Engineering scaffold and soluble cues for cell-instruction

Abstract

In this work, we examined the use of microenvironmental scaffold cues and soluble factor cues for cell-instruction. Collagen-based scaffolds were modified through various approaches to generate a range of stiffness. These scaffolds were further used to regulate the malignancy of hepatocellular carcinoma cells and phenotype of fibroblasts. In addition, we also fabricated stiff and metastable hydrogels for the release of soluble factors in vivo. The high stiffness of the unique material, allowed the release of encapsulated substances independent of local tissue pressures. The decoupled control of stiffness and degradation rate was also achieved by tuning the composition of the hydrogel. This system was successfully used as an injectable depot for controlled release in porcine models. The separate investigations of microenvironmental scaffold cues and soluble factors cues covered in this work would provide an important stepping stone for the subsequent combination of these cues in integrated tissue regeneration and cell-instructive applications.