Biomaterial microarchitecture: a potent regulator of individual cell behavior and multicellular organization

Insoluble cues from a cell's surrounding microenvironment have increasingly been shown to be important regulators of cell behavior. The microarchitecture of biomaterials used for 3D cell encapsulation, however, is often underappreciated as an important insoluble factor guiding cell activity. In this review, we illustrate that the subcellular physical features of a scaffold influence a range of cell behaviors, including morphology, cytoskeletal organization, migration, matrix remodeling, and long-range force transmission. We emphasize that the microarchitecture of stromal extracellular matrix (ECM)-specifically the fact that it consists of a network of long interconnecting fibers with micron and nanometer-sized diameters-is an important determinant of how cells naturally interact with their surrounding matrix and each other. Synthetic biomaterials with a microarchitecture similar to stromal ECM can support analogous cellular responses, suggesting that this fibrous microarchitecture is a key regulator of these cell behaviors. Drawing upon examples from in vitro, in silico, and in vivo studies, we compare these behaviors in fibrous matrices to those of cells cultured within nanoporous matrices (e.g., alginate and PEG gels) as well as macroporous scaffolds to highlight key differences in the cellular response to each type of microarchitecture. Understanding how microarchitecture affects cell behavior can lead to more efficient biomaterial selection when designing tissue engineered scaffolds for therapeutic applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 640-661, 2017.