Strontium-modification of porous scaffolds from mineralized collagen for potential use in bone defect therapy

The present study describes the development and characterization of strontium(II)-modified biomimetic scaffolds based on mineralized collagen type I as potential biomaterial for the local treatment of defects in systemically impaired (e.g. osteoporotic) bone. In contrast to already described collagen/hydroxyapatite nano composites calcium was substituted with strontium to the extent of 25, 50, 75 and 100 mol% by substituting the CaCl2-stock solution (0.1 M) with SrCl2 (0.1 M) during the scaffold synthesis. Simultaneous fibrillation and mineralization of collagen led to the formation of collagen-mineral nanocomposites with mineral phases shifting from nanocrystalline hydroxyapatite (Sr0) over poorly crystalline Sr-rich phases towards a mixed mineral phase (Sr100), consisting of an amorphous strontium phosphate (identified as Collin's salt, Sr6H3(PO4)(5) * 2 H2O, CS) and highly crystalline strontium hydroxyapatite (Sr-5(PO4)(3)OH, SrHA). The formed mineral phases were characterized by transmission electron microscopy (TEM) and KAMAN spectroscopy. All collagen/mineral nano composites with graded strontium content were processed to scaffolds exhibiting an interconnected porosity suitable for homogenous cell seeding in vitro. Strontium ions (Sr2+) were released in a sustained manner from the modified scaffolds, with a clear correlation between the released Sr2+ concentration and the degree of Sr substitution. The accumulated specific Sr2+ release over the course of 28 days reached 141.2 mu g (similar to 27 mu g mg(-1)) from Sr50 and 266.1 mu g (similar to 35 mu g mg(-1)) from Sr100, respectively. Under cell culture conditions this led to maximum Sr2+ concentrations of 0.41 mM (Sr50) and 0.73 mM (Sr100) measured on day 1, which declined to 0.08 mM and 0.16 mM, respectively, at day 28. Since Sr2+ concentrations in this range are known to have an osteo-anabolic effect, these scaffolds are promising biomaterials for the clinical treatment of defects in systemically impaired bone.