He identified three novel components of the matrix, including a new subtype of collagen, which he labeled Type IV.
Initially, his conclusions were rejected by some of his contemporaries, but ultimately, he and his work were vindicated, and the field of research exploded. Now, 28 subtypes of collagen have been identified, said his son, Paul, also a physician. The elder Dr. Kefalides lectured internationally on his work.
Dr. Kefalides was born and raised in war-torn Greece. He immigrated to America in 1947 and settled in Chicago with his uncle.
In 1957, as a newly minted physician at the University of Illinois, Dr. Kefalides was drafted into the U.S. Public Health Service, for which he directed a research project in Lima, Peru, on the treatment of burn patients. At the time, the U.S. government was seeking to develop treatment plans for casualties in the event of nuclear war.
After returning to Chicago, he pursued studies that led to a doctorate in biochemistry while simultaneously completing his medical training in internal medicine and infectious diseases.
He worked as an academic physician and scientist at the University of Chicago before moving to Penn.
In 1977, with the closure of Philadelphia General Hospital, Dr. Kefalides' research labs moved to the University City Science Center, a biotechnology incubator connected to Penn and other medical schools.
He was director of the center's Connective Tissue Research Institute and a principal investigator using grant money from the National Institutes of Health.
For the next 25 years, he taught and mentored young scientists, medical trainees, and graduate students. When the institute closed in 2002, Dr. Kefalides became a mentor and consultant for the science center. He led an advisory committee and helped launch an interdisciplinary lecture series, "Lunch for Hungry Minds," which still exists.
To balance his scientific bent, Dr. Kefalides nurtured his love of languages: He spoke English, Spanish, and French, in addition to his native Greek. He was a stickler, his son said, about correct English grammar.
In later years, Dr. Kefalides wrote and self-published two memoirs - Echoes From the Cobblestones and Finding Aesculapius Across the Atlantic. The volumes chronicle his childhood in Greece and his experiences pursuing his education, becoming a naturalized American citizen, and starting a research career.
"Although he loved America for all of the opportunity it provided," his son said, "he remained faithful to his family and friends in Thessaloníki, and treasured spending his summer vacations along the seacoast in Greece."
Surviving, besides his son, are his wife, the former Jane Kutsunis; daughter Patty; three grandchildren; and a brother.
Services were Tuesday, Dec. 10.