Phosphorylated Polymers For Bone Tissue Engineering

Non-union bone defects have no satisfactory clinical solutions. Bone tissue engineering provides a promising approach to address this challenge. Scaffold materials which can induce stem cells differentiation are the key to this approach, especially in emerging cell-free in situ bone regeneration. Biomimetic materials that can mimic the structure and function of the native bone matrix are expected to be part of the next generation of materials. Among these, phosphorylated materials are an important class because bone is a highly phosphorylated tissue.Here, we design, prepare and characterize a series of biodegradable phosphorylated polymers and their corresponding scaffolds. We systematically investigated the interactions between materials and bone mesenchymal stem cells(BMSCs) and/or osteoblasts. The thesis includes following two parts:(1) Design, sysnthesis, and properties of phosphorylated polyester, poly(sebacoyl diglyceride) phosphate(PSe D-P). The backbone PSe D was synthesized based on acid-induced epoxide ring-opening polymerization, recently developed in our group, in two steps. Then the direct phosphorylation of PSe D using phosphorus oxychloride under low temperature efficiently produced PSe D-P. Gel permeation chromatography(GPC), nuclear magnetic resonance(NMR), attenuated total reflection infrared spectroscopy(ATR-FTIR), inductively coupled plasma atomic emission spectra(ICP-AES), the air-water contact angle measurement were used to characterized its structure, composition, and physicochemical properties. The porous PSe D-P scafold was prepared via salt-leaching method, and characterized by ICP-AES, thermogravimetic analysis(TGA), differential scanning calorimetry analysis(DSC) and compression tests. Then the 2-dimension and 3-dimension interactions between PSe D-P and osteoblasts and BMSCs were investigated. It demonstrated that PSe D-P promoted the adhesion, proliferation, and maturation of osteoblasts and, the osteogenetic differentiation and extracellular matrix(ECM) mineralization.(2) Design, sysnthesis, and properties of a series of poly(glycerol sebacate) phosphate(PGS-P) with varying contents of phoshphate groups. The backbone of these polymers is PGS, a widely used biomaterial. Direct phosphorylation of PGS using phosphorus oxychloride based on the mehtod developed in first part readily produced PGS-P. Varying the feeding ratio of phosphorus oxychloride efficeintly controlled the content of phosphate groups in PGS-P. GPC, NMR, ATR-FTIR and ICP-AES were used to characterize their structures. The air-water contact angle measurements were used to evaluate its hydrophilicity. The porous PGS-P scafolds were prepared via salt-leaching method. The thermal properties of scaffolds were characterized by TGA and DSC, Simple and cyclic compression tests were used to evaluate its mechanical properties. The in vitro degradadtion of PGS-P scaffolds were investigated as well. The studies on the 2-dimenstion interaction between PGS-Ps and BMSCs revealed that the contents of phosphate groups in PGS-P had significant effects on the cell behaviors. In summary, we designed and synthesized a series of biodegradable potentially osteoinductive polymers with controlled phosphorated groups. These provide new biomaterials for bone tissue engineering. Our studies revealed that these phosphorylated polymers modulated the cell behaviors in a phosphorous concentration-dependent manner, and modorate content of phosphate groups was in favor of promoting osteogenesis. This insight provides a reference for future design of osteoinductive biomaterials.