The Buffalo Bills are facing significant injury challenges as they head into the regular season, with key players including safety Damar Hamlin (hamstring), wide receivers Curtis Samuel (turf toe) and Marquez Valdes-Scantling (neck), and backup quarterback Mitchell Trubisky (knee) all listed as week-to-week. Coach Sean McDermott expressed concerns that some of these players may miss the season opener against Arizona on September 8. The Bills are already adjusting to a roster overhaul, having brought in 43 newcomers and only retaining 11 players from 2020. Additionally, linebacker Matt Milano is expected to miss at least the first few months of the season due to a torn bicep. McDermott has opted to sit all projected starters for the preseason finale and reduce practice time to manage the situation. This injury crisis could hinder the Bills' aspirations to improve upon their recent playoff performances.