Phosphoserine (Pser), the phosphorylated amino acid highly abundant in Non-collagenous proteins (NCPs), and small molecules such as citrate are integral part of bone matrix and play important regulatory roles at the organic/inorganic interface for controlled bone cell activity and mineralization. Therefore, to better mimic the native bone, we incorporated Pser into citrate-presenting polymers to develop a new biomimetic biodegradable photoluminescent polymer, BPLP-Pser via a convenient polycondensation reaction. The incorporation of Pser in the polymer was confirmed by <sup>31</sup>P NMR in combination with HPLC. BPLP-Pser showed excellent photoluminescence properties, such as tunable emission and excellent photostability. The incorporated Pser was found to promote the nucleation of calcium phosphate in an in vitro mineralization test and to further improve its cytocompitability. Moreover, hMSCs cultured on BPLP-Pser films showed improved osteogenesis evidenced by elevated alkaline phosphatase (ALP) production and increased gene expression of Runx2 and osteopontin (OPN). BPLP-Pser-HA composite microparticles (MPs) were prepared and mixed with hMSCs. The Mps act as a scaffold to support the proliferation, differentiation, and mineralization of the seeded hMSCs in a 3D manner to form integrated cell-MPs constructs. Homogenous cell distribution was observed within the cell/particle construct. Further, hMSCs on BPLP-Pser-HA MPs was found to differentiate with sustained and elevated ALP expression, which was ascribed to a synergistic effect of Pser and citrate on osteogenesis. In a rat femoral condyle defect model, the implanted BPLP-Pser-HA MPs provided an interconnective 3D framework allowing successful tissue growth around the implant and throughout the defect. Moreover, the osteogenic activity of bone-forming cells in BPLP-Pser-HA group was significantly elevated evidenced by an enhanced ALP and osteocalcin (OCN) expression, which led to extensive peri-implant bone formation and increased bone mineral density (BMD). In conclusion, BPLP-Pser-HA composite microparticles may serve as a promising scaffold for orthopedic engineering.

Biomimetic biodegradable photoluminescent polymers for bone tissue engineering

254th National Meeting (2017)

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