A new study has developed a mineralized DNA hydrogel that combines immunomodulation and sustained bone regeneration. Researchers used tetrahedral DNA nanostructures and calcium phosphate mineralization to construct a scaffold that promotes macrophage activity conducive to bone healing while supporting the growth of osteoblasts. In animal models, the material accelerated bone repair, improved tissue mineralization, and prolonged structural stability. These findings promise to advance the development of next-generation biomaterials for craniofacial reconstruction, wound healing, and the treatment of various intractable bone healing diseases worldwide.

Bone defects caused by trauma, infection, tumors, or congenital diseases remain a major clinical challenge. Surgeons often rely on bone grafts, but these surgeries present numerous challenges, including limited donor bone volume, immune rejection, infection risks, and the need for repeat surgeries. Therefore, researchers in the field of tissue engineering have been searching for biomaterials that can guide the body's natural bone regeneration and control inflammation during the healing process. While hydrogels can mimic the body's extracellular matrix, many existing materials degrade too rapidly to provide long-term regenerative support.

To address this challenge, a research team led by Professor Lin Yunfeng and Professor Tian Taoran from the State Key Laboratory of Oral Diseases and the National Center for Stomatology, West China Hospital of Stomatology, Sichuan University, conducted a study. The researchers developed a mineralized DNA hydrogel called Cap-gel using tetrahedral framework nucleic acids (tiny, programmable DNA nanostructures that can self-assemble into stable three-dimensional scaffolds). This material achieves immunomodulation and sustained osteogenic activity by controlling calcium phosphate mineralization. Their findings were published online on May 8, 2026, in Volume 14 of the journal *Bone Research*.

Scientists are focusing on two crucial biological processes in bone repair: inflammation control and osteogenic processes (i.e., the formation of new bone tissue). They have designed a gel called Cap-Gel to promote the transformation of macrophages into the "M2" repair phenotype, thereby promoting tissue regeneration. Laboratory experiments have shown that this material can reduce the levels of inflammatory markers, including IL-6 and TNF-α, while increasing the levels of anti-inflammatory and regenerative signals such as IL-10, TGF-β, and BMP2. Furthermore, this hydrogel can reduce oxidative stress on immune cells, thus helping to create a more favorable environment for healing. 

Meanwhile, the mineralized structure of Cap-Gel can store calcium ions for extended periods, which are crucial for bone formation and cell signaling. Researchers found that the hydrogel gradually releases calcium ions over several weeks, activating signaling pathways associated with osteogenic differentiation. Compared to the control group, bone marrow stem cells exposed to Cap-gel exhibited stronger expression of osteogenic proteins, including RUNX2, ALP, osteopontin, and type I collagen. The material also promoted the formation of mineralized nodules, indicating its active osteogenic activity.

To evaluate this material in a living system, the research team implanted Cap-Gel into skull defects in rats. Imaging and tissue analysis showed that this hydrogel accelerated bone repair. In the initial implantation period, the material reduced inflammatory infiltration and increased the number of healing-promoting macrophages. Over time, compared to the untreated control group or non-mineralized hydrogel, the Cap-Gel-treated defect sites formed a denser collagen network, a more ordered bone structure, and a larger bone volume. After eight weeks, the regenerated bone exhibited a mature structure and stronger mineralization.

Researchers believe this study has the potential to foster collaboration in regenerative medicine, biomaterials science, nanotechnology, and immunology. Because the material combines programmable DNA nanostructures with bioactive mineral components, it may inspire future strategies in areas such as cartilage repair, tooth reconstruction, chronic wound healing, and implant integration. The ability to modulate immune responses while supporting tissue regeneration is increasingly seen as crucial for successful biomedical engineering.

Professor Tian explained that the project was motivated by the challenges in the field of craniofacial repair. He noted, "Patients with severe bone defects often require multiple surgeries and a long recovery period. We hope to reduce complications and improve long-term healing outcomes by designing materials that can work synergistically with the human immune system."

In summary, these findings demonstrate how programmable DNA nanotechnology can be combined with mineral engineering to create a new generation of regenerative biomaterials. By combining immune modulation with sustained osteogenic processes, Cap-Gel provides a promising framework for therapies that repair complex bone defects and harness the body's own healing potential.

source:

Sichuan University