Enhancement of osteoblast cells osteogenic differentiation and bone regeneration by hydroxyapatite/phosphoester modified poly(amino acid).

Hydroxyapatite/poly(amino acid) (HA/PAA) has been used to treat a variety of long bone and vertebral bony defects, and a further biocompatibility improvement is a key for better application. Phosphoester (PE) contained materials are highly biocompatible but could hardly treat massive bone defects due to its fast-degradation-derived mechanical instability. To address the problems of the two materials, we have incorporated PE molecule into the main chain of PAA by chemical bonding. As a result, the compressive strength of HA/PAA with 1 wt% and 2.5 wt% PE maintained in the range of 80-150 MPa after soaking in PBS for 12 weeks, which could be attributed to the amplified hydrogen-bonding inside composites. Besides, the PE-containing HA/PAAs with increased hydrophilic function groups (O=P-O bonds and O=P-N), created a more favourable surface for cell adhesion. Meanwhile, compared with HA/PAA, the PE-containing HA/PAAs had a fast minerlization speed and promoted cell osteogenic differentiation. Furthermore, the in vivo study indicated that PE-containing HA/PAAs could facilitate bone formation (4 weeks), and form a complete bone bridging (12 weeks) in a rabbit cranial bone defect. In summary, the HA/PE-m-PAAs possessed good mechanical stability, improved cytocompatibility and osteoconductivity, so the composites have a great potential for massive bone defect treatment.