Cardiovascular disease represents a major disease burden. Modern pharmacotherapy, in combination with interventional and surgical approaches, has substantially improved life expectancy for many patients. Yet, current therapies are not able to solve a causal problem, the loss of cardiomyocytes. Regenerative approaches with pluripotent stem cell-derived cardiomyocytes (PSC-CMs) have shown the ability to remuscularize the injured heart in various preclinical models. In this chapter, we summarize tissue engineering approaches and discuss the use of the cryoinjury guinea pig model for preclinical studies.