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

Abstract

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 nanocomposites calcium was substituted with strontium to the extent of 25, 50, 75 and 100mol% by substituting the CaCl₂-stock solution (0.1M) with SrCl₂ (0.1M) 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 (Sr₅(PO₄)₃OH, SrHA). The formed mineral phases were characterized by transmission electron microscopy (TEM) and RAMAN spectroscopy. All collagen/mineral nanocomposites 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 28days reached 141.2μg (~27μgmg^-1) from Sr50 and 266.1μg (~35μgmg^-1) from Sr100, respectively. Under cell culture conditions this led to maximum Sr²⁺ concentrations of 0.41mM (Sr50) and 0.73mM (Sr100) measured on day 1, which declined to 0.08mM and 0.16mM, 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.

Keywords: Biomimetic; Collagen; Fibril formation; Mineralization; Nanocrystalline hydroxyapatite; Osteoporosis; Scaffolds; Strontium.