Muscle cells self-organize into spirals, advancing efforts to engineer tiny blood vessels that regulate flow

This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Different tissues need different amounts of blood depending on what they are doing. Meeting those changing demands requires the circulatory system to continually balance how much blood flows to different regions of the body.

That balancing act takes place largely in resistance vessels, microscale arteries that can constrict or dilate to regulate local blood flow. By changing their diameter, these microvessels alter resistance and help control how much blood reaches different tissues at any given time. Despite their critical role, researchers have struggled to recreate resistance vessels with the structure and function of their natural counterparts.

Scientists have produced microscale channels that can carry cell-supporting fluids and have demonstrated techniques to form larger vascular grafts with contractile components. However, engineering microvessels with the cellular architecture needed to allow them to actively change their diameter has remained a significant tissue-engineering challenge. Now, researchers at Vanderbilt University have taken an important step toward building resistance vessels with that capability.

In a study published in Advanced Healthcare Materials, Leon Bellan, associate professor of mechanical engineering and biomedical engineering, and his team found that human smooth muscle cells can spontaneously organize into the helical arrangement found in natural resistance vessels. This alignment is an important architectural feature of the natural vessel wall because it allows contraction of the smooth muscle cells to be coupled to changes in vessel diameter; randomly aligned or longitudinally aligned smooth muscle cells would not have the same effect. The researchers didn't have to pattern microscopic features or physically force the cells into place.

They gave the cells the right biochemical environment, and over time the cells organized themselves in the correct orientation. Additionally, when exposed to endothelin-1 (a molecule that causes smooth muscle cells to contract), the aligned cells exhibited a strong calcium response characteristic of contractile smooth muscle cells. Led by Victoria Vest, a graduate student in the Bellan Lab, the team found that the composition of the proteins on which the cells were growing strongly influenced their organization.

The researchers fabricated microscale channels within slabs of gelatin to mimic the geometry of a resistance vessel and cultured smooth muscle cells on the channel walls to form a medial layer (the portion of a resistance vessel wall responsible for generating forces that can change vessel diameter). Channels coated with collagen IV and fibronectin, or with collagen IV and fibronectin and vitronectin, caused cells to develop helical alignment. Culturing the smooth muscle cells on channel walls coated with collagen IV alone or directly on the gelatin resulted predominantly in longitudinal alignment.