Molecular Mechanism Study on Effect of Biodegradable Amino Acid Ester-Substituted Polyphosphazenes in Stimulating Osteogenic Differentiation.

Abstract

Amino acid ester substituted polyphosphazenes are osteoactive benefiting from their phosphorus-containing chemical structure, which highlights interests in bone tissue engineering. To correlate their chemical structures with cell activities, in this study, poly[(ethyl alanato)0.3 (ethyl glycinato)0.7 phosphazene] (PAGP) and poly[(ethyl phenylalanato)0.3 (ethyl glycinato)0.7 phosphazene] (PPGP) are synthesized to carry out studies on cell osteogenic differentiation. In the non-contact culture manner, bone mesenchymal stromal cells (BMSCs) are cultured in transwell chambers containing PAGP or PPGP films, while the cells and the materials do not contact. In the contact culture manner, BMSCs are cultured on the PAGP or PPGP films. In the meantime, solutions containing PAGP or PPGP degradation products (i.e., phosphate, ammonium, and corresponding amino acids) are applied for cell culture using inorganic phosphate (Pi) ion as control. Thus, the influences from substrate surface and degradation products can be identified separately. The results reveal that both the phosphorus-containing surface of PAGP and PPGP films and their degradation products play significant roles in regulating cell behaviors. In comparison with PAGP, PPGP seems able to provide relatively stable phosphorus-containing surface to strengthen the cell-scaffold interaction because of its slower degradation rate and higher Young's modulus, leading to greater promotion in osteogenic differentiation via contact effect.