Building Hearts | Kit Parker | TEDxBoston

Key Concepts

• Disease Biophysics Group: A research team at Harvard School of Engineering and Applied Sciences and Children's Hospital focused on building artificial hearts for children with congenital heart defects.
• Cardiac Myocytes: Heart muscle cells, which are the fundamental building blocks for artificial hearts.
• Extracellular Matrix (ECM): A network of proteins (collagen, elastin, fibronectin) that provides structural integrity and coordinates cell behavior in biological tissues.
• Nanofiber Scaffolds: Artificial structures made of nanofibers that mimic the ECM, providing a framework for cells to grow and organize.
• Fibroagogenesis: The process of forming fibrous structures from proteins.
• Heterotopic Heart Transplant: A procedure where a newly built heart is attached alongside the patient's existing heart.
• Modular Heart Design: Building a heart by creating and assembling individual functional components (valves, vasculature, musculature).
• Focus Rotary Jet Spinning: A manufacturing technology used to create nanofiber scaffolds for tissue engineering.
• Helical Wrapping: The specific architectural arrangement of heart muscle that optimizes pumping efficiency.

Building Hearts for Children: A Biophysics Approach

Kit Parker, from the Disease Biophysics Group at Harvard School of Engineering and Applied Sciences and Children's Hospital, discusses the ambitious goal of building functional hearts for children born with malformed hearts. The group's approach is rooted in understanding the heart as an incredibly complex biological machine and utilizing cells as their primary building material.

The Heart: An Engineering Marvel

Parker begins by highlighting the remarkable nature of the human heart, describing it as a "biochemically powered electrically activated pressure and volume regulated two-state tandem mechanical pump with a mean time to failure of two billion cycles." He emphasizes the regenerative capacity of cardiac myocytes, noting that individuals are born with a fixed number of these cells, which continuously synthesize proteins and rebuild themselves throughout life.

Challenges in Cardiac Science and Engineering

Despite centuries of study, Parker points out significant gaps in our understanding of heart disease. He cites the high failure rates in clinical trials for new therapeutics (90% in Phase 1, 50% in Phase 3) as evidence that current knowledge is incomplete. This has led his team to revisit fundamental aspects of cardiac anatomy, a field that saw a decline with the rise of reductionist approaches like molecular biology. The team's work involves questioning long-held assumptions in textbooks, as some "facts" may be based on early assumptions rather than empirical evidence.

A Modular Approach to Heart Construction

The heart, though perceived as a single organ, is composed of four muscular chambers, valves, vasculature, and innervation. Parker's team adopts a modular approach, aiming to build each component separately before integrating them. Their primary focus is on the approximately 40,000 children born annually in the US with malformed hearts who require surgical intervention, potentially including heterotopic heart transplants.

Engineering Extracellular Matrix Scaffolds

A common architectural theme in biological tissues is the reliance on nanofiber scaffolds, such as collagen and elastin, which form the extracellular matrix (ECM). This ECM provides structural integrity and coordinates cellular activity. The group's strategy involves developing manufacturing technologies to create these fiber scaffolds and then leveraging the self-organizational and self-assembly properties of cells to build functional tissues and organs.

Developing Functional Heart Valves

The initial plan was to focus on building musculature, but a personal experience with his daughter's heart murmur shifted the priority to heart valves. Parker explains the challenges with current pediatric heart valves: children outgrow them, necessitating repeated open-heart surgeries. Furthermore, rheumatic fever and strep infections, particularly prevalent in Africa, cause significant heart valve disease, as the immune system can attack these structures.

Inspired by an idea for burn dressings using ECM proteins, Parker adapted a "cotton candy machine" to spin ECM proteins into fibrous structures. This technology, termed fibroagogenesis, allows for the rapid fabrication of heart valves. Unlike traditional valves that take weeks to produce, these can be made in about 10 minutes. The valves are constructed from composite nanofibers of natural and synthetic polymers, making them stretchy and collapsible. This allows for minimally invasive implantation through the femoral artery, avoiding sternotomy and reducing scarring. The valves undergo rigorous mechanical testing (over two billion cycles) and animal studies to ensure functionality. A key innovation is the use of natural polymers, enabling the valve to grow with the patient as their own cells integrate and rebuild the structure.

Engineering Vasculature for Blood Flow

The heart is a metabolically demanding organ, consuming a significant portion of oxygen and nutrients. It possesses its own intramural vasculature to sustain itself. Applying similar principles, the team uses a focus rotary jet spinning technique, essentially a sideways cotton candy machine with a hair dryer, to spin fibers onto a mandrel to create blood vessel scaffolds. These acellular grafts are implanted, and blood flow encourages endothelialization, where the body's own cells line and reconstruct the vessel walls. The technology can create complex branched vascular structures. Early animal tests have shown successful maintenance of a patent lumen for months. The modular approach allows for separate testing of each component, including vascular grafts, before integration into a complete heart.

Constructing the Muscular Pump: The Challenge of Helical Architecture

The heart's musculature is described as a two-dimensional tissue wrapped into a three-dimensional form, with muscular layers wrapped around chambers. This laminar architecture is crucial for organs controlling volume or flow rates. While 3D printing is often discussed for organ construction, Parker argues it faces scaling challenges, from the nanometer scale of cellular cues to the centimeter scale of the heart.

His team's focus is on focus rotary jet spinning to create nanofiber scaffolds seeded with cardiac cells. These cells form a syncytium (a multinucleated mass of cytoplasm) that can beat. They have successfully built small, beating ventricular-like structures, but these are only a few cell layers thick and lack the musculature for significant pumping.

The critical realization is that the heart is not wrapped circumferentially like a toilet paper roll but helically. This helical wrapping, squeezing from the bottom up, optimizes ejection fraction. Traditional 3D printing struggles to create these angled fiber scaffolds. By orienting the mandrel sideways and spinning fibers at an angle, the team can build these helical structures, achieving greater stroke volume. They utilize a sugar mandrel, which is dissolved after fiber wrapping, allowing for cell seeding. The team is progressing towards building four-chamber hearts, with scaffolds that are stiffer for handling but typically soft.

Future Outlook and Applications

The ultimate goal is to make modular components of the heart available to patients in the near future. Vascular grafts, tri-leaflet valves, and patches for myocardial repair could be applicable to adults. However, the primary focus remains on addressing the needs of the 40,000 children born annually with malformed hearts.