescent staining for fibrinogen (C) acid-fuschin orange-G (AFOG, D). Green arrows indicate fibrin deposition. Scale bars, (A) 20 mm; (B–D) 50 µm.</p

Gelfoam loaded with rPN increases cardiomyocyte cell cycle activity after MI.

<p>(A–D) Visualization and quantification of cell cycle activity in tissue sections and in isolated cardiomyocytes from animals treated with rPN, respectively. (E–F) Determination of cardiomyocyte mitosis by visualization of H3P positive cardiomyocyte nuclei. A series of yz reconstructions is shown to the right of the micrograph. (G) Quantification of cardiomyocyte mitosis after 1 wk and 12 wks of treatment. (H) Quantification of the effect of administering rPN adsorbed onto Gelfoam versus administration of rPN alone on cardiomyocyte mitosis. H3P, phosphorylated histone H3 (S10); Ctr, hearts receiving Gelfoam with PBS; rPN, hearts receiving Gelfoam with periostin peptide; <i>n</i> is the number of animals per group. Scale bars, 100 µm.</p

rPN readily diffuses into damaged myocardium.

<p>(A–B) Cross-sectional photomicrographs and pixel intensity profiles of rPN-AF488 diffusion through non-infarcted (A) and infarcted (B) mouse hearts. (C) Photomicrograph and pixel intensity prolife for cryo-injured heart only. (D) Quantification reveals that rPN readily diffuses through injured myocardium but not healthy intact muscle. Red arrows demarcate the epicardial surface and white arrows represent Gelfoam loaded with rPN-AF488. Analysis was performed 2 hrs after cryo-injury. The mean ± SEM of 6 independent pixel intensity profiles is provided in the graphs.</p

Release Rates.

<p>In Vitro and In Vivo release rates from Gelfoam hydrogels.</p

Gelfoam hydrogels explanted from the peritoneal cavity of mice are encased within a fibrin matrix.

<p>(A) Photomicrographs of explanted Gelfoam sponges at various time points. (B) Explanted Gelfoam sponges were characterized by immunohistochemistry and immunofluorescence. Sections were stained with hemotoxylin and eosin (H&E), fibrin(ogen), and acid fuschin orange –G (AFOG). Green arrows indicate fibrin deposition within the Gelfoam sponge. Scale bars, (A) 10 mm; (B) 50 µm.</p

Myocardial infarction timeline and strategy for targeted delivery.

<p>(A) Experimental design for the delivery of rPN in a swine model of myocardial infarction (MI). (B) Schematic illustration of the intrapericardial delivery of Gelfoam/rPN system and our strategy for tissue collection.</p

Administration of rNRG1 during the somatic growth phase does not induce neoplastic growth in the head and abdomen.

<p>Mice received daily BSA or rNRG1 injections between day of life 0 and 35. Representative examples of sagittal (A, left panels), coronal (A, right panels) MRI scans of brain, and abdomen (B) for a BSA and rNRG1-treated mice on day of life 35 are shown.</p

Diagrams of study design.

<p>Daily injections of vehicle (BSA) and rNRG1 were begun on the day of life 0 (A, B) and day of life 5 (C) and are indicated with red boxes. Cryoinjury was performed on day of life 1 (P1, B, C). DOL, day of life.</p