By Samantha Black, Ph.D.

June 17, 2019 -- On June 5, 2019 researchers from the University of Illinois at Chicago published an article in Materials Horizons reporting the results of their research developing a process that enables 3D printing of biological tissues without scaffold using ink made up of only stem cells. Engineered tissues and organs have been grown in labs using various techniques and with varying levels of success for many years. Recently, the scaffolding approach has typically been used to provide the underlying architecture. However, new research shows that scaffolds may not be necessary for the growth of bioengineered organs and tissues.

3D scaffolds are traditionally described as tools made of polymeric biomaterials (biomaterials that can be degraded via chemical and enzymatic oxidation) which allow recapitulation of extracellular environment of cells by providing attachment sites. This allows for cells to grow in 3D shape by providing structural support for cell attachment and tissue development.

In the advanced manufacturing industry, scaffolds have allowed for assisted in the development of remarkable capabilities in tissue engineering, however they can be problematic. They must be biocompatible with the bioengineered tissue of interest. Moreover, scaffolds should degrade and disappear, but decomposition often does not coincide with the maturation of the organ, and sometimes degradation byproducts can be toxic. Scaffolds also can interfere with the development of cell-to-cell connections, which are important for the formation of functional tissues.

A research team led by Eben Alsberg at the University of Illinois, Chicago have developed a 3D printing process that uses only stem cells. "Our cell only printing platform allows for the 3D printing of cells without a classical scaffold support using a temporary hydrogel bead bath in which printing takes place," Alsberg said.

A biodegradable and photocrosslinkable microgel bead matrix serves initially as a fluid, allowing free movement of the printing nozzle for high-resolution cell extrusion, while also presenting solid-like properties to sustain the structure of the printed constructs. The printed human stem cells, which are the only component of the "bioink", couple together via transmembrane adhesion proteins and differentiate down tissue-specific lineages while being cultured in a further photocrosslinked (exposed to UV light) supporting bath to form bone and cartilage tissue with precisely controlled structure.

“The hydrogel bead bath has unique properties which allow for both printing of the cell-only bioink in complex architectures, and subsequent temporary stabilization of these cell-only structures to allow for cell-cell junctions to form,” Alsberg said. “Using chemistry we can then regulate when the beads go away.”

Other methodolgies have recently been developed for scaffold-free 3D printing such as using magnetic levitation with Gadolinium(iii) which induces intercellular interactions without compromising cell viability. Other technologies to create scaffold-free 3D spheroids and microtissues may lead to additional techniques in bioengineered tissues and organs in the future.

The stem-cell based scaffold-free technology has been used to 3D print a cartilage ear and a rodent-sized "femur" in the hydrogel bead bath. The cells they printed were able to form stable, cell-cell connections through specialized proteins. Ultimately, this technology may shift the paradigm of 3D printing strategies and impact the fields of regenerative medicine, drug development, and developmental biology.


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