Biomedical Engineering News

The creation of a soft polymer bowl that acts as an artificial womb by mimicing the soft tissue of a mammalian uterus has allowed scientists to observe embryonic development between the fourth and eighth day of typical development. Hitherto, scientists were able to observe the fertilized egg and blastocyst, but had great difficulty viewing embryonic behavior in the stages of development afterwards.

“Using our unique materials and techniques we have been able to give our research colleagues a previously unseen view of the incredible behavior of cells at this vital stage of an embryo’s development,” says University of Nottingham Professor of Tissue Engineering, Kevin Shakesheff. Shakesheff and his team applied their techniques in surveying mouse embryos and recently published their findings in an article for Nature Communications.

Using the same soft polymer culture methods, scientists at Cambridge University tracked the section of cells destined to form the head in a similar mouse model. It was discovered that the “head” cells originated from one or two blastocyst stage cells and that cells from outside the embryo signaled the migration and clustering of these cells (the “head” cells). The rest of the embryonic cells also appear to be led by the same pioneer cells from the blastocyst stage.

Shakesheff believes their findings may have important applications in the future of regenerative medicine and developmental biology: “If we could harness this remarkable ability of the human body to self-form, then we could design new medical treatments that cure diseases that are currently untreatable. For example, diseases and defects of the heart could be reversed…”

Researchers from Leibniz University and Hanover Medical School recently published results in a study observing the biomechanical properties of heart valve scaffolds after different types of preservative treatments. Advancing the strategies used in preserving and handling scaffolds is crucial and may lead to improved implant compatibility and longevity.

When patients require heart valve replacements, there are two common sources: artificial mechanical valves designed from synthetic materials or biological implants made from xenografts (tissue taken from another specie) or a combination of the two. The most common xenograft tissue for heart valves comes from pig hearts because they are anatomically similar to human hearts and after proper laboratory conditioning do not require a lifetime of anticoagulant prescriptions.

According to Professor John Jansen, DDS, PhD, Chairman of the Department of Biomaterials at the Radboud University Nijmegen Medical Center,  “Advances in heart valve technology are essential for the improvement of patient care… The authors have discerned critical methods for heart valve scaffold preservation that may fundamentally change the way that heart valve reconstruction is performed.”

After valves are dissected from porcine hearts, they are decellularized to leave behind a functioning scaffold and freeze-dried for storage and transport. Between the stages of decellularization and freeze-drying, the scaffold is often chemically treated. In the present study, researchers tested the effects of three chemical treatments on porcine valve scaffolds:

1. Without lyoprotectant, a substance used to safeguard the scaffold during its drying stages
2. With a 5% sucrose solution, which forms hydrogen bonds with dried tissue proteins and affects the final tissue porosity
3. With a 2.5% sucrose and a 2.5% hydroxyl ethylene starch (HES), which raises the glass transition temperature, or the temperature at which a material is no longer able to revert to its starting structure

Afterward, the scaffolds  were investigated with respect to several physical parameters, including their elastic modulus and pore size:

Elastic Modulus
The elastic modulus is a measure of the ability of a material or tissue to revert back to its starting state after the application of a force. Decellularization decreases the elastic modulus of the tissue. Additionally, treatment (1) without lyoprotectants resulted in tissue similar to the decellularized state, while the presence of sucrose in treatments (2) and (3) produced tissue with a higher elastic modulus than treatment (1), closer to that of native tissue. Sucrose is known to form hydrogen bonds with freeze-dried tissue proteins and shows promise in preserving the elastic modulus of the scaffolds.

Pore Size
Pore size is a measure of the amount of free space within a porous material or matrix. Freeze-drying without the addition of lyoprotectants (1) created the largest pore sizes, but left a rather disintegrated scaffold. Use of lyoprotectants yield  looser networks of collagen and elastin fibers, as well as larger pore sizes than native tissue. Cells may adhere better to more porous freeze-dried tissues, but additional studies are required to confirm this.

Thus, by investigating the effects of various treatments on scaffolds it was found that sucrose based treatments produced an elastic modulus closer to native tissue, whereas lyoprotectant based treatments yielded an intact scaffold with pore sizes larger than in native tissue. By understanding these parameters and optimizing them, scientists hope to improve scaffold longevity and compatibility, thus improving patient care.