Implantation of a Poly-L-Lactide GCSF-Functionalized Scaffold in a Model of Chronic Myocardial Infarction

J Cardiovasc Transl Res. 2017 Feb;10(1):47-65. doi: 10.1007/s12265-016-9718-9. Epub 2017 Jan 23.

Abstract

A previously developed poly-L-lactide scaffold releasing granulocyte colony-stimulating factor (PLLA/GCSF) was tested in a rabbit chronic model of myocardial infarction (MI) as a ventricular patch. Control groups were constituted by healthy, chronic MI and nonfunctionalized PLLA scaffold. PLLA-based electrospun scaffold efficiently integrated into a chronic infarcted myocardium. Functionalization of the biopolymer with GCSF led to increased fibroblast-like vimentin-positive cellular colonization and reduced inflammatory cell infiltration within the micrometric fiber mesh in comparison to nonfunctionalized scaffold; PLLA/GCSF polymer induced an angiogenetic process with a statistically significant increase in the number of neovessels compared to the nonfunctionalized scaffold; PLLA/GCSF implanted at the infarcted zone induced a reorganization of the ECM architecture leading to connective tissue deposition and scar remodeling. These findings were coupled with a reduction in end-systolic and end-diastolic volumes, indicating a preventive effect of the scaffold on ventricular dilation, and an improvement in cardiac performance.

Keywords: 3D scaffold; Cardiac graft; Electrospinning; GCSF; Myocardial infarction; PLLA; Tissue engineering.

MeSH terms

  • Animals
  • Chronic Disease
  • Computed Tomography Angiography
  • Disease Models, Animal
  • Drug Carriers*
  • Drug Compounding
  • Echocardiography
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism
  • Extracellular Matrix / pathology
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Filgrastim / administration & dosage*
  • Filgrastim / chemistry
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardium* / metabolism
  • Myocardium* / pathology
  • Neovascularization, Physiologic / drug effects
  • Polyesters / chemistry*
  • Rabbits
  • Recovery of Function
  • Time Factors
  • Ventricular Function, Left / drug effects
  • Ventricular Remodeling / drug effects
  • Vimentin / metabolism

Substances

  • Drug Carriers
  • Polyesters
  • Vimentin
  • poly(lactide)
  • Filgrastim