This grant provides the first year of funding for tissue engineering research that aims to determine relationship between bone ingrowth, initial scaffold microstructure and properties, and scaffold/tissue composite properties. Specifically, it aims to answer the question: How does the percent bone fill in the scaffold after tissue regeneration and the scaffold/tissue composite properties correlate with initial mechanical properties, and more fundamentally with the initial microstructure of the scaffold? For the initial study, a design space will be constructed in vitro that represents the range of possible mechanical properties for the scaffold/tissue composites. Hydroxyapatite (HA) scaffolds with four different microstructures, but all with the same macrostructure, will be infiltrated with hard and soft polymers, representing 100% bone and connective tissue fill, respectively. Composite scaffolds will be tested in compression and will provide a set of upper and lower bounds on mechanical properties for each microstructure. The results from the in vitro study will feed into a future in vivo study; a subset of the microstructures examined will be implanted into a swine mandible and evaluated for bone ingrowth and composite mechanical properties. The research has the potential to make significant advances in the fundamental understanding of the structure-property relationships of bone scaffolds. The clinical and societal impact for the research is evident. There are people who are in need of massive scales of bone reconstruction including, for example, the elderly, those afflicted with oral cancer, or who have suffered blunt force trauma like the American soldiers injured in Iraq. There are no appropriate products on the market to fill this need; therefore, results derived from this work have the potential to significantly improve the quality of life for patients with critical-sized bone defects.