Bioengineers at Penn State have discovered that ‘citrate’, a chemical based biomaterial on natural product of the bones and citrus fruit can provide extra energy essential for stem cells to construct new bone tissue.
According to the researchers, new understanding of the mechanism that enables citrate to promote bone regeneration could help scientists around the world to develop biodegradable, citrate-releasing scaffolds to act as a template for bone development that accelerates healing in the body.
The research team have been working with citrate for more than 10 years, Jian Yang said, who is a professor of biomedical engineering at Penn State. It is a known fact that 90% of organic citrate in the human body is found in the skeletal tissue, but there are no research studies that suggest the use of citrate as an important component to make biomaterial for bones, he added.
In the new study, researchers tried to understand the role of citrate in bone healing and use that understanding in the development of new biomimetic materials for better bone repair. Findings of the study were detailed in a paper and published in the latest issue of the journal Proceedings of the National Academy of Sciences. Although autografting has been widely used for bone regeneration in the hospital setting, it is not always suitable, such as in case of large wounds or bone tissue removal during cancer treatment.
Synthetic biomaterials are gaining momentum as a replacement and many labs are working on developing them. However, the existing synthetic materials are often associated with inflammation, causing slow bone healing as well as poor healing quality. Further, the body tends to encapsulate the implant with fibrotic tissues preventing its integration with the surrounding bone. In Yang’s material, however, the researchers did not see the encapsulation and chronic inflammation had least significance.
Lead author Chuying Ma, also a doctoral student in Yang’s lab, was asked to identify the little-known mechanism underlying the use of citrate in the body to regenerate bone. She discovered that the stem cell membrane has a transporter, allowing citrate to make way into the cell to increase cellular energy level. To make new bone cells, the stem cells require more amount of energy to support active bone formation. Additionally, dosage and timing of supplying citrate to stem cells are critical. Yang and Ma together coined the newly discovered citrate effect as ‘metabonegenic regulation’.
The researchers also detected a second factor involved in energy production, phosphoserine, an amino acid. With their understanding of the bone regrowth mechanism, the team developed a new biomaterial using both citrate and phosphoserine, and experimented it on rat models.
Early deposition of new bone was seen at one month which is way earlier than the biomaterials incorporated in FDA-approved medical devices, according to the researchers. In the study, two models were tested including cranial bone and femoral condyle bone defects.
Ma revealed that in both the models, the new biomaterial appear to be better than the currently available materials in stimulating early bone formation as well as promoting bone maturation.