The Ogle Lab is pushing the boundaries of 3D bioprinting for cardiac tissue engineering to create complex model systems that extend well beyond the “wood piles” and simple geometric shapes prevalent in the literature. This work is enabled by basic studies to understand the interplay between the extracellular matrix, pluripotent stem cells and associated cardiac progeny.
Outcomes of these studies pointed us to unique bioink formulations that can be coupled with multiphoton-based 3D printing to create patch-like structure with features on the scale of a single micron. Patches of this type support cardiac cell organization, can be easily adhered to the failing heart, and have been used successfully in rodent models of cardiac failure to restore function. Large animal studies are ongoing.
In other work, novel, extracellular matrix-based bioinks have also been used to fabricate living, complex, chambered heart structures based on a digital template of the human heart taken via MRI and scaled to the size of a mouse heart (graphic). The chambered structure was printed using the bioink with human induced pluripotent stem cells. The stem cells undergo expansion and differentiation to cardiac muscle after printing to yield structures containing exclusively cardiac cell types and capable of synchronous beating, which can be accelerated with electrical pacing.
To date, we have measured clinically-important, physiologically complex mechanical parameters including pressure dynamics not possible with cardiac microtissues (microscale strips of cardiac muscle and current state of the art) and associated electrical parameters including action potential, calcium transients, and conduction velocity. The utility of this work for the field of cardiology is access to a human model system that can sustain flow profiles and exhibit pressure-volume dynamics characteristic of the native heart.
This model will therefore be useful for understanding remodeling associated with cardiac disease progression imposed by mechanical insult, genetic predisposition, or diet. It will also be useful for testing drug toxicity or efficacy and, given the scale, is amenable to the testing of medical devices and implantation to the heterotopic position in mice and perhaps one day for human transplantation.