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Sheffield United manager Chris Wilder has said striker Ryan One is facing "a number of weeks" on the sidelines with a hamstring injury.
The 20-year-old initially suffered the problem in the 0-0 draw with Birmingham in August and was out for two months.
The Scotland Under-21 international returned as a substitute in the wins over Lincoln and Bristol City earlier this month but aggravated the issue in training last week.
"We've had some disappointing news regarding Ryan. It was the same spot he got the initial injury, so he is going to be out for a number of weeks," Wilder told BBC Radio Sheffield.
"All of our supporters understand the importance of him. He was great for us in the Bristol City and Lincoln games when he came on.
"It's a disappointing one because we're ready for Ryan to make an impact, whether that's off the bench or starting."
Wilder is hopeful striker Patrick Bamford will be available for Friday's game against Wrexham (20:00 GMT) after being forced off with a shoulder injury in the draw with Derby on Saturday.
Defender Mark McGuinness will return to the squad for the game against the Red Dragons after missing the Rams draw because of concussion protocol.