Targeted Myocardial Restoration with Injectable Hydrogels-In Search of The Holy Grail in Regenerating Damaged Heart Tissue

Abstract

A 3-dimensional, robust, and sustained myocardial restoration by means of tissue engineering remains an experimental approach. Prolific protocols have been developed and tested in small and large animals, but, as clinical cardiac surgeons, we have not arrived at the privilege of utilizing any of them in our clinical practice. The question arises as to why this is. The heart is a unique organ, anatomically and functionally. It is not an easy target to replicate with current techniques, or even to support in its viability and function. Currently, available therapies fail to reverse the loss of functional cardiac tissue, the fundamental pathology remains unaddressed, and heart transplantation is an ultima ratio treatment option. Owing to the equivocal results of cell-based therapies, several strategies have been pursued to overcome the limitations of the current treatment options. Preclinical data, as well as first-in-human studies, conducted to-date have provided important insights into the understanding of injection-based approaches for myocardial restoration. In light of the available data, injectable biomaterials suitable for transcatheter delivery appear to have the highest translational potential. This article presents a current state-of-the-literature review in the field of hydrogel-based myocardial restoration therapy.

Keywords: cardiac stem cell therapy; cell-based therapy; extracellular matrix hydrogels; hydrogel; myocardial infarction therapy; myocardial infarctions; tissue engineering.

Figure 1

Vicious circle of myocardial ischemia and ventricular wall remodeling after MI. EF: ejection fraction. (A): representative diagram of the vicious circle of myocardial ischemia, kickstarted by an initial myocardial infarction. (B): contraction of the LV in a healthy heart and the EF produced as a result of efficient contraction. (C): contraction of a post-MI heart and the reduced EF produced as a result of altered cardiac architecture.

Figure 2

Diagram showing the current methods of regenerative cardiac therapy. (A): Method 1—intramyocardial delivery (injection) of stem cells only, without a retaining matrix. (B): Method 2—seeding of cells into a patch-like matrix, which is then implanted onto the epicardium via sutures or glue. (C): Method 3—intramyocardial injection of cells/active ingredient retained in a gel matrix, either during an open surgery (thoracotomy) or in a minimally invasive manner (percutaneously, etc.).

Figure 3

The NOGA^® system allows visualization of the LV contraction in 3D. NOGA is able to map the heart in a full 360° rotation. (A,C): unipolar voltage maps (mV) and (B,D): regional wall motion maps by local linear shortening (LLS%) can help the electromechanical assessment of the myocardium. NOGA shows viability on the left column; dense scarring is visible at the apex and the antero-septal wall (red); scar area (<0.5 mV) = RED; viable tissue (>1.5 mV) = PURPLE. Comparing the bipolar and unipolar maps, NOGA is able to define border zone areas better.