PMC:4996398 / 39534-43335 JSONTXT

{"project":"2_test","denotations":[{"id":"27600217-25093879-69475961","span":{"begin":406,"end":409},"obj":"25093879"},{"id":"27600217-23719889-69475962","span":{"begin":647,"end":650},"obj":"23719889"},{"id":"27600217-23260439-69475963","span":{"begin":758,"end":761},"obj":"23260439"},{"id":"27600217-20353253-69475964","span":{"begin":1489,"end":1492},"obj":"20353253"},{"id":"27600217-25047630-69475965","span":{"begin":1602,"end":1605},"obj":"25047630"},{"id":"27600217-25383549-69475966","span":{"begin":1606,"end":1609},"obj":"25383549"},{"id":"27600217-20353253-69475967","span":{"begin":1795,"end":1798},"obj":"20353253"},{"id":"27600217-25047630-69475968","span":{"begin":2192,"end":2195},"obj":"25047630"},{"id":"27600217-25383549-69475969","span":{"begin":2196,"end":2199},"obj":"25383549"},{"id":"27600217-24722236-69475970","span":{"begin":2483,"end":2486},"obj":"24722236"},{"id":"27600217-22336294-69475971","span":{"begin":2998,"end":3001},"obj":"22336294"},{"id":"27600217-24998183-69475972","span":{"begin":3201,"end":3204},"obj":"24998183"},{"id":"27600217-25005170-69475973","span":{"begin":3642,"end":3645},"obj":"25005170"}],"text":"3.4. Alginate as a Bioink and 3D Bioprinting\n3D printing as a technology is available in industrial and home-use applications. The ability to construct customized three dimensional structures on demand using relatively simple materials is leading to a boon in manufacturing sectors. The application of 3D printing technology in the fields of tissue engineering and regenerative medicine has already begun [111]. Bioprinting uses biocompatible materials and cells to form a variety of 3D formats where cell function and viability are preserved within the printed construct. Various 3D bioprinting technologies can already form vascular-like tubes [112], artificial skin [113], cartilage [114], and a wide range of tissue constructs also including stem cells [115]. A public workshop was hosted by the U.S. Food and Drug Administration (U.S. FDA) in October of 2014 under the title “Additive manufacturing of medical devices: An interactive discussion on the technical considerations of 3D printing”. The workshop agenda, participants and presentations held at this workshop are available at the U.S. FDA web sites [116].\n3D bioprinting techniques such as ink-jet and extrusion have the need for biocompatible “inks”. Alginate has shown particular relevance as a bioink due to its compatibility with cells, ease in forming cross-linked hydrogels, and the ability to control biodegradation. Khalil and Sun demonstrate bioprinting of 3D tissue constructs using alginate and endothelial cells [117] and alginate stabilized with gelatin was a suitable matrix for 3D bioprinting of bone-related SaOS-2 cells [118,119]. Common to these reports is a high (\u003e80%) cell viability following bioprinting. These reports also show two different approaches in the design of alginate as a bioink. Khalil and Sun [117] use a multinozzle system that prints alginate + cells and overlays with calcium chloride in order to induce gelation. The addition of a low-melting gelatin together with an alginate solution forms a gel when the solution printed at 37 °C cools. Moreover, addition of a calcium poly phosphate salt or bioglass to the cell‑containing hydrogel led to enhanced biomineralization by SaOS-2 cells [118,119].\nUsing 3D printing technology and alginate as a bioink, Zhao et al. show the advantage of printing Hela cells to form an in vitro cervical tumor model in order to study disease pathogenesis and enable new anti-cancer drug discovery with a more relevant physiological disease model [120]. This report used gelatin together with alginate to initiate gelation prior to printing. The printed construct was further strengthened after printing by subsequent addition of a calcium salt solution. The authors included fibrinogen in the gelatin/alginate formulation to mimic ECM components. Printed HeLa cells formed spheroids which were shown to be more resistant to paclitaxel treatment than HeLa cells grown as a 2D cell culture.\nBy oxidizing alginate, a known technique to “build in” biodegradability [121], Jia et al. demonstrate the interaction of alginate viscosity and density on printability while biodegradability of printed scaffolds containing human adipose-derived stem cells was also described [122].\nOptimization of alginate for use in different printing technologies is, however, necessary. For inc-jet types of printing, droplet formation is impacted by alginate molecular weight, solution viscosity, monomer composition (if ionic cross-linking is to be used to form a gel), and purity which impacts on biocompatibility. Xu et al. studied the characteristics of the droplet formation process using alginate viscosity and shear rate [123]. Furthermore, Gasperini et al. present a bioprinting techniques based on electrohydrodynamic processes to jet droplets of alginate containing cells [124]."}