Extracellular matrix is the material that gives tissues like skin, cartilage, or tendon their strength and stretch. It’s been hard to make well in the lab, but scientists report new success.
The key was creating a culture environment that guided cells to make extracellular matrix (ECM) themselves.
In the journal Biomaterials, the team reports culturing cells to make ECM of two types and five different alignments with the strength found in natural tissue and without using any artificial chemicals that could make it incompatible to implant.
Using artificial materials provides strength, but those don’t interact well with the body. Attempts to extract and build upon natural ECM have yielded material that’s too weak to re-implant.
The team at Brown University tried a different approach to making both collagen, which is strong, and elastin, which is stretchy, with different alignments of their fibers. They cultured ECM-making cells in specially designed molds that promoted the cells to make their own natural but precisely guided ECM.
Cells huddled together
As the cell culture grows, cells pull on each other, aligning the extracellular matrix.
“What we hypothesized is that the cells are making it the same way they do in the body, because we’re starting them in a more natural environment,” says lead author Jacquelyn Schell, assistant professor (research) of molecular pharmacology, physiology, and biotechnology. “We’re not adding exogenous materials.”
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The strategy built on the insight that when cells clump together and grow in culture, they pull on each other and communicate as they would in the body, Schell says. The molds therefore were made from agarose so that cells wouldn’t stick to the sides or bottom. Instead they huddled together.
Molds of different shapes
To guide ECM growth in particular alignments, the researchers used molds with very specific shapes, often constrained by pegs the cells had to grow around.
For instance, to make a rod with collagen fibers aligned along its length (like a tendon) they cultured chondrocyte cells in a dog bone-shaped mold with loops on either end. To make a skin-like “trampoline” of elastin, where the ECM fibers run in all directions, they cultured fibroblast cells to grow in an open area suspended at the center of a honeycomb shape.
“The placement of the pegs that this group of cells wraps itself around and then exerts force on each other is what dictates their alignment and the direction of the ECM they are going to synthesize,” says senior author Jeffrey Morgan, professor of medical science and engineering. “That’s a new ability to control the cells’ synthesis of extracellular matrix.”
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After the researchers grew various forms of ECM, they did some stress testing. They took the dog bone-shaped tissues to the lab of Christian Franck, assistant professor of engineering, and together made precise measurements of the tissue strength under the force of being pulled apart. The measurements confirmed the self-assembled tissue was about as strong as that found in some of the body’s tissues, such as skin, cartilage, or blood vessels.
The team’s next goal is to identify a prospective clinical application, Morgan says. The lab will pursue the needed testing to see if this new way of growing ECM can help future patients.
The Department of Defense and the National Science Foundation funded the study.
Source: Brown University
