A review of the structural and physical properties that govern cell interactions with structured biomaterials enabled by additive manufacturing

Additive manufacturing (AM) encapsulates a suite of enabling materials processing platforms that can yield the hierarchical complexity intrinsic to biologically functional tissues with applications in regenerative medicine, physiological and disease modeling, drug testing, and organ-on-a-chip platforms. Engineered tissues consist of two primary constituents, namely cells and biomaterials. Generally, the processability, cytocompatibility, and structural integrity of the biomaterials converge to influence the extent to which engineered tissue constructs can meet the functional demands of in vivo tissue. Specifically, the structural and physical properties of tissue constructs at distinctive well-defined range of length scales and parameter magnitudes are expected to differentially affect the cell-biomaterial interactions (CBI). Based on this premise, this review is appropriately scoped to survey the most recent and relevant literature on CBI, specifically within the context of well-defined structural and physical material property measurements for 3D structured materials or scaffolds based on prevailing AM technologies, biomaterials, and tissue types. Moreover, the organizational nomenclature used in the review uniquely classifies and presents CBI based on small, intermediate, and large pore size features and material feature size, along with high and low elastic modulus and swelling ratio, microscale/nanoscale physical surface topology, as well as densely and sparsely charged chemical surface properties. This convergence and distillation of the literature into clearly delineated properties will enable the biomanufacturing community to gain fundamental insight into the effect of printed structural and physical outcomes within the various parameter magnitude ranges on the downstream biological measurement outcomes. As a result, both the biomanufacturing researcher and practitioner would be able to narrow the parameter and material design space towards predicting and implementing the window of AM process parameters in which the desired biological outcomes can be realized.