Injectable Self-Assembling Peptide Nanofibers Create Intramyocardial Microenvironments for Endothelial Cells

Abstract

Background-Promoting survival of transplanted cells or endogenous precursors is an important goal. We hypothesized that a novel approach to promote vascularization would be to create injectable microenvironments within the myocardium that recruit endothelial cells and promote their survival and organization. Methods and Results-In this study we demonstrate that self-assembling peptides can be injected and that the resulting nanofiber microenvironments are readily detectable within the myocardium. Furthermore, the self-assembling peptide nanofiber microenvironments recruit progenitor cells that express endothelial markers, as determined by staining with isolectin and for the endothelial-specific protein platelet-endothelial cell adhesion molecule-1. Vascular smooth muscle cells are recruited to the microenvironment and appear to form functional vascular structures. After the endothelial cell population, cells that express ␣-sarcomeric actin and the transcription factor Nkx2.5 infiltrate the peptide microenvironment. When exogenous donor green fluorescent protein-positive neonatal cardiomyocytes were injected with the self-assembling peptides, transplanted cardiomyocytes in the peptide microenvironment survived and also augmented endogenous cell recruitment. Conclusions-These experiments demonstrate that self-assembling peptides can create nanofiber microenvironments in the myocardium and that these microenvironments promote vascular cell recruitment. Because these peptide nanofibers may be modified in a variety of ways, this approach may enable injectable tissue regeneration strategies.

Local myocardial insulin-like growth factor 1 (IGF-1) delivery with biotinylated peptide nanofibers improves cell therapy for myocardial infarction

“…Cardiomyocytes from 1-day-old Sprague-Dawley pups (Charles River Laboratories) were obtained as described in ref. 12. The resulting cell pellet was resuspended in sucrose or self-assembling peptides for in vitro and in vivo studies.…”

“…On exposure to physiological osmolarity and pH, the peptides rapidly assemble into small nanofibers (Ϸ10 nm) that can be injected into the myocardium to form 3D cellular microenvironments (11,12). These peptide nanofiber microenvironments recruit a variety of cells including vascular cells (12).…”

Polymeric Nanofibers in Tissue Engineering

“…2,8,54,55 Further, this approach could be used to assemble the nanofibers in vivo to create an injectable scaffold for tissue repair 56 ; however, competition with natural amphiphiles present in vivo could complicate this application. While this approach creates nanofibers of the smallest scale (5-8 nm), the fabrication process is a challenging technique, limited to a few polymers, and can only create short fibers with lengths of one to several mm.…”

Heart regeneration after myocardial infarction using synthetic biomaterials

“…et al demonstrated that RADA16-II peptides rapidly gel when mixed with sterile sucrose solution. The resulting hydrogel created a microenvironment in the myocardium which promoted vascular cell recruitment and favored injected cell survival [63]. Then, Lin Y.D.…”