The spectrum of ischaemic cardiomyopathy, encompassing acute myocardial infarction to congestive heart failure is a significant clinical issue in the modern era. This group of diseases is an enormous source of morbidity and mortality and underlies significant healthcare costs worldwide. Cardiac regenerative therapy, whereby pro-regenerative cells, drugs or growth factors are administered to damaged and ischaemic myocardium has demonstrated significant potential, especially preclinically. While some of these strategies have demonstrated a measure of success in clinical trials, tangible clinical translation has been slow. To date, the majority of clinical studies and a significant number of preclinical studies have utilised relatively simple delivery methods for regenerative therapeutics, such as simple systemic administration or local injection in saline carrier vehicles. Here, we review cardiac regenerative strategies with a particular focus on advanced delivery concepts as a potential means to enhance treatment efficacy and tolerability and ultimately, clinical translation. These include (i) delivery of therapeutic agents in biomaterial carriers, (ii) nanoparticulate encapsulation, (iii) multimodal therapeutic strategies and (iv) localised, minimally invasive delivery via percutaneous transcatheter systems.

Cell delivery to the infarcted heart has emerged as a promising therapy, but is limited by very low acute retention and engraftment of cells. The objective of the study was to compare a panel of biomaterials to evaluate if acute retention can be improved with a biomaterial carrier. Cells were quantified post-implantation in a rat myocardial infarct model in five groups (n=7–8); saline injection (current clinical standard), two injectable hydrogels (alginate, chitosan/β-glycerophosphate) and two epicardial patches (alginate, collagen). Human mesenchymal stem cells (hMSCs) were delivered to the infarct border zone with each biomaterial. At 24 hours, retained cells were quantified by fluorescence. All biomaterials had superior fluorescence to saline control, with 8 and 14-fold increases with alginate and chitosan/β-GP injectables, and 47 and 59-fold increases achieved with collagen and alginate patches, respectively. Immunohistochemical analysis qualitatively confirmed these findings. All four biomaterials retained 50–60% of cells that were present immediately following transplantation, compared to 10% for the saline control. In conclusion, all four injectable hydrogels and epicardial patches were demonstrated to more efficiently deliver and retain cells when compared to a saline control. Biomaterial-based delivery approaches show promise for future development of efficient in vivo delivery techniques.