Engineering a collagen matrix for cell-instructive regenerative angiogenesis

Engineering an angiogenic material for regenerative medicine requires knowledge of native extracellular matrix remodeling by cellular processes in angiogenesis. Vascularization remains a key challenge in the field of tissue engineering, one that can be mitigated by developing platforms conducive to guiding dynamic cell-matrix interactions required for new vessel formation. In this review, we highlight nuanced processes of angiogenesis and demonstrate how materials engineering is being used to interface with dynamic type I collagen remodeling, Notch and VEGF signaling, cell migration, and tissue morphogenesis. Because alpha 1(I)-collagen is secreted by endothelial tip cells during sprouting angiogenesis and required for migration, collagen is a very useful natural biomaterial and its angiogenic modifications are described. The balance between collagen types I and IV via secretion and degradation is tightly controlled by proteinases and other cell types that are capable of internalizing collagen to maintain tissue integrity. Thus, we provide examples in skin and cardiac tissue engineering of collagen tailoring in diverse cellular microenvironments for tissue regeneration. As our understanding of how to drive collagen remodeling and cellular phenotype through angiogenic pathways grows, our capabilities to model and manipulate material systems must continue to expand to develop novel applications for wound healing, angiogenic therapy, and regenerative medicine.