Hydrogel injection molding to generate complex cell encapsulation geometries

Abstract

Biofabrication methods capable of generating complex, three-dimensional, cell-laden hydrogel geometries are often challenging technologies to implement in the clinic and scaled manufacturing processes. Hydrogel injection molding capitalizes on the reproducibility, efficiency, and scalability of the injection molding process, and we adapt this technique to biofabrication using a library of natural and synthetic hydrogels with varied crosslinking chemistries and kinetics. We use computational modeling to evaluate hydrogel library fluid dynamics within the injection molds in order to predict molding feasibility and cytocompatibility. We evaluate the reproducibility of hydrogel construct molding and extraction and establish criteria for the selection of hydrogels suitable for injection molding. We demonstrate that hydrogel injection molding is capable of generating complex three-dimensional cell-laden construct geometries using diverse hydrogel materials and that this platform is compatible with primary human islet encapsulation. We envision the application of this technique with primary cells via an off-the-shelf clinical kit that can be implemented at the patient bedside by a clinician or integrated with scaled, high-throughput automated cell manufacturing processes to generate encapsulated cell-based therapeutic products. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/466681v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@fe1363org.highwire.dtl.DTLVardef@aae4c9org.highwire.dtl.DTLVardef@1927abaorg.highwire.dtl.DTLVardef@1b76af7_HPS_FORMAT_FIGEXP M_FIG C_FIG