Materials currently used for the treatment of bone defects include ceramics, polymeric scaffolds and composites, which are often impregnated with recombinant growth factors and other bioactive substances. While these materials have seen instances of success, each has inherent shortcomings including prohibitive expense, poor protein stability, poorly defined growth factor release and less than desirable mechanical properties. We have developed a novel class of amino acid-based poly(ester urea)s (PEU) materials which are biodegradable in vivo and possess mechanical properties superior to conventionally used polyesters (<3.5 GPa) available currently to clinicians and medical providers. We report the use of a short peptide derived from osteogenic growth peptide (OGP) as a covalent crosslinker for the PEU materials. In addition to imparting specific bioactive signaling, our crosslinking studies show that the mechanical properties increase proportionally when 0.5% and 1.0% concentrations of the OGP crosslinker are added. Our results in vitro and in an in vivo subcutaneous rat model show the OGP-based crosslinkers, which are small fragments of growth factors that are normally soluble, exhibit enhanced proliferative activity, accelerated degradation properties and concentration dependent bioactivity when immobilized.