Hydroxyapatite-Based Scaffold Combined with 2 Polydeoxyribonucleotide (PDRN) Promotes Bone Regeneration in 3 a Rat Calvarial Critical-Size Defect Model

When a bone breaks, the body usually knows exactly how to fix it. It sends cells to the site, builds a temporary bridge, and slowly remodels it into strong, solid bone. But this natural repair system has a limit. If a piece of bone is missing entirely—perhaps due to a severe injury, a tumor removal, or a birth defect—the body cannot bridge the gap on its own. The space remains empty, filled only with soft scar tissue, leaving the structure weak and unstable. For decades, surgeons have tried to solve this by taking healthy bone from another part of the patient's body and grafting it into the hole. While this works, it requires a second surgery, causes pain at the donor site, and often does not provide enough material for large gaps. This has driven scientists to look for synthetic alternatives: materials that can act as a temporary scaffold, guiding the body's own cells to rebuild the missing bone without needing a second surgery.

The challenge lies in finding a material that does more than just fill the space. A good replacement must be porous enough to let blood vessels and cells grow into it, and it must be chemically similar enough to natural bone to encourage the body to accept it. One promising candidate is a ceramic made from hydroxyapatite, the same mineral that gives our bones their hardness. However, ceramic alone can be stiff and slow to integrate with living tissue. To improve this, researchers have begun mixing in biological molecules that act as signals, telling cells to grow faster and repair tissue more effectively. One such molecule is polydeoxyribonucleotide, or PDRN, a substance derived from DNA that has been shown to help heal wounds and stimulate blood flow. The big question was whether combining this biological signal with a specific type of bone scaffold would work better than using either one alone, and if the texture of the scaffold itself mattered.

A team of researchers at Seoul National University Hospital set out to answer this by testing different combinations in a controlled animal model. They created a precise, circular hole in the skull of thirty rats. This hole was large enough that it would never heal on its own, mimicking the difficult "critical-size" defects seen in human patients. The researchers divided the rats into five groups. One group received no treatment, serving as a baseline to show what happens when nothing is done. The other four groups received a synthetic bone graft, but with different ingredients. Two groups received a block of the ceramic material, while the other two received a version of that ceramic mixed with collagen, a protein that makes up the soft framework of our bones. Within each of these pairs, one group received the ceramic alone, and the other received the ceramic soaked in the PDRN solution.

Over the course of eight weeks, the researchers watched how the bone healed. They used high-resolution 3D imaging to measure exactly how much new bone had formed to fill the hole. The results showed a clear difference between the groups. The rats that received no treatment had almost no new bone, with the hole remaining mostly filled with soft tissue. The rats that received the ceramic blocks alone did better, filling about half of the space with new bone. The rats that received the ceramic mixed with PDRN did even better, but the most dramatic improvement came from the group that received the collagen-containing ceramic soaked in PDRN. In this group, the new bone filled nearly three-quarters of the defect, a significantly higher amount than any other group.

The researchers also looked at the quality of the new bone under a microscope. In the group with the best results, the new bone was not just a random jumble of cells; it had organized itself into a mature, layered structure that closely resembles healthy adult bone. This suggests that the combination of the collagen scaffold and the PDRN signal did more than just speed up growth; it helped the bone mature properly. The study found that the collagen in the scaffold likely played a key role. While the ceramic block alone was a decent platform for bone growth, the collagen version seemed to create a better environment for the PDRN to work. It appears that the collagen helped hold the biological signal in place and allowed it to interact more effectively with the cells trying to rebuild the bone.

This research suggests that the success of a bone repair treatment depends not just on the ingredients used, but on how they are put together. Simply adding a healing molecule to a standard scaffold did not produce the best results. Instead, the specific combination of a collagen-based scaffold and the PDRN signal created a synergistic effect, where the whole was greater than the sum of its parts. The findings indicate that for difficult bone defects, using a scaffold that mimics the natural protein structure of bone, combined with a biological signal to stimulate growth, could offer a powerful alternative to taking bone from a patient's own body. While these results were observed in rats and further testing will be needed to confirm how this works in humans, the study provides a clear path forward for designing better materials to help the body heal its most stubborn injuries.