Osteogenic Differentiation of Rat Bone Marrow Mesenchymal Stem Cells Regulated by Varying the Phosphorylation of Polymers
Bone defects remain a prevalent clinical challenge, and regenerative medicine based on bone tissue engineering offers promising solutions. Traditional osteogenic materials rely on bioactive macromolecules like growth factors, which suffer from poor stability and stringent storage requirements. From a structural perspective, bone tissue resides in a phosphorylated microenvironment, with 65–70% of inorganic components composed of hydroxyapatite. Inorganic phosphorylated materials induce osteogenic differentiation but exhibit high stiffness, brittleness, slow degradation, and limited mechanical tunability. Synthetic phosphorylated polymers with excellent mechanical properties and biocompatibility have been developed to address these issues. In this work, we developed a series of phosphorylated polymers derived from poly(glycerol sebacate) (PGS), a biocompatible and biodegradable material. Leveraging the hydroxyl-rich backbone of PGS, we demonstrated an efficient method for controllable phosphorylation of PGS side chains, enabling synthesis of PGS-based phosphorylated (PGS-P) polymers with tunable phosphorus contents. The optimized phosphorylated polyester, PGS-P4, exhibited strong ability to promote osteogenic differentiation of rat BMSCs, and its porous three-dimensional scaffolds showed favorable properties for bone regeneration. BMSCs cultured for one week and observed by fluorescence microscopy showed enhanced BSP protein expression on PGS-P2, PGS-P4, and PGS-P6 groups compared with PLGA and PGS, with PGS-P4 displaying the most intense signal. In summary, we present a simple and controllable method for preparation of functionalized polyesters and their porous scaffolds with tunable phosphorus content, validating its effectiveness in promoting osteogenic differentiation of rat BMSCs. All phosphorylated polyesters exhibit enhanced differentiation-promoting effects compared to non-phosphorylated PGS; however, the degree of enhancement does not increase monotonically with phosphorus content. PGS-P4, containing an optimal phosphorus level, shows the most pronounced biological functions.