Methodic Strategy Developed for 3D Tissue Engineering of Viable Organ Implants

Researchers in Singapore have developed a simple way to organize cells and their microenvironments in hydrogel fibers. Their novel technology provides a practical template for constructing complicated structures, such as liver and fat tissues.

The investigators published their findings August 19, 2013, in the journal Nature Communications. According to the Institute of Bioengineering and Nanotechnology (IBN; Singapore) executive director Prof. Jackie Y. Ying, “Our tissue engineering approach gives researchers great control and flexibility over the arrangement of individual cell types, making it possible to engineer prevascularized tissue constructs easily. This innovation brings us a step closer toward developing viable tissue or organ replacements.”

IBN team leader and lead research scientist, Dr. Andrew Wan, elaborated, “Critical to the success of an implant is its ability to rapidly integrate with the patient’s circulatory system. This is essential for the survival of cells within the implant, as it would ensure timely access to oxygen and essential nutrients, as well as the removal of metabolic waste products. Integration would also facilitate signaling between the cells and blood vessels, which is important for tissue development.”

Tissues designed with preformed vascular networks are known to foster rapid vascular integration with the host. Generally, prevascularization has been achieved by seeding or encapsulating endothelial cells, which line the interior surfaces of blood vessels, with other cell types. In many of these approaches, the eventual distribution of vessels within a thick structure is based on in vitro cellular infiltration and self-organization of the cell mixture. These are slow processes, frequently leading to a nonuniform network of vessels within the tissue. As vascular self-assembly requires a large concentration of endothelial cells, this technique also greatly restricts the number of other cells that may be co-cultured.

Alternatively, scientists have attempted to direct the distribution of newly formed vessels via three-dimensional (3D) co-patterning of endothelial cells with other cell types in a hydrogel. This approach allows large concentrations of endothelial cells to be placed in specific areas within the tissue, leaving the rest of the construct available for other cell types. The hydrogel also acts as a reservoir of nutrients for the encapsulated cells. However, co-patterning multiple cell types within a hydrogel is not easy. Traditional techniques, such as micromolding and organ printing, are limited by large volumes of cell suspension, slow cell assembly, complicated multistep processes, and costly instruments. These factors also make it difficult to scale up the production of implantable 3D cell-patterned constructs. Up to now, these strategies have not been able to achieve vascularization and mass transport through dense engineered tissues.

To overcome these hurdles, IBN researchers have used interfacial polyelectrolyte complexation (IPC) fiber assembly, a unique cell patterning technology patented by IBN, to generate cell-laden hydrogel fibers under aqueous conditions at room temperature. In contrast to other technology, IBN’s unique technique allows researchers to incorporate different cell types separately into different fibers, and these cell-laden fibers may then be assembled into more complex constructs with hierarchical tissue structures. Furthermore, IBN researchers are able to customize the microenvironment for each cell type for enhanced functionality by integrating the appropriate factors, e.g., proteins, into the fibers. Using IPC fiber assembly, the researchers have engineered an endothelial vessel network, as well as liver tissue constructs and cell-patterned fat, which have successfully integrated with the host circulatory system in a mouse model and produced vascularized tissues.

The IBN researchers are now working on applying and further developing their technology toward engineering functional tissues and clinical applications.

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