Pagano said Wayne's biggest regret is that he won't be around to help his young teammates chase a championship.
At 5-2, the Colts lead the AFC South by two games heading into their bye week. Only Kansas City (7-0) and Denver (6-1) have better records in the conference overall.
Indianapolis will be back on "Sunday Night Football" for a Nov. 3 trip to Houston after the bye, and the team is being treated as a serious Super Bowl contender after wins against the Broncos, Seahawks and 49ers.
But Wayne's injury cast the immediate future in doubt.
Pagano said his players will respond as they always have to adversity, by working even harder to overcome it.
"That group in that (wide receivers) room, you just watch how they play," he said. "Because when you lose a family member, we're tight as it is, but this will make us even stronger. It'll make that room even stronger. And they have a responsibility, and they're accountable to one another. They'll go out and they'll play better than they've ever played for 87."