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A novel protein-engineered hepatocyte growth factor analog released via a shear-thinning injectable hydrogel enhances post-infarction ventricular function.
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.
Afiliação
  • Steele AN; Department of Cardiothoracic Surgery, Stanford University, Stanford, California, 94305.
  • Cai L; Department of Bioengineering, Stanford University, Stanford, California, 94305.
  • Truong VN; Department of Materials Science and Engineering, Stanford University, Stanford, California, 94305.
  • Edwards BB; Department of Cardiothoracic Surgery, Stanford University, Stanford, California, 94305.
  • Goldstone AB; Department of Cardiothoracic Surgery, Stanford University, Stanford, California, 94305.
  • Eskandari A; Department of Cardiothoracic Surgery, Stanford University, Stanford, California, 94305.
  • Mitchell AC; Department of Cardiothoracic Surgery, Stanford University, Stanford, California, 94305.
  • Marquardt LM; Department of Bioengineering, Stanford University, Stanford, California, 94305.
  • Foster AA; Department of Materials Science and Engineering, Stanford University, Stanford, California, 94305.
  • Cochran JR; Department of Materials Science and Engineering, Stanford University, Stanford, California, 94305.
  • Heilshorn SC; Department of Bioengineering, Stanford University, Stanford, California, 94305.
  • Woo YJ; Department of Bioengineering, Stanford University, Stanford, California, 94305.
Biotechnol Bioeng ; 114(10): 2379-2389, 2017 10.
Article em En | MEDLINE | ID: mdl-28574594
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Recombinantes / Engenharia de Proteínas / Fator de Crescimento de Hepatócito / Disfunção Ventricular Esquerda / Hidrogéis / Preparações de Ação Retardada / Infarto do Miocárdio Limite: Animals Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Recombinantes / Engenharia de Proteínas / Fator de Crescimento de Hepatócito / Disfunção Ventricular Esquerda / Hidrogéis / Preparações de Ação Retardada / Infarto do Miocárdio Limite: Animals Idioma: En Ano de publicação: 2017 Tipo de documento: Article