Protein-based drugs are increasingly used to treat bone disorders, kidney disease, wounds, arthritis and cancer. But the proteins frequently degrade, limiting their therapeutic potential and sometimes causing immune reactions.
UW-Madison scientists, inspired by proteins found intact in centuries-old human bones, created a mineral coating that mimics bone and appears to keep proteins stable.
“What’s needed is a delivery system that remains localized, releases the protein over an extended time frame and keeps the protein active,” said William Murphy, a UW-Madison professor of biomedical engineering.
Murphy and his colleagues, including Xiaohua Yu of the UW School of Medicine and Public Health, reported on their mineral coating — constructed at the miniature level of biology known as the nanoscale — in this week’s edition of the journal Advanced Materials.
In a lab dish, the mineral coating released a protein, called basic fibroblast growth factor, which remained active for more than a month. When the protein was released by a commonly used system made with polymers, or plastics and rubber, it stayed active for less than a week.
In rabbits, the scientists repaired Achilles tendon tears by stitching together the severed portions of the tendon. Sutures lined with mineral coating that released two growth factors healed the injury better than regular sutures, Murphy said.
Even after the mineral coatings were subject to harmful solvents in the lab dish and sterilization of the sutures — conditions that can cause proteins to degenerate — the proteins remained intact.
“We really can hit these proteins with a sledgehammer, so to speak,” and they remain protected by the mineral coating, Murphy said.
Emu’s egg was a ‘trigger’
Murphy and his colleagues knew about archaeological discoveries of growth factors and other proteins preserved in human teeth and bones from the Middle Ages. But it was a 2010 report about DNA extracted from a 19,000-year-old emu eggshell in Australia that really gave him the idea for medical applications.
“It triggered a greater interest in how powerful these calcified tissues can be for stabilizing biologic molecules,” said Murphy, co-director of UW-Madison’s Stem Cell and Regenerative Medicine Center. “If we could recreate some critical aspects of mineralized tissues, they may serve as a template for protein stabilization.”
He and his team created the coating by soaking a special surface in a solution containing mineral ions found in human blood, and growing crystals. “It’s not all that different from a really simple crystal growth kit that a grammar school student might buy,” he said.
The scientists are now using the mineral coating in rodent studies of protein therapies for rheumatoid arthritis.
Other applications could include knee and hip implants and drugs for cancer, wounds and bone disorders. The system might also help improve drugs such as erythropoietin, or EPO, used to boost red blood cells damaged by kidney disease. The drug’s unstable proteins can cause immune system reactions.
If proteins could be better stabilized in drug delivery, patients might need injections only once every month or two instead of every day or week, Murphy said.