Abstract Biologic scaffolds composed of naturally occurring extracellular matrix (ECM) have received significant attention for their potential therapeutic applications. The full potential of the ability of ECM scaffolds to promote constructive remodeling will not be realized, however, until an understanding of the biology and the external influences that affect biology, are better achieved. The factors that appear important for the constructive remodeling of ECM biologic scaffolds are its ability to be rapidly and completely degraded with the generation of downstream bioactive molecules, the bioinductive properties of the functional molecules that compose native ECM material and the ability to engineer its mechanical properties at the time of implantation through an understanding of its collagen fiber microstructure.