Table 3.

Summary of the cell/protein and surface interactions, as reported in literature

Property	Protein response	Cell response	Refs
Wettability	Hydrophobic surfaces promote stronger association, but hydrophilic surfaces are suggested to induce a better quality of the protein layer. VEGF domains on FN exposed only on hydrophilic surfaces.	Lower attachment to hydrophobic surfaces.	[120, 185, 223, 240, 241, 246]
Roughness	Proteins respond to nanoscale features. Roughened surfaces entrap more proteins and expose more surface area for attachment.	Increased surface area allows for more binding sites. Increased cell attachment was detected on organized rough surfaces as opposed to disorganized surfaces. Cells require a certain roughness ratio to allow for appropriate positioning of the integrin clusters necessary for anchorage to the surface.	[226, 250–254, 256, 257, 262, 263]
Geometry	Grooves increase the surface area available for attachment.	Grooves increase the surface area available for attachment and have been found to align cells. Vascular smooth muscle cells and ECs favour aligned grooves	[258]
Grain size	Effect depends on protein type (mainly protein size) and the impact of grains on the surface roughness. The reduction in grain size is often associated with increased surface roughness which generally results in better attachment.	Effect depends on cell type and the impact of grains on the surface roughness.	[265, 266]
Grain boundaries	Increased number of grain boundaries may increase the surface roughness increasing the surface area exposed to proteins.	Increased ion dissolution found at grain boundaries is associated with better osseointegration.	[151, 152]
Surface modification and composition	Incorporation of silicon ions into the HA lattice may improve protein attachment.	Loading surfaces with bioactive agents such as heparin can improve cell osteogenesis and angiogenesis.	[274, 275]
Charge	Protein orientation and unfolding as a result of the localized protein and surface charge are believed to dictate the quality of the attachment.	Positive surfaces may attract cells due to their negative cell membrane but the overall cell attachment and behaviour appears to be more strongly modulated by the protein response to the surface charge.	[276, 277, 280]