Engineering the heart: Evaluation of conductive nanomaterials for improving implant integration and cardiac function

Abstract

Recently, carbon nanotubes together with other types of conductive materials have been used to enhance the viability and function of cardiomyocytes in vitro. Here we demonstrated a paradigm to construct ECTs for cardiac repair using conductive nanomaterials. Single walled carbon nanotubes (SWNTs) were incorporated into gelatin hydrogel scaffolds to construct three-dimensional ECTs. We found that SWNTs could provide cellular microenvironment in vitro favorable for cardiac contraction and the expression of electrochemical associated proteins. Upon implantation into the infarct hearts in rats, ECTs structurally integrated with the host myocardium, with different types of cells observed to mutually invade into implants and host tissues. The functional measurements showed that SWNTs were essential to improve the performance of ECTs in inhibiting pathological deterioration of myocardium. This work suggested that conductive nanomaterials hold therapeutic potential in engineering cardiac tissues to repair myocardial infarction.

Multifunctional Biomimetic Scaffolds Tailored for Cardiac Regeneration

“…There are several considerations to take into account for fabrication of conductive biomaterials for tissue regeneration of any sort: 204,205 to implantable gelatin/carbon nanotube scaffolds that have helped to increase the functionality of an infarct rat myocardium. 206 Interestingly, an increase in cardiac cell electrical coupling through the gap junction proteins can be seen on the materials without external electrical stimulation. [191][192][193] …”

Nano-Engineered Biomaterials for Tissue Regeneration: What Has Been Achieved So Far?

“…In vivo evidence in mice indicated that therapeutically relevant concentrations of CNTs are non-toxic; thus, there is promise for further in vivo studies with this nanomaterial (Schipper et al, 2008). Lastly, an engineered cardiac tissue consisting of neonatal rat cardiac cells in a gelatin hydrogel with single-walled CNTs (SWNTs) allowed spontaneous contraction and action potentials in vitro in addition to maturation of cardiomyocytes (Zhou et al, 2014). After suturing the graft onto the infarct region in a rat model, with immunosuppression therapy, improved cardiac function 4 weeks post-application and increase in gap junction protein expression was observed (Zhou et al, 2014).…”

“…Metal NPs and carbon nanotubes (CNTs) can increase the conductivity of biomaterial scaffolds (Shin et al, 2013;Shevach et al, 2014;Zhou et al, 2014). ii.…”

“…Lastly, an engineered cardiac tissue consisting of neonatal rat cardiac cells in a gelatin hydrogel with single-walled CNTs (SWNTs) allowed spontaneous contraction and action potentials in vitro in addition to maturation of cardiomyocytes (Zhou et al, 2014). After suturing the graft onto the infarct region in a rat model, with immunosuppression therapy, improved cardiac function 4 weeks post-application and increase in gap junction protein expression was observed (Zhou et al, 2014). It is noted in this study that there was local macrophage upregulation in SWNT-graft treated mice leading to incorporation of SWNTs into the infarct region.…”

“…Peptide NFs can be functionalized with growth factors or stem cell recruitment ligands, such as stromal cell-derived factor 1 (SDF-1) [modified with permission from Davis et al (2005) and Segers et al (2007)]. (iii) Gold nanowires (NW) and carbon nanotubes [such as single-wall nanotubes (SWNTs)] have been incorporated into tissue-engineered cardiac tissue constructs to improve conduction through the scaffold and cardiomyocyte (CM) maturation [modified with permission from Dvir et al (2011) and Zhou et al (2014)]. (iv) Superparamagnetic microspheres (SPM) of iron oxide nanoparticles have been used to reduce post-injection loss ol cardiospherederived cells (CDCs) by using a magnel to target the cell therapy to the infarct region [modified with permission from Cheng et al (2010)].…”