3D-printing method enables fabrication of collagen tissue oriented in multiple directions (2025)

Collagen, a prevalent and predominant part of the structure of bodies, still has some mystique surrounding the finer aspects of its existence. In a new study, researchers look into the mechanism of orientation within collagen to elucidate some of the lesser-known aspects of this protein and how it can be used in future applications.

The body is full of complexity, even when it comes down to the most minute details, such as the orientation of collagen structures within tissues. Collagen helps to give structure, stability and mechanical strength to our tissues. Although a few methods already exist that can model collagen structures, none are as precise as needed, nor do they keep cost-effectiveness or safety in mind.

Researchers from Yokohama National University have developed a method to fabricate complex-oriented tissues with multiple directionality using fluidic devices and three-dimensional (3D) printing. Their study is published in ACS Biomaterials Science & Engineering.

"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," said Kazutoshi Iijima, associate professor at Yokohama National University and author of this study.

Current methods, including magnetic alignment and electrospinning, have challenges: magnetic beads that remain in the model for the former and the use of a volatile organic solvent for the latter. In the new model, there is no need for magnetic beads or volatile chemicals, only collagen. However, the challenge of mimicking complex oriented structures, as found in the skin dermis or skull bone, remained.

Researchers found that using a technique that utilizes flow to orient these collagen fibers and cells can be fabricated using a 3D printer. The orientation of the collagen bundles affects the behavior and function of the cell, so having the correct orientation for the tissue is key to its proper function.

The researchers used a type 1 collagen solution mixed with cells in a fluidic channel (a passageway or channel designed to steer the flow of fluids, usually on a micro-scale), using a master mold that has been 3D-printed. Using these conditions, researchers developed a model that is capable of achieving a fine, micro-oriented structure in both horizontal and vertical directions for multi-directionally oriented tissues.

This was achieved by intentionally guiding the flow along the collagen structures to orient the fibers, fibrils and fibroblasts as desired. The control over the size and direction of the oriented collagen hydrogels offers accurate fine tissue fabrication, a detail this type of fabrication technology has always lacked.

"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, author of the study and professor at Yokohama National University.

Further development of the tissue models will illuminate the importance of functionality that orientation brings. Researchers hope to be able to apply this method for transplantation and in vitro tissue models in the future.

More information:Mizuki Iijima et al, Fabrication of Multiscale, Multidirectional Orientated Collagen Hydrogels with Guided Cell Alignment Using Fluidics and a Three-Dimensional Printing, ACS Biomaterials Science & Engineering (2025). DOI: 10.1021/acsbiomaterials.4c02156