Impact of graft architecture of PEGylated copolymers assembly on hydroxyapatite in the differential regulation of initial cell and bacterial adhesion

Synthetic pure hydroxyapatite (HA), though widely investigated as an artificial orthopedic implant material, has neither anti-infection properties nor innate interfacial bioactivity. Ideally, surface modification of this material needs to be developed with simultaneous anti-microbial capacity and superior cytocompatibility. Herein, graft copolymers of a PAA backbone functionalized with a high density of polyethylene glycol (PEG), and varying grafting densities of cyclic Arg-Gly-Asp-d-Phe-Cys peptides (cRGD) end-grafted onto the PEG chains have been designed and synthesized. Systematic study on the grafted anchoring groups first indicates a synergistic binding mechanism of the copolymer to HA surface, involving electrostatic interaction of the protonated amino (–NH 3 + ) with negatively charged HA, assisted with coordination bonding through the nitrodopamine (ND) group. The PEGylated graft copolymers are demonstrated to firmly adsorb to the HA surface as an ultrathin self-assembly layer from a HEPES buffer solution, showing stability with insignificant desorption and effective inhibition of non-specific protein adsorption evaluated by XPS and QCM-D assays. Direct adhesion assays confirm that HA, modified with the density-optimized cRGD/PEG-functionalized graft polymer, can considerably promote osteoblast attachment, while preventing different strains of bacteria adhesion in the initial phase.