Collagen, one of the most abundant proteins in the human body, plays a critical role in providing structure, stability, and mechanical strength to tissues. Yet, despite its prevalence, some aspects of collagen’s behavior—particularly its orientation within tissues—remain shrouded in mystery. A new study from researchers at Yokohama National University sheds light on this complex topic and introduces a promising new method for fabricating collagen-based tissues with unprecedented precision.

Understanding the orientation of collagen fibers is vital, as it influences cell behavior and tissue function. Existing methods for modeling collagen structures—such as magnetic alignment and electrospinning—have notable drawbacks. Magnetic beads can remain embedded in the final structure, while volatile organic solvents pose safety and environmental concerns. Additionally, these techniques often fall short when it comes to accurately replicating the complex, multi-directional orientations found in natural tissues like the dermis or skull.

In this groundbreaking study, published in ACS Biomaterials Science & Engineering, researchers developed a new method using fluidic devices and 3D printing to guide collagen orientation without relying on harmful chemicals or extraneous materials. “By using a technique that uses flow to orient collagen fibers and cells, it is possible to fabricate complex oriented tissues with multiple directions in flow channels constructed using a 3D printer,” explained Kazutoshi Iijima, associate professor at Yokohama National University and co-author of the study.

The team utilized a Type I collagen solution mixed with cells, injected into fluidic channels formed using a 3D-printed master mold. By precisely guiding the flow of the solution, they were able to align collagen fibers, fibrils, and fibroblasts in both horizontal and vertical orientations—creating fine, micro-structured tissue models that closely mimic the complexity of natural tissue.

This level of control over collagen alignment is a major advancement in tissue engineering. “This system will lead to the customization of tissue-specific models using fine, multidirectionally oriented biomaterial scaffolds for the preparation of various oriented biological tissues,” said Shoji Maruo, co-author and professor at Yokohama National University.

Looking forward, the researchers aim to refine this method further and explore its use in transplantation and in vitro tissue modeling. By replicating the intricate architecture of real tissues, this innovation could open new doors in regenerative medicine, offering safer, more precise, and cost-effective alternatives for building functional biological systems.

By Impact Lab