Gaines had just returned from missing the previous two games with a concussion that he sustained in practice.
The absence of Gaines is especially troublesome for the Browns, who saw promising rookie Denzel Ward injure his hip during the first quarter of the contest. Ward was checked out in the sideline tent before he retreated down the tunnel.
Cleveland's secondary was short-handed as safety Damarious Randall was made inactive for the game.
Gaines, who signed with the Browns in March, had 12 tackles and one interception in five contests coming into Sunday's action.
The fifth-year veteran was a sixth-round pick of the then-St. Louis Rams in 2014 and missed the entire 2015 season with a Lisfranc injury. While with the Rams, he played under current Browns interim head coach Gregg Williams.
Gaines, who is listed at 5-foot-10 and 191 pounds, was traded to Buffalo as part of the Sammy Watkins deal last year and made 11 starts for the Bills. He had 59 tackles, an interception and three forced fumbles in those games.
The 26-year-old Gaines has recorded 197 tackles, four forced fumbles, two fumble recoveries and four interceptions in 42 career contests with the Rams, Bills and Browns.