Development of Bioactive Patch for Maintenance of Implanted Cells at the Myocardial Infarcted Site

Abstract

Ischemia produced as a result of myocardial infarction might cause moderate or severe tissue death. Studies under development propose grafting stem cells into the affected area and we hypothesize that this mechanism could be enhanced by the application of a "bioactive implant. " The implant herein proposed consists of a thin porous elastomeric membrane, filled with self-assembling nanofibers and human subcutaneous adipose tissue derived progenitor cells. We describe the development and characterization of two elastomeric membranes: poly(ethyl acrylate) (PEA) and poly(caprolactone 2-(methacryloyloxy)ethyl ester) (PCLMA). Both are a good material support to deliver cells within a soft self-assembling peptide and are elastic enough to withstand the stresses arising from the heartbeat. Both developed composites (PEA and PCLMA, combined with self-assembling peptide) equally facilitate the propagation of electrical pulses and maintain their genetic profile of the seeded cells. Preliminary studies with small animal models suggest that, at short times, the bioimplant shows good adhesion with the myocardium. After three days cells loaded in the patch remain alive at the implanted site. We propose that the bioactive patch (elastomeric membranes with self-assembling peptide and cells) could increase the efficacy of future cardiac cell therapy by improving cell immobilization and survival at the affected site.

Scaffolds and tissue regeneration: An overview of the functional properties of selected organic tissues

“…The results were promising, and the contractile cardiac function was detected by echocardiography after 4 weeks of implantation of the scaffold. 104 …”

Topologically controlled hyaluronan-based gel coatings of hydrophobic grid-like scaffolds to modulate drug delivery

“…Among them, poly(ethyl acrylate) (PEA) is a biostable polymer with good biocompatibility with cells such as chondrocytes [1], osteoblasts [2], endothelial cells [3], keratinocytes [4], neural cells [5][6][7][8] or dental pulp stem cells [9], and has been proposed as a feeder-free platform for the maintenance and growth of embryonic stem cells [10]. Its scaffolds have been implanted in several tissues with regenerative purposes [5,[11][12][13]. They can be manufactured in a variety of pore architectures including aligned [14] and interwoven [15] microchannels and interconnected microspheres [16] by using porogen leaching techniques.…”

“…It's density is 1.13 gcm -3 [18]. Additionally, PEA is a hydrophobic polymer and the amorphous networks thereof result in low water uptake (equilibrium water content in PBS of 1.14±0.16% [13]), thus maintaining their size and shape stable in aqueous environments. PEA has been shown to favor the adhesion of proteins such as fibronectin [2,19] and to induce its spontaneous fibrillogenesis, due to the particular mobility and polarity of its side chain, together with its low wettability.…”

Hydrophilic surface modification of acrylate-based biomaterials

“…In particular, the presence of acid groups improves wettability, which can facilitate the seeding of porous materials [15], but also the presence of surface charges are reported to affect the deposition of ECM-proteins [16][17][18] that would translate into a better cell-material interaction or differentiation for certain cell lines [5,19,20]. Indeed, the preconditioning of hydrophobic PEA scaffolds with a hydrogel has been found to improve significantly cell seeding and migration to colonize them homogeneously [21][22][23].…”