Controlled Positioning of Cells in Biomaterials—Approaches Towards 3D Tissue Printing

Abstract

Current tissue engineering techniques have various drawbacks: they often incorporate uncontrolled and imprecise scaffold geometries, whereas the current conventional cell seeding techniques result mostly in random cell placement rather than uniform cell distribution. For the successful reconstruction of deficient tissue, new material engineering approaches have to be considered to overcome current limitations. An emerging method to produce complex biological products including cells or extracellular matrices in a controlled manner is a process called bioprinting or biofabrication, which effectively uses principles of rapid prototyping combined with cell-loaded biomaterials, typically hydrogels. 3D tissue printing is an approach to manufacture functional tissue layer-by-layer that could be transplanted in vivo after production. This method is especially advantageous for stem cells since a controlled environment can be created to influence cell growth and differentiation. Using printed tissue for biotechnological and pharmacological needs like in vitro drug-testing may lead to a revolution in the pharmaceutical industry since animal models could be partially replaced by biofabricated tissues mimicking human physiology and pathology. This would not only be a major advancement concerning rising ethical issues but would also have a measureable impact on economical aspects in this industry of today, where animal studies are very labor-intensive and therefore costly. In this review, current controlled material and cell positioning techniques are introduced highlighting approaches towards 3D tissue printing.

Bio-ink properties and printability for extrusion printing living cells

“…30 3D bioplotting, first introduced by Landers et al 3,4 is an extrusion based method that can continuously dispense materials (i.e., 'ink') and biological cells from a movable dispensing head or onto a moving stage to form patterns predesigned through computer-aided design (CAD) tools 4 . This method has less 35 geometrical limits than most of the conventional methods and can deposit material and cells within tens of minutes 5 . Ink development can be considered as one of the most challenging aspects in the bioprinting process.…”

Biofabrication: an overview of the approaches used for printing of living cells

“…The printer design is generally simple, consisting of a 3-axis robot that controls the movement of either pneumatically or volumetrically driven displacement pens or syringes with a typical nozzle diameter of 150-300 µm. The utilisation of extrusion approaches for cell printing have recently been reviewed (Chang et al 2011;Fedorovich et al 2007;Wang et al 2010;Wüst et al 2011).…”

“…The work of Klebe and co-workers (Klebe 1988) in 'cytoscribing' laid the foundation for the precise patterning of living cells on surfaces, but it was the more recent advances in AM and CAD/CAM that have seen the advent of several bioprinting technologies that can actually deposit living cells. Several reports outline progress in cell printing to date (Binder et al 2011;Burg and Boland 2003;Calvert 2007;Campbell and Weiss 2007;Derby 2012;Guillemot et al 2010a;Guillotin and Guillemot 2011;Mironov et al 2006;Wüst et al 2011;Xu et al 2011b).…”

A dual crosslinking strategy to tailor rheological properties of gelatin methacryloyl

“…Briefly, GelMA was prepared by reaction of type A gelatin with methacrylic anhydride as in the following: 7.95 g of Na 2 CO 3 and 14.65 g of NaHCO 3 were dissolved in 1 L distilled water to produce 0.25 mol/L carbonate-bicarbonate (CB) buffer solution. Following that, 50 g of gelatin was dissolved into 500 mL of the as-prepared buffer.…”

“…The classic tissue engineering strategy is to seed specific cells isolated from a biopsy onto a three-dimensional (3D) scaffold, occasionally incorporating growth factors, to provide a temporal support for cell proliferation, differentiation and eventually formation of neotissue [2] . One major limitation of this strategy is the lack of precision in cell placement due to manual cell seeding; it is difficult to place different cell types at certain position depending on the type and function of a tissue [3] . To overcome this drawback, an automated and precise technology known as 3D bioprinting has gained scientists' interest in recent years.…”