At the Grotto, Pope Francis was greeted by Sister Mary Scullion of Philadelphia's Project HOME.
While there, the pope blessed the 100,000 strips of white paper, bearing people's troubles and worries, which were tied to the display.
"He asked us to pray for him and, of course, we asked him to pray for us and bless the knots," said Sister Scullion.
Also present at the Grotto was an excited group of volunteers from Saint Joseph's University who captured the spiritual moment on their cell phones.
"You think it would be like a celebrity moment or something, but it was just so much more than that because we connect with him so much," said Theresa Ta, a student.
"I thought this was the most amazing moment of my life. I saw God there and we're all here together, a Saint Joe's community, which is the most beautiful thing ever," said student Asha Jacobs.
Earlier in the day, the pope surprised the students with a visit at the university.
The interactive sculpture is inspired by the painting "Mary, Undoer of Knots," a favorite of the pope's.
Tens of thousands of people have submitted ribbons with prayers to be attached to the structure.