“…Early work from the late 1970s to early 1990s proved HD formation was dependent on implant bulk material, smooth surfaces promoted HD formation compared to rough surfaces, and adsorbed protein content controlled HD formation (a detailed history of these early studies may be found elsewhere.) [ [387] , [388] , [389] , [390] , [391] , [392] , [393] , [394] , [395] ] Parallel observations were being made from groups investigating implant osseointegration; osseointegration was dependent on implant material, rougher surfaces promoted osseointegration, and adsorbed protein content controlled osseointegration [ [396] , [397] , [398] , [399] , [400] , [401] , [402] ]. Since then, only a handful of studies have confirmed that physicochemistry and topography control HD in vitro [ 403 ] and in rat models [ 384 , [404] , [405] , [406] ], and specifically that HD formation (in rats at least) is generally higher on zirconia than titanium [ [407] , [408] , [409] ].…”