By Julian Namerow, Class of 2026
Collagen I is a vital protein found in the extracellular matrix—the structural scaffold between cells—where it provides physical support to tissues. Collagen provides structure at micro and macro scales, and plays a key role in governing biophysical cues that regulate cell behavior. Recently, self-assembled collagen hydrogels have been widely used as tissue models; they have very limited versatility in their creation and can easily break. It has proven to be difficult to precisely control, especially in terms of spatial precision in a living system. A hydrogel also takes a long time to stiffen and hold form, which prevents rapid assembly or accurate positioning of the liquid collagen mix.
Presented in this research are methods for fabricating a form of unmodified collagen type 1, using accelerated collagen assembly kinetics via macromolecular crowding. This means that the collagen mixture is formed within a glycol liquid that induces instant assembly of collagen upon contact. The glycol liquid forces crowding of the collagen molecules, as it is a highly crowded environment, especially at the collagen-glycol interface, where solidification is immediately induced and spread to the middle of the gel.
At a microscopic scale, the collagen can be sprayed onto the glycol solution, instantly forming microgels upon contact, and the microgel easily reaches the scale of cells. Microbundles can be made from the gel being poured into the glycol solution. The micro bundles can be mixed with vascular endothelial cells, and together they condense and initiate tissue formation. They also allow for continuous cell infiltration through the bundles. This is important for transplanting the bundles in vivo. Vascular endothelial cells are needed to support healthy muscle cell development and contractile function, which is relevant for post-printing bioactivities that would occur in the body. Next, researchers demonstrated the rapid assembly of macroscopic collagenous tissue using a multichannel device composed of parallel cylinders. The cylinders were pre-filled with glycol solution, so strip-like collagen gels were formed within seconds. The cellular strips with vascular endothelial cells can subsequently be manufactured into tissue-building blocks.
This method can also be used to create macroscopic strip-like pluripotent tissues with human-induced pluripotent stem cells, with the potential to differentiate into a wide variety of human tissue types. Cell contractility was active in all printed tissues. Furthermore, the research envisions that the bioactive collagenous elements can incorporate various cell types to serve as modular units that can be used to construct larger-scale, vascularized organ systems.
Work’s Cited:
Gong, X., Wen, Z., Liang, Z., Xiao, H., Lee, S., Rossello-Martinez, A., Xing, Q., Wright, T., Nguyen, R. Y., & Mak, M. (2025). Instant assembly of collagen for tissue engineering and bioprinting. Nature Materials, 24(8), 1307–1318.
