Tissue Engineering

Overview

Cardiac tissue engineering promises to deliver new methods for repairing damaged myocardium following infarction and regenerating diseased myocardium resulting from maladaptive cardiac hypertrophy. We also envision that creating disease models in vitro will aid in understanding cardiac disease progression and pathophysiology. Further, this approach represents a way to simply and rapidly screen new cardiac pharmaceuticals to speed-up the drug discovery process, accelerating the time-to-market for new therapies.

Multiscale coupling in three dimensions remains a key problem in cardiac tissue engineering. Myocardium is a highly specialized tissue type requiring structure-function relationships to be preserved from ion channels and sarcomeres at the nano/micro scales to tissue and organ level function at the macroscale. Our research is focused in on engineering the cellular microenvironment to control myogenesis from the “bottom-up.” In other words, controlling assembly at the single-cell level combined with organized cell-cell organization and self-assembly through the tissue, organ and whole organism levels.

• Muscular Thin Films
• Vascular Smooth Muscle MTFs

Muscular Thin Films

Primary Investigator: Adam W. Feinberg, Ph.D.

Muscular thin films (MTFs) are a biohybrid material that integrates a tissue engineered monolayer of cardiac muscle cells with a thin, elastic film. This biotic-abiotic composite combines advantages of both materials; mainly excellent contractile strength, spatial control of cell alignment from the micrometer to centimeter length scales and superb handling characteristics that allow the near limitless formation of different shapes. We have demonstrated that MTFs can be used to fabricate a variety of muscle powered actuators and devices. These “soft robotic” applications are an exciting proof-of-concept demonstration of how muscle can be utilized as a material for building many things. Just like muscle is the universal actuator in most large animals, muscle has the same potential to be used to power engineered systems where no synthetic alternative is available. See our Science paper on this topic.

Clinical applications remain the ultimate goal for MTFs where the ability to closely match wild-type (natural) muscle structure and function provides key advantages. First, the MTF can be used as a simple, biomechanical in vitro model for a laminar layer of the ventricular wall. While regenerating an entire heart likely lies many decades off in the future, we can build a single layer of the ventricle right now. Second, we are building MTFs that mimic both healthy and cardiomyopathic myocardium, evaluating the structural and functional differences between the two. Third, we are using these in vitro systems to evaluate drug effects on contractility to determine both toxicity and efficacy of current and future therapeutic compounds.

Vascular Smooth Muscle MTFs

The role of vascular smooth muscle (VSM) is an important area of research for diseases ranging from heart attack and stroke to traumatic brain injury. MTFs can be built using VSM instead of cardiomyocytes, producing a powerful platform for in vitro studies of structure-function relationships in VSM pathophysiology. Current efforts are aimed at better understanding the mechanism behind vasospasm following subarachnoid hemorrhage and traumatic brain injury. This will serve as a test-bed for screening new therapeutic compounds as well as learning how current treatment paradigms affect VSM contractility.