A novel protein‐engineered hepatocyte growth factor analog released via a shear‐thinning injectable hydrogel enhances post‐infarction ventricular function

ABSTRACT In the last decade, numerous growth factors and biomaterials have been explored for the treatment of myocardial infarction (MI). While pre‐clinical studies have demonstrated promising results, clinical trials have been disappointing and inconsistent, likely due to poor translatability. In t...

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Published in:Biotechnology and bioengineering 2017-10, Vol.114 (10), p.2379-2389
Main Authors: Steele, Amanda N., Cai, Lei, Truong, Vi N., Edwards, Bryan B., Goldstone, Andrew B., Eskandari, Anahita, Mitchell, Aaron C., Marquardt, Laura M., Foster, Abbygail A., Cochran, Jennifer R., Heilshorn, Sarah C., Woo, Y. Joseph
Format: Article
Language:English
Subjects:
Angiogenesis
Angiogenic Proteins - administration & dosage
Angiogenic Proteins - chemistry
Angiogenic Proteins - genetics
Animals
Bioengineering
Biomaterials
Biomedical materials
Clinical trials
Delayed-Action Preparations - administration & dosage
Delayed-Action Preparations - chemistry
Diffusion
Encapsulation
Fibrosis
growth factor
Growth factors
Healing
Hepatocyte growth factor
Hepatocyte Growth Factor - administration & dosage
Hepatocyte Growth Factor - analogs & derivatives
Hepatocyte Growth Factor - genetics
hydrogel
Hydrogels
Hydrogels - chemistry
Injections
Male
Medical research
Myocardial infarction
Myocardial Infarction - diagnostic imaging
Myocardial Infarction - drug therapy
Myocardial Infarction - pathology
myocardial regeneration
Phosphates
Protein Engineering - methods
Proteins
Rats
Rats, Sprague-Dawley
Rats, Wistar
Recombinant Proteins - administration & dosage
Recombinant Proteins - chemistry
Recombinant Proteins - genetics
Rodents
Shear Strength
Surgery
Surgical implants
Thinning
Treatment Outcome
Ventricle
Ventricular Dysfunction, Left - diagnostic imaging
Ventricular Dysfunction, Left - pathology
Ventricular Dysfunction, Left - prevention & control
Viscosity
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Summary:ABSTRACT In the last decade, numerous growth factors and biomaterials have been explored for the treatment of myocardial infarction (MI). While pre‐clinical studies have demonstrated promising results, clinical trials have been disappointing and inconsistent, likely due to poor translatability. In the present study, we investigate a potential myocardial regenerative therapy consisting of a protein‐engineered dimeric fragment of hepatocyte growth factor (HGFdf) encapsulated in a shear‐thinning, self‐healing, bioengineered hydrogel (SHIELD). We hypothesized that SHIELD would facilitate targeted, sustained intramyocardial delivery of HGFdf thereby attenuating myocardial injury and post‐infarction remodeling. Adult male Wistar rats (n = 45) underwent sham surgery or induction of MI followed by injection of phosphate buffered saline (PBS), 10 μg HGFdf alone, SHIELD alone, or SHIELD encapsulating 10 μg HGFdf. Ventricular function, infarct size, and angiogenic response were assessed 4 weeks post‐infarction. Treatment with SHIELD + HGFdf significantly reduced infarct size and increased both ejection fraction and borderzone arteriole density compared to the controls. Thus, sustained delivery of HGFdf via SHIELD limits post‐infarction adverse ventricular remodeling by increasing angiogenesis and reducing fibrosis. Encapsulation of HGFdf in SHIELD improves clinical translatability by enabling minimally‐invasive delivery and subsequent retention and sustained administration of this novel, potent angiogenic protein analog. Biotechnol. Bioeng. 2017;114: 2379–2389. © 2017 Wiley Periodicals, Inc. Masson's Trichrome staining of a rat heart section. Treatment with a novel bioengineered hepatocyte growth factor delivered via a shear‐thinning hydrogel reduces infarct size in a rodent model of myocardial infarction.
ISSN:0006-3592
1097-0290
DOI:10.1002/bit.26345