The supporting structure of a bone implant (left), with an enlarged image of the bone cells seeded on it (right). (Photo credit: Adapted from G. Kerckhofs et al, Acta Biomaterialia, (2016) )
Preconditioning bone cells to withstand a lack of oxygen and nutrients at the fracture site before implantation may help improve their survival.
A media release from KU Leuven explains that, with large bone fractures or defects, one’s body may not be able to repair it adequately on its own. Therefore, to support bone regeneration, researchers are developing living implants, which consist of cells seeded on supporting structures made of biological material.
Professor Geert Carmeliet of the Clinical and Experimental Endocrinology Unit notes in the release that usually, only 30% of the implanted bone cells survive the first few days because the blood vessels around the fracture, which deliver oxygen and nutrients to the cells, are also damaged.
“The ingrowth of new blood vessels into the implant takes time, and until then, the cells are out of fuel since oxygen and nutrient supply is insufficient. At the same time, the starved bone cells produce harmful oxygen radicals and thereby disturb the natural balance between antioxidants and oxygen radicals. An excess of these oxygen radicals causes irreversible cell damage,” Carmeliet says in the release.
Doctoral student Steve Stegen tested in mice how he could better equip the bone cells for the time between implantation and ingrowth of the blood vessels. By inactivating the oxygen sensor PHD2 before implantation, Stegen switched on a survival mode in bone cells, per the release.
“As a result, bone cells activate a dual defense mechanism. First, bone cells increase storage of an emergency fuel in the form of glycogen, which is in fact a sugar reservoir. In addition, bone cells start using glutamine—an amino acid—to produce more antioxidants to neutralize the increased production of harmful oxygen radicals. These two adjustments allow bone cells to be self-supporting in terms of energy generation and to protect themselves against an increased level of oxygen radicals,” as explained in the release.
Carmeliet adds that the oxygen sensor PHD2 can be inactivated via genetic engineering, but also by administering therapeutic molecules. “Reprogramming bone cells obtained from patients might increase their survival rate from 30% to 60%, which will ultimately lead to better bone regeneration. In future research, we will examine whether this technique also works in even larger bone defects and by using human cells,” he says.
The study was published recently in Cell Metabolism.
[Source(s): KU Leuven, Science Daily]
