Consider Fast Stress Relaxation for improved Tissue Engineering

by Amanda Chase, PhD
April 18, 2023

Humans lack the ability to efficiently regenerate tissues and organs. Unfortunately, it is also relatively easy to lose human tissue or organs due to birth defects, disease, or sudden trauma. One new area of scientific work that would have potential in addressing this need is tissue engineering. The use of biomaterial (material that can interact with the body’s system) can create functional tissues to repair, restore, or replace damaged tissue or organs. This area has especially grown in the last few years with growth of the stem cell field, as stem cells can develop into many different types of cells. Additionally, tissue engineering provides an environment to test potential new drugs on disease, an area that could be critical for improving the current treatment development pipeline.

But what is engineered tissue? It is a combination of cells, biomaterials, and a scaffold to form a 3D “tissue”. The scaffold is a structure, artificial or natural, that allows cells to form to mimic real tissues. This allows studies to be carried out in environments more closely resembling what is seen in the body, especially compared to cells grown in 2D on a plate. Therefore, striving to create engineered tissue that is close to natural is critically important.

In a recent publication in Journal of Biomedical Materials Research, first author Mahdis Shayan and senior authors Sarah Heilshorn and Ngan Huang developed a hydrogel scaffold that better allowed endothelial cell behavior to be studied in a more physiological context. Vascular endothelial cells (ECs) line the inside of blood vessels and interact with circulating blood elements. In conditions of heart disease, ECs initiate the formation of blood vessels. This can also be leveraged for the creation of engineered tissues that are vascularized. To improve the creation of these vascularized engineered tissues, it is important to consider that ECs respond to microenvironment cues, including from the extracellular matrix (ECM).

Vascular sprouting in HUVECs. Cells isolated from umbilical cord vein (HUVEC; green) were combined with fibroblast cells (red) in 3D hydrogels (scaffold). Vascular sprouting was only seen with fast stress relaxation (top panels) and slow stress relaxation if low stiffness (bottom left).

In the body, ECMs show stress relaxation, described as a force applied by the cell that results in matrix remodeling and the subsequent relaxation of stress. Here, the research team was able to develop hydrogels (scaffold) that could be independently tuned for different stress relaxation rates to uniquely enable studying EC behavior in a well-controlled environment. They were also able to look at the role of both substrate stiffness and stress relaxation rate in EC responses and found that the two mechanical cues had a different effect on endothelial behavior. Specifically, the fast-relaxing, low-stiffness hydrogel is a suitable choice for supporting vascularized engineered tissues. Further, this work showed a necessary role of stress relaxation rate in controlling endothelial behavior, suggesting that stress relaxation rate is an important consideration for tissue engineering, especially vascularized engineered tissue.

Other authors include Michelle Huang, Renato Navarro, Gladys Chiang, Caroline Hu, Beu Oropeza, Patrik Johansson, Riley Suhar, Abbygail Foster, Bauer LeSavage, Maedeh Zamani, Annika Enejder, and Julien Roth.

Mahdis Shayan, PhD

Ngan Huang, PhD

Sarah Heilshorn, PhD