Strategies for tissue engineering cardiac constructs to affect functional repair following myocardial infarction

Abstract

Tissue-engineered cardiac constructs are a high potential therapy for treating myocardial infarction. These therapies have the ability to regenerate or recreate functional myocardium following the infarction, restoring some of the lost function of the heart and thereby preventing congestive heart failure. Three key factors to consider when developing engineered myocardial tissue include the cell source, the choice of scaffold, and the use of biomimetic culture conditions. This review details the various biomaterials and scaffold types that have been used to generate engineered myocardial tissues as well as a number of different methods used for the fabrication and culture of these constructs. Specific bioreactor design considerations for creating myocardial tissue equivalents in vitro, such as oxygen and nutrient delivery as well as physical stimulation, are also discussed. Lastly, a brief overview of some of the in vivo studies that have been conducted to date and their assessment of the functional benefit in repairing the injured heart with engineered myocardial tissue is provided.

Figure 1

Overview of cardiac tissue engineered construct process. (Left Panel) Natural polymers, such as collagen or fibrin, as well as synthetic polymers, such as PLGA, or PNIPPAm, have been used as the biomaterial for the cardiac constructs. (Middle Panel) Preformed scaffolds, such as sponges or decellularized organs, have been used in in vitro systems. Hydrogels have been used in vitro, in situ, where the hydrogel is injected as a liquid directly into the heart wall, or in vivo. Cell sheets can be created in vitro. (Right Panel) When culturing constructs in vitro, oxygen/nutrient delivery of the type of bioreactor used should be taken into consideration. Furthermore, physical stimulation, such as mechanical and/or electrical stimulation can be used to condition the constructs.