A team of researchers at the University of Toronto, led by Professor Craig Simmons (BME, MIE), have described a novel method for engineering soft connective tissues with mechanical properties resembling those of native tissues. This finding, published in Advanced Functional Materials, has promising implications in the generation of more realistic tissues and organs for regenerative medicine.
“Soft connective tissues, including heart valves, possess highly nonlinear and anisotropic mechanical properties that haven’t been accurately replicated in tissue-engineered structures before,” says Bahram Mirani, an MIE PhD candidate and the lead author of the paper.
“Current tissue-engineered heart valves often fall short of accurately mimicking the intricate mechanical properties of native valves, leading to their eventual failure.”
The research team’s approach combines computational modelling, statistical optimization and a cutting-edge fabrication method known as Melt Electrowriting (MEW). A fusion of 3D printing and electrospinning, MEW enables the precise deposition of fine fibres with complex architectures. This method stands out for its ability to create structures with microscopic features that mimic native tissue mechanics.
“Melt Electrowriting is a powerful biofabrication method to produce intricate fibre architectures,” says Mirani.
“Its ability to precisely print fibres with complex shapes in specific patterns has garnered significant attention in the biomedical field, especially in recent years.”
A critical feature of soft connective tissues is their nonlinearity — how a tissue stiffens as it is stretched — and anisotropy, which means that the tissue’s stiffness varies depending on the direction it is stretched. The MEW method, coupled with computational modelling, enables the replication of these intricate mechanical characteristics.
“Without an optimization method or computational modelling, we would have had to test hundreds of conditions experimentally,” says Mirani. “Through computational modelling, we reduced the number of experimental conditions needed for optimization down to only five. This significantly accelerated the entire optimization process.”
The research team, which included collaborators from Queen’s University and the University of Ottawa, say the new method has far-reaching implications beyond cardiovascular applications.
“While our examples focused on heart valve and pericardium tissues, the methodology we’ve developed is applicable to a wide range of tissues and organs with non-linear mechanical properties, such as tendons, ligaments and skin,” says Mirani.
The ultimate goal of this research is to develop living tissue constructs that can be implanted into patients, such as children with congenital heart conditions. Implanted engineered tissues could grow and remodel alongside the patient, potentially reducing the need for multiple interventions over their lifetime.
“Current treatments for children born with defective heart valves are quite limited,” says Simmons, the corresponding author of this research.
“The living replacement heart valves engineered with this new biofabrication approach have unmatched mechanical function, which we expect will contribute to longer-term success than what is possible currently.”
