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Collagen-based method overcomes previous problems to advance tissue engineering and bioprinting

A team of biomedical researchers led by Michael Mak, Ph.D., in the Renaissance School of Medicine at Stony Brook University, has developed a new method of bioprinting physiological materials. Called TRACE (Tunable Rapid Assembly of Collagenous Elements), the method solves previous problems of bioprinting natural materials of the body.

It is also a highly versatile biofabrication technique that will help advance drug development and disease modeling, and potentially impact regenerative medicine. Details of the method are explained in a paper in Nature Materials.

Bioprinting positions biochemicals, biological materials, and living cells for the generation of bioengineered structures. The process uses biological inks (bioinks) and biomaterials, along with computer-controlled 3D printing techniques, to construct living tissue models used in medical research. While 3D printing technologies are newer to medicine and biomedical research, their applications are prominent in industries such as automotive manufacturing.

Researchers point out that despite the potential of bioprinting, achieving functionality in bioprinted tissues and organs has been challenging because biological cells in traditional bioprinted tissues are unable to perform their natural activities in the body—thus rendering most bioprinted tissues unusable for clinical purposes and advanced medical applications.

Mak and colleagues hope TRACE will help rectify this problem in future medical research.

"Our method is essentially a novel platform technology that can be used to print wide-ranging tissue and organ types," says Mak, Associate Professor in the Department of Pharmacological Sciences. "With TRACE, we figured out how to fabricate and manufacture complex user-designable tissue and organ structures via 3D patterning and printing using the body's natural building blocks, particularly collagen, as bioinks in a highly biocompatible manner and with direct incorporation of living cells," he explains.

Collagen (especially Collagen Type I) is the most prominent and abundant protein in the human body. It is a key building block in tissues including skin, muscle, bone, tendon, and vital organs such as the heart. Collagen acts as the "glue" to many tissues and organs and is crucial as the body's natural scaffolding material for holding cells and tissues in place. It also helps direct cells to perform their functions.

According to Mak, because of each of these attributes of collagen in physiological processes, it is a top candidate to be used as a bioink material.

In the paper, titled "Instant assembly of collagen for tissue engineering and bioprinting," the authors explain how with TRACE they can bioprint physiological materials by rapidly accelerating the gelation process of collagen. Their method is mediated by macromolecular crowding, a process in which an inert crowding material is used to speed up the assembly reaction of collagen molecules.

By doing this, they can create tissues composed of the same basic elements as those found inside the body. Then they apply TRACE to generate functional tissues and "mini organs" such as heart chambers.

"TRACE offers a versatile biofabrication platform, enabling direct 3D printing of physiological materials and living tissues, achieving both structural complexity and biofunctionality. This work broadens the scope of controllable multiscale biofabrication for tissues across various organ systems, using collagen as a key component," the authors summarize.