Researchers at Sichuan University have developed a mineralised DNA hydrogel, called Cap-gel, that has shown the ability to reduce inflammation and promote bone regeneration in preclinical models.
Bone defects occuring from trauma, infection, tumours and congenital disorders are a big problem for clinicians. While bone grafts are widely used, they can be limited by donor shortages, immune rejection, infection risks and the need for additional surgery. Researchers have therefore sought biomaterials capable of supporting natural bone regeneration while also controlling inflammation during the healing process.
Now, a newly developed mineralised DNA hydrogel could offer a new approach to treating difficult bone defects by combining immune regulation with sustained bone regeneration, according to a new study.
The material, known as Cap-gel, was designed by researchers at Sichuan University in China to address longstanding challenges in bone tissue engineering. In preclinical studies, the hydrogel accelerated bone repair, improved tissue mineralisation and maintained structural stability for longer than conventional hydrogel approaches.
Combining immune regulation and bone regeneration
The study was led by Professor Yunfeng Lin and Professor Taoran Tian from the State Key Laboratory of Oral Diseases and National Center for Stomatology at West China Hospital of Stomatology, Sichuan University.
The team developed Cap-gel using tetrahedral framework nucleic acids, programmable DNA nanostructures that self-assemble into stable three-dimensional scaffolds. The hydrogel was further enhanced through calcium phosphate mineralisation, allowing it to support both immune regulation and long-term bone formation.
Researchers focused on two key biological processes involved in bone repair: inflammation control and osteogenesis. Laboratory experiments showed that Cap-gel encouraged macrophages to adopt the M2 phenotype, which is associated with tissue regeneration and healing.
The team developed Cap-gel using tetrahedral framework nucleic acids, programmable DNA nanostructures that self-assemble into stable three-dimensional scaffolds
The material reduced levels of inflammatory markers including IL-6 and TNF-α while increasing regenerative signalling molecules such as IL-10, TGF-β and BMP2. It also reduced oxidative stress in immune cells, creating conditions that were more favourable for tissue repair.
“Our goal was to create a biomaterial that does more than simply fill a defect,” explained Professor Lin. “We wanted a scaffold that could actively communicate with immune cells and stem cells so the healing environment becomes regenerative from the very beginning.”
Sustained calcium release supports healing
In addition to its immune-modulating properties, Cap-gel acted as a reservoir for calcium ions, which play a critical role in bone formation and cellular signalling.
The researchers found that calcium was released gradually over several weeks, activating pathways associated with osteogenic differentiation. Bone marrow stem cells exposed to the material showed increased expression of proteins linked to bone formation, including RUNX2, ALP, osteopontin and collagen I.
The hydrogel also promoted the formation of mineralised nodules, indicating active bone-building activity.
Improved repair in animal models
To test its performance in living systems, the researchers implanted Cap-gel into skull bone defects in rats.
Imaging and tissue analysis revealed accelerated healing compared with untreated defects and non-mineralised hydrogels. Early after implantation, the material reduced inflammatory cell infiltration and increased the presence of pro-healing macrophages. Over eight weeks, treated defects developed denser collagen networks, more organised bone structures and greater bone volume.
Imaging and tissue analysis revealed accelerated healing compared with untreated defects and non-mineralised hydrogels
According to the researchers, the findings could have implications beyond bone repair, potentially informing future approaches to cartilage regeneration, dental reconstruction, chronic wound healing and implant integration.
“Patients with severe bone defects often require multiple surgeries and prolonged recovery,” said Professor Tian. “By designing materials that work together with the body’s immune system, we hope to reduce complications and improve long-term healing outcomes.”
Promising signs
The researchers believe the work demonstrates how programmable DNA nanotechnology and mineral engineering can be combined to create a new generation of regenerative biomaterials capable of supporting both immune regulation and long-term tissue regeneration.
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