Although several strategies have been undertaken in the past decade to produce clinically effective engineered bone tissues, the resultant materials have exhibited only a limited ability to stimulate tissue integration, vascular infiltration, and remodeling in vivo relative to autograft materials. We postulate osteoprogenitor cells may be an effective component in the ex vivo development of engineered bone tissue, but recognize that the cell microenvironment must be conducive to the deposition of osteogenic and angiogenic extracellular matrix. One component of this microenvironment that has not been addressed to date is the compressive modulus of the biomaterial scaffold. To test the effect of scaffold modulus on osteoblastic differentiation we have synthesized a family of novel degradable, biocompatible, high-modulus segmented polyurethanes. Our polyurethanes consist of a polycaprolactone (PCL) soft segment and a tyramine-1,4-diisocyanaobutane-tyramine (TyA.BDI.TyA) containing hard segment. By systematically varying the PCL molecular weight and the polymer stoichiometry, we have achieved a family of polymers with similar chemistries, but with different mechanical properties due to differences in hard segment content and the degree of microphase separation. We have already shown storage moduli of 50 to 300 MPa for different PCL diol molecular weights and that all materials support cell proliferation and development of the osteoblastic phenotype.

Here, we present physical and biologic analyses of our porous polyurethane scaffolds. Materials were processed into porous foams by compression molding/particulate leaching and porosity and compressive modulus were measured. We also generated degradation profiles of the polyurethane scaffolds over 16 weeks. Finally, proliferation of BMSCs and levels of markers of osteoblastic differentiation including osteopontin, bone siloprotein, and osteocalcin were measured as well as the angiogenic factor, VEGF-A.