For most fractures, bones naturally heal as cells regrow while a cast or brace keeps the injury stable. However, in complex or severe cases, surgeons often use grafts, scaffolds made from biocompatible materials, or metal fixation devices to ensure proper healing and alignment.
In collaboration with orthopedic surgeons, biomedical engineering researchers at Penn State have developed CitraBoneQMg, an innovative biodegradable scaffold designed to accelerate bone repair. This implant combines magnesium and glutamine with citric acid, creating a bioactive material that supports bone regeneration. Their findings, published in Science Advances, are the basis of a U.S. patent application.
“By integrating magnesium and glutamine—nutrients naturally found in the body and food—into a citric acid–based scaffold, we discovered that these molecules work together to boost bone cell growth by enhancing intracellular energy metabolism,” explained Hui Xu, lead author and doctoral student in biomedical engineering, advised by co-corresponding author Su Yan, assistant research professor.
The team found that supplementing a traditional citric acid–based implant (already FDA-approved and commercially available) with magnesium and glutamine not only increased intracellular energy but also regulated two critical energy pathways for bone growth: AMPK and mTORC1. Normally, these pathways act in opposition, but within the scaffold they were harmonized, supplying stem cells with the energy required to grow and differentiate into bone cells.
“Instead of working like a seesaw, the pathways were activated together,” Xu said. “This synergy essentially supercharges bone cells, giving them more energy to regenerate and resulting in stronger bone regrowth.”
To evaluate CitraBoneQMg, researchers implanted it into cranial defects in rats and compared healing with both citric acid–only scaffolds and traditional bone graft materials. After 12 weeks, bone growth around the defect increased by 56% compared with citric acid–only scaffolds and by 185% compared with conventional bone implants.
“The three components act as a healing recipe,” Yan said. “Along with rapid bone growth, we also observed nerve regeneration and anti-inflammatory effects at the scaffold site—two factors critical for long-term recovery.”
The scaffold’s design also enables precise nutrient delivery. Instead of relying on oral supplements that may only partially reach the injury site, the implant delivers magnesium and glutamine directly where needed, ensuring a higher concentration at the site of repair.
Additionally, the polymer itself naturally exhibits photoluminescent and photoacoustic properties, allowing it to be imaged after implantation. “With its photoacoustic capability, CitraBoneQMg could potentially be tracked in vivo using ultrasound, even under deep tissue,” Xu noted.
The Penn State team included Xu, Yan, doctoral students Ethan Gerhard, Rohitraj Ray, and Yuqi Wang, along with faculty members Sri-Rajasekhar Kothapalli, associate professor of biomedical engineering, and April D. Armstrong, chair of the Department of Orthopaedics and Rehabilitation and chief of the Shoulder and Elbow Service at Penn State Health.
