Drug and cell delivery for cardiac regeneration

Abstract

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.

Heart regeneration after myocardial infarction using synthetic biomaterials

“…Focusing on myocardial regeneration, it requires the administration of multipotent cells able to differentiate into the main cardiac cell lineages myocytes, vascular smooth muscle cells and endothelial cells [16] and to develop both CMCs and coronary vessels [17]. To date, the most popular cell candidates used to regenerate the damaged tissue include adipose derived stem cells (ADSCs), mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), endothelial progenitor cells (EPCs), bone marrow derived stem cells (BMSCs), induced pluripotent stem cells (iPS), cardiac progenitor cells (CPCs) and induced cardiomyocytes (iCMs) [18]. However, although several SCs have been tested in in vitro and in vivo preclinical studies with promising results [19], not too many SCs have reached clinical trials.…”

Hydrogels for Cardiac Tissue Repair and Regeneration

“…In comparison with the control (cells without collagen matrix) it was reported that the retention of transplanted cells in the target tissue was done for a long time [26]. Also, it was reported that a collagen patch has been successfully used like a delivery vehicle for human mesenchymal stem cells and human embryonic stem cell derived mesenchymal cells for cardiac repair [27].…”

Biomaterial‐Enhanced Cell and Drug Delivery: Lessons Learned in the Cardiac Field and Future Perspectives

“…(76) Injectable hydrogels can be used as a surrogate ECM for encapsulated cells, demonstrated that delivering skeletal myoblasts in an injectable fibrin hydrogel to infarcted rat hearts increased cell retention and survival with improved functional outcomes. (57) Since then a variety of materials and cell types have been utilised to improve cell retention over saline controls (table 1).…”

“…However, the main downfall of this approach is difficulties in retaining the cells and therapeutic at the target site. (131)(132)(133) Despite these challenges, there has been some progress in the catheter delivery of biomaterials alone whereby several pre-clinical studies have determined the feasibility using commercially available catheters. (34,79,134,135) The challenge to date remains in combining these two approaches to develop a minimally invasive delivery strategy for advanced biomaterials, which incorporates cells .…”

“…Until now the preclinical trials have been performed using sternotomy which is an open chest procedure and is used as an approach for open heart procedures. (136,137) It's complications may include sternal wound infection and dehiscence, dysrhythmias, haemorrhage, sternal instability and pseudoarthrosis, keloid and hypertrophic scars. Mechanical assist devices could be an option for delivering biomaterials.…”