Thermally sensitive and tunable water-soluble polymer molds for the preparation of porous hydrogels

Porous hydrogels are highly sought-after biomaterials for regenerative medicine and 3D cell culture media. For such purposes, direct contact between the hydrogels and organic solvents during the synthesis step must be avoided as much as possible. In this work, porous water-soluble molds, composed of a thermosensitive and melt-processable, i.e. thermoplastic, polyvinyl alcohol (PVA), are used to prepare porous hydrogels. The process offers a high level of control over the porosity features, including full pore interconnectivity and tunable average pore size from nearly 75 μm to 200 μm – the typically targeted range for cell growth in a 3D scaffold. The porous PVA molds are prepared by the sequential process of (1) melt-extrusion of a polystyrene (PS)/PVA co-continuous blend, (2) quiescent annealing to tune the morphology, (3) and selective extraction of the PS phase. The gelling solution is injected in the PVA molds at low temperature – i.e. < 50 °C when the molds are insoluble. Once the solution has gelled, the PVA molds are extracted in hot water – i.e. > 50 °C, over which the molds are fully water soluble, yielding porous hydrogels with nearly comparable macroscopic and microscopic features to the PVA molds, as revealed by electron microscopy and microcomputed tomography. The approach is demonstrated herein with sodium alginate hydrogels, and could be extended to other types of gel chemistries. • Porous hydrogels are prepared from water-soluble polyvinyl alcohol (PVA) porous molds • PVA molds are prepared from melt-processed co-continuous blend of PVA and polystyrene • Thermoplastic PVA is thermally sensitive, from insoluble below 50 °C to soluble above • Hydrogels possess fully continuous porosity with tunable pore size from 75 to 200 μm • Method is compatible with physical and chemical crosslinking strategies