Scientists believe that a new versatile biofabrication technique will help advance drug development and disease modeling, and potentially impact regenerative medicine.
Researchers from the Renaissance School of Medicine at Stony Brook University say they have developed a new method of bioprinting physiological materials. Called TRACE (Tunable Rapid Assembly of Collagenous Elements), the technique addresses long-standing challenges in bioprinting natural body materials. According to the scientists, it also serves as a versatile biofabrication method that could advance drug development, improve disease modeling, and potentially transform regenerative medicine.
The team published its study “Instant assembly of collagen for tissue engineering and bioprinting” in Nature Materials.
Collagen Fabrication Method
“Engineering functional cellular tissue components holds great promise in regenerative medicine. Collagen I, a key scaffolding material in bodily tissues, presents challenges in controlling its assembly kinetics in a biocompatible manner in vitro, restricting its use as a primary scaffold or adhesive in cellular biofabrication,” write the investigators.
“Here we report a collagen fabrication method termed as tunable rapid assembly of collagenous elements that leverages macromolecular crowding to achieve the instant assembly of unmodified collagen. By applying an inert crowder to accelerate the liquid–gel transition of collagen, our method enables the high-throughput creation of physiological collagen constructs across length scales—from micro to macro—and facilitates cell self-assembly and morphogenesis through the generation of tunable multiscale architectural cues.
“With high biocompatibility and rapid gelation kinetics, the tunable rapid assembly of collagenous elements method also offers a versatile bioprinting approach for collagen over a wide concentration range, enabling the direct printing of cellular tissues using pH-neutral, bioactive collagen bioinks and achieving both structural complexity and biofunctionality.
“This work broadens the scope of controllable multiscale biofabrication for tissues across various organ systems using unmodified collagen.”
Generates Bioengineered Structures
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.
TRACE could help rectify this problem in future medical research, points out Michael Mak, PhD, associate professor in the department of pharmacological sciences research and a co-author of the paper.
“Our method is essentially a novel platform technology that can be used to print wide-ranging tissue and organ types,” explains Mak. “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.
The authors explain in their paper 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.
