This article presents a strategy for design, engineering, and fabrication of a bioresorbable, manufactured bone graft substitute (BGS) device. The approach is based on established precepts of osteogenesis, molecular biology of hyaluronic acid and osteoinductive proteins, and theoretical preformance criteria for such a device collated from the literature of 1991 to 1996. Application of this design and engineering strategy results in a composite device consisting of a D,D-L,L-polylactic acid macrostructure optimized to the architecture of cancellous bone, a microstructure composed of a filamentous velour of hyaluronan and a recombinant human bone morphogenetic protein 2 (rhBMP-2). The performance of this construct was tested in vivo in the dog, intertransverse process, spinal fusion model and in a critical sized defect of the rabbit radius. Data from these studies are used to illustrate principle points of the design and engineering concept.