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

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.

Mussel-inspired conductive nanofibrous membranes repair myocardial infarction by enhancing cardiac function and revascularization

“…Reinforced electrical conduction in scaffolds is beneficial to CM function and synchronous contraction 7 , 63 , 64 . Our results also suggest that the dopa-based conductive membranes are better for the formation of sarcomeres in CMs.…”

“…Engineered cardiac patches (ECP), which consist of seeding cells and scaffolds, provide promising strategies for infarcted myocardium regeneration 1 - 3 . Biomimetic microenvironments consisting of ECP can promote cardiomyocyte (CM) function and yield synchronous contraction in vitro 4 - 7 . They can also repair myocardial infarction and enhance cardiac function in vivo 6 , 8 .…”

A review: Nanofibrous scaffold in possible prevention and treatment of coronary artery disease

“…They also reported neovascularization, decreased fibrosis, positive remodeling, and improved left ventricular function compared with controls . Composite of PLLA and GCF for the repair of myocardium is seen effective to induce vascularization and tissue healing . In a recent study, polypyrrole and methyl acrylic anhydride‐gelatin nanoparticles were cross‐linked on PCL membrane using mussel crosslinker to generate cardiac patch.…”

Biodegradable polymers suitable for tissue engineering and drug delivery systems

“…Spadaccio et al have demonstrated that functionalization of the PLLA biopolymer with granulocyte colony-stimulating factor (GCSF), tested as a ventricular patch in a rabbit chronic model of myocardial infarction, induced an angiogenetic process with a significant increase in the number of new vessels compared to the nonfunctionalized scaffold [58].…”