合成マトリックスにおける粘弾性媒介細胞リモデリングを可能にする超高速緩和・光重合性PEGヒドロゲル

Synthetic hydrogels provide powerful material platforms to engineer cellular microenvironments with control over stiffness, viscoelasticity, porosity, degradability, and biochemical signals. Here, we demonstrate how orthogonal crosslinking reactions allow fabrication of covalent adaptable networks to tailor photopolymerizable bioresin formulations relevant for tissue engineering. Specifically, we synthesize multifunctional poly(ethylene glycol) (PEG) macromers containing dynamic boronate ester bonds and dithiolane and norbornene moieties that allow for photopolymerization and projection-based biofabrication. These materials are used to print human mesenchymal stromal cells (MSCs) in formulations where the ratio of elastic versus adaptable crosslinks is engineered to study and manipulate MSC spreading, actin structure, and macroscopic material-level deformation. We demonstrate how material and print parameters, peptide ligands, actomyosin-modulating drug treatments, and cell types influence cell-material interactions and emergence of morphogenesis that is uniquely enabled by viscoelasticity. The presented materials introduce a versatile strategy for spatiotemporal control over dynamic mechanical properties in cell-laden matrices.