We present millimeter to centimeter-sized injectable neural scaffolds based on macroporous cryogels. The polymer-scaffolds are made from alginate and carboxymethyl-cellulose by a novel simple one-pot cryosynthesis. They allow for surgical sterility by means of autoclaving, and present native laminin as an attachment motive for neural adhesion and neurite
This work combines the power of 3D additive manufacturing with clinically advantageous minimally invasive delivery. We obtain porous, highly compressible and mechanically rugged structures by optimizing a cryogenic 3D printing process. Only a basic commercial 3D printer and elementary control over reaction rate and freezing are required. The porous hydrogels obtained are capable of withstanding delivery through capillaries up to 50 times smaller than their largest linear dimension, an as yet unprecedented compression ratio. Cells seeded onto the hydrogels are protected during compression. The hydrogel structures further exhibit excellent biocompatibility 3 months after subcutaneous injection into mice. We finally demonstrate that local modulation of pore size grants control over vascularization density in vivo. This provides proof-of-principle that meaningful biological information can be encoded during the 3D printing process, deploying its effect after minimally invasive implantation.
Cryogels are macroporous materials that display remarkable properties, such as high pore interconnection, large surface to volume ratio, and high mechanical stability, making them good candidates for 3D cell culture. However, shaping cryogels remains challenging because of the harsh conditions of synthesis at temperatures as low as −80 °C. In this paper, a solution for the 3D printing of functionalized cryogels is proposed. A microfabricated dispensing probe allowing the last second mixing of cryogel precursors as well as control of the temperature of the extruded material during printing is presented. This dispensing tool allows multilayer 3D printing of cryogels with on demand local pore size change through the control in temperature of the dispensed solution. Moreover, thanks to advanced functionalization of the scaffold, cells can be cultured in 3D within the printed scaffold and exhibited spreading. The ability to tune the pore size of the printed cryogels allows to select during printing where cells will get seeded.
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