Three-dimensional plotting of a cell-laden alginate/methylcellulose blend: towards biofabrication of tissue engineering constructs with clinically relevant dimensions

Abstract

Biofabrication of tissue engineering constructs with tailored architecture and organized cell placement using rapid prototyping technologies is a major research focus in the field of regenerative therapies. This study describes a novel alginate-based material suitable for both cell embedding and fabrication of three-dimensional (3D) structures with predefined geometry by 3D plotting. The favourable printing properties of the material were achieved by using a simple strategy: addition of methylcellulose (MC) to a 3% alginate solution resulted in a strongly enhanced viscosity, which enabled accurate and easy deposition without high technical efforts. After scaffold plotting, the alginate chains were crosslinked with Ca ; MC did not contribute to the gelation and was released from the scaffolds during the following cultivation. The resulting constructs are characterized by high elasticity and stability, as well as an enhanced microporosity caused by the transient presence of MC. The suitability of the alginate/MC blend for cell embedding was evaluated by direct incorporation of mesenchymal stem cells during scaffold fabrication. The embedded cells showed high viability after 3 weeks of cultivation, which was similar to those of cells within pure alginate scaffolds which served as control. Maintenance of the differentiation potential of embedded cells, as an important requirement for the generation of functional tissue engineering constructs, was proven for adipogenic differentiation as a model for soft tissue formation. In conclusion, the temporary integration of MC into a low-concentrated alginate solution allowed the generation of scaffolds with dimensions in the range of centimetres without loss of the positive properties of low-concentrated alginate hydrogels with regard to cell embedding. Copyright © 2015 John Wiley & Sons, Ltd.

Tailoring Hydrogel Viscoelasticity with Physical and Chemical Crosslinking

“…MC was included to dilute the mix during processing, with MC reported to diffuse out after crosslinking and subsequent immersion in medium [33]. The use of MC did not achieve this outcome, in contrast to the very effective N+M, with low ion concentrations maintaining GG in a loosely crosslinked state that remained pipettable due to the pseudoplasticity of the material [23].…”

Biofabrication of 3D Alginate-Based Hydrogel for Cancer Research: Comparison of Cell Spreading, Viability, and Adhesion Characteristics of Colorectal HCT116 Tumor Cells

“…Therefore, in vitro 3D tumor models with human cancer cells have attracted scientists to precisely imitate the features of human cancer tissues (4)(5)(6). Cells modify their metabolism and functionality in 2D cell culture systems since contacts with other cells and with their microenvironments cannot be formed (7,8). To mimic the structural architecture and cellular functions of the extracellular matrix (ECM) in 3D model systems some major characteristics have to be considered: suitable mechanical characteristics and chemical composition, facilitation of cell growth and maintenance, and fostering the transport of nutrients, gas, and metabolic waste, as well as signal transduction (7,9,10).…”

“…They found cell viabilities of 80% 5 h after the process using bone marrow stroma cells. Furthermore, in another study they evaluated around 80% viability of human mesenchymal stem cells one day after the preparation(8).As the compatibility of the construct fabrication with HCT116 cells had been proven, the time dependent behavior of the immobilized HCT116 cells in the 3D hydrogel matrices was investigated up to an incubation period of 8 days (Figure 1C and D). The images show that with an ongoing incubation time the cells start to proliferate throughout the hydrogel matrix and finally are growing out of the hydrogel constructs on the regular well plates.…”

A simultaneous 3D printing process for the fabrication of bioceramic and cell-laden hydrogel core/shell scaffolds with potential application in bone tissue regeneration

“…Cell printing using a 3D printing system provides controllable 3D tissue architecture with homogeneous cell distribution, without the need of cell seeding. Cell printing has been used widely in soft tissue engineering and is now being considered for its potential application in bone tissue regeneration [7][8][9][10][11][12][13][14][15][16][17] .…”