The present study sought to demonstrate the swelling behavior of hydrogel-microcarrier composite constructs to inform their use in controlled release and tissue engineering applications. In this study, gelatin methacrylate (GelMA) and GelMA-gelatin microparticle (GMP) composite constructs were three-dimensionally printed, and their swelling and degradation behavior was evaluated over time and as a function of the degree of crosslinking of included GMPs. GelMA-only constructs and composite constructs loaded with GMPs crosslinked with 10 mM (GMP-10) or 40 mM (GMP-40) glutaraldehyde were swollen in phosphate-buffered saline for up to 28 days to evaluate changes in swelling and polymer loss. In addition, scaffold reswelling capacity was evaluated under five successive drying-rehydration cycles. All printed materials demonstrated shear thinning behavior, with microparticle additives significantly increasing viscosity relative to the GelMA-only solution. Swelling results demonstrated that for GelMA/GMP-10 and GelMA/GMP-40 scaffolds, fold and volumetric swelling were statistically higher and lower, respectively, than for GelMA-only scaffolds after 28 days, and the volumetric swelling of GelMA and GelMA/GMP-40 scaffolds decreased over time. After 5 drying-rehydration cycles, GelMA scaffolds demonstrated higher fold swelling than both GMP groups while also showing lower volumetric swelling than GMP groups. Although statistical differences were not observed in the swelling of GMP-10 and GMP-40 particles alone, the interaction of GelMA/GMP demonstrated a significant effect on the swelling behaviors of composite scaffolds. These results demonstrate an example hydrogel-microcarrier composite system's swelling behavior and can inform the future use of such a composite system for controlled delivery of bioactive molecules in vitro and in vivo in tissue engineering applications. Impact statement In this study, porous three-dimensional printed (3DP) hydrogel constructs with and without natural polymer microcarriers were fabricated to observe swelling and degradation behavior under continuous swelling and drying-rehydration cycle conditions. Inclusion of microcarriers with different crosslinking densities led to distinct swelling behaviors for each biomaterial ink tested. 3DP hydrogel and hydrogel-microcarrier composite scaffolds have been commonly used in tissue engineering for the delivery of biomolecules. This study demonstrates the swelling behavior of porous hydrogel and hydrogel-microcarrier scaffolds that may inform later use of such materials for controlled release applications in a variety of fields including materials development and tissue regeneration.
Keywords: 3D printing; biomaterial ink; hydrogel; microcarrier; microparticle; multiphasic scaffold.