Protein biomaterial systems for tissue engineering strategies

Improved understanding of matrix‐cell interactions has provided new direction to the design and study of biomaterial scaffolds to direct cell and tissue outcomes in vitro and in vivo. The ability to deliver appropriate topography, structure and chemistry to cells to direct their fate is emerging as a useful strategy relevant to functional tissue formation. Toward this goal, we utilize fibrous protein scaffold systems (e.g., collagens, silks) and control material features during biosynthesis, assembly, processing and functionalization. Specific examples of cell‐material interactions and outcomes include rates and modes of protein scaffold remolding related to protein structure, protein matrix structure related to control of stem cell fate, protein matrix designs for the delivery of cell signaling factors, and genetically tailored protein matrix designs to add functional features to regulate cell function via scaffold signaling. In these cases, the ability to tailor the protein matrix structure, morphology or chemistry leads to new insight into modes to control cell fate, and thus tissue outcomes. The control of these features also mimics, to some extent, the information context found in cell‐matrix communication in native tissues, in abnormal tissues or in tissue development. Thus, highly controlled matrix designs offer new options with which to gain insight into tissue regeneration, disease states and many related areas of biomedical need such as drug discovery. Our specific areas of interest include hard and soft tissue regeneration. In most cases, different human stem cell sources are utilized in defined bioreactor environments to engage with the matrix‐cell interface toward desired functional tissue outcomes. Specific examples of tissue systems will be reviewed, along with current strategies aimed at understanding and utilizing vascularization in these systems to improve functional outcome. Disease models will also be discussed in the context of matrix design and cell signaling requirements.