Willis was placed on the season-ending injured reserve list Tuesday for the injury suffered in the third quarter at St. Louis on Oct. 13.
"It's very frustrating," Willis said. "My teammates mean everything to me and I want to be out there experiencing all the good times and all the rough times with them."
A Pro Bowler all seven seasons in the NFL, Willis had missed six games in his career before this latest injury sidelined him for the final 10 games in 2014 for San Francisco (5-4). He had 34 tackles and an interception this season for the 49ers.
Smith is set to begin practicing this week after serving a nine-game suspension by the NFL for violations of the league's substance-abuse and personal-conduct policies.
In addition, 2013 All-Pro linebacker NaVorro Bowman could be cleared to begin practice this week, opening a 21-day window for the team to activate him or place him on IR.
Bowman is recovering from surgery on his left knee after he tore the anterior cruciate and medial collateral ligaments in a devastating injury in the NFC championship game loss at Seattle last January.
Mebane's loss is a blow to Seattle's run defense, which ranks fourth in the league at 79.8 yards per game.
The Chicago Bears waived former Super Bowl most valuable player Santonio Holmes.
The receiver signed a one-year deal with Chicago in August after being released by the New York Jets in March. He had eight receptions for 67 yards along with nine punt returns for 50 yards.
Josh Brent is a big step closer to playing football again, almost two years after a drunk-driving crash that killed a teammate and led to his conviction for intoxication manslaughter.
The Dallas defensive tackle was activated Tuesday, a day after the end of a 10-game suspension imposed by the NFL when he was reinstated before the season.
Coach Jason Garrett said Brent, listed at 320 pounds, was overweight and didn't indicate whether he would be ready for the Cowboys' next game Nov. 23 at the New York Giants. Dallas has its bye this week.
The 26-year-old Brent's last game was Dec. 2, 2012, six days before the crash that killed teammate Jerry Brown in the Dallas suburb of Irving. He has been practicing for two weeks.