Fabrication of Complex Hydrogel Structures Using Suspended Layer Additive Manufacturing (SLAM)

Abstract

There have been a number of recently reported approaches for the manufacture of complex 3D printed cell-containing hydrogels. Given the fragility of the parts during manufacturing, the most successful approaches use a supportive particulate gel bed and have enabled the production of complex gel structures previously unattainable using other 3D printing methods. The supporting gel bed provides protection to the fragile printed part during the printing process, preventing the structure from collapsing under its own weight prior to crosslinking. Despite the apparent similarity of the particulate beds, the way the particles are manufactured strongly influences how they interact with one another and the part during fabrication, with implications to the quality of the final product. Recently, the process of suspended layer additive manufacture (SLAM) is demonstrated to create a structure that recapitulated the osteochondral region by printing into an agarose particulate gel. The manufacturing process for this gel (the application of shear during gelation) produced a self-healing gel with rapid recovery of its elastic properties following disruption. Here, the physical characteristics of the supporting fluid-gel matrix used in SLAM are explored, and compared to other particulate gel supporting beds, highlighting its potential for producing complex hydrogel-based parts.

The rheology of direct and suspended extrusion bioprinting

“… 125 This concentration effect reflects findings of Senior et al , whereby using dyes of differing molecular weights, diffusion into a suspension media was reduced as the molecular weight was increased. 122 At low nanoclay concentrations (0.5%, = 0.001 5 Pa), Jin et al observed that the filament had a very rough surface, likely due to low interfacial tension between the ink and suspension media. With increasing nanoclay concentrations, the storage modulus of the SM was increased and the filament was more regularly circular in the cross section although extrudate swell was reported.…”

“… 121–123 The hairy or dendritic morphology, shown in Table II , gives both short- and long-range interactions between particles and has been shown to give comparable or faster recovery of viscosity than jammed slurries formed by chopping crosslinked gels. 122 Gellan gum has also been used as suspension media by Compaan and colleagues. 124 Gellan gum is weakly thermo-gelling and strongly ionically crosslinked, and so a combination of cross-linking methods can be used to form fluid gels.…”

Emulating Human Tissues and Organs: A Bioprinting Perspective Toward Personalized Medicine

“… 119 , 338 , 452 Additionally, the development of SLAM and FRESH systems facilitate the extrusion of low-viscosity materials that would otherwise be very difficult to print. This has already been explored in the fabrication of soft tissue constructs, 70 , 71 , 75 but other related fields like neurovascular engineering are expected to greatly benefit from suspended manufacturing methods. 51 , 453 The number of cell-based studies involving SLAM and FRESH are few in number, but these are expected to increase in the future with more attempts to build large, complex, multimaterial, and multicellular constructs being reported.…”

“…This process is commonly referred to as suspended layer additive manufacture (SLAM) or freeform reversible embedding of suspended hydrogels (FRESH) depending upon the nature of the fluid gel used for printing. 70 , 71 , 75 In both formats, it is theorized that the fluid gel restricts flow without interacting and mixing with deposited solutions, thus allowing for layering of different materials of varying densities into high resolution constructs. Cross-linkers can then be introduced to promote the gelation of a suspended structure allowing for generation of heterogeneous structures capable of mimicking biological interfaces.…”

Granular hydrogels for 3D bioprinting applications

“…37 To grow complex tissues, some efforts have been focused on the use of biocompatible natural polymers based granular hydrogels. 31,[38][39][40] Those materials usually are formed in bulk, and they are blended into a slurry that behaves like a Bingham plastic. Feinberg and his co-workers reported one of the earliest examples of development of freeform reversible embedding of suspended hydrogels (FRESH) within gelatin: these researches demonstrated the 3D bioprinting of biological hydrogels composed of polysaccharides and proteins that are challenging or impossible to build using traditional fabrication methods.…”