SONFH is one of the leading causes of non-traumatic osteonecrosis. Reported in up to 9%–40% of patients receiving prolonged or high-dose glucocorticoid therapy, the condition progressively weakens the femoral head and can eventually lead to joint collapse, making effective bone repair a major clinical challenge. Although core decompression is the standard treatment for early-stage disease, it cannot fully restore bone repair because persistent inflammation prevents the damaged tissue from healing.
To address this challenge, a research team led by Dr. Yan Xiong from the Department of Orthopaedics, Army Medical University (Third Military Medical University), China, Dr. Meng Tian from the Department of Neurosurgery and Neurosurgery Research Laboratory, Sichuan University, China, and Dr. Pengde Kang from the Department of Orthopedic, Sichuan University, China, reports a promising strategy focused on a coral-inspired, 3D-printed immunoreprogramming scaffold. They developed a scaffold made of multi-walled carbon nanotubes (MWCNT) and nano-hydroxyapatite (nHA) to enhance bone repair by reprogramming immune cells. The study was published in Volume 14 of the journal Bone Research on June 30, 2026.
"Current treatments mainly provide structural support but do not address the pathological immune microenvironment that prevents bone regeneration. Our coral-inspired immunoreprogramming strategy provides a new approach for targeting this microenvironment and promoting bone repair," says Dr. Xiong.
One of the major obstacles to healing in SONFH is an "immune freeze"—a persistent inflammatory state in which macrophages, immune cells that normally coordinate tissue repair, remain locked in a pro-inflammatory (M1) state instead of transitioning to the tissue-repairing M2 state. As a result, inflammation persists, new blood vessel formation is impaired, and damaged bone struggles to regenerate even after surgical intervention. Inspired by the hierarchical pore structure of coral, the team developed a 3D-printed scaffold that combines the immune-regulating properties of MWCNT with the bone-like mineral characteristics of nHA. While the MWCNT component was designed to encourage macrophages to switch to the reparative M2 state, the nHA component provides a biomimetic mineral matrix that supports the attachment, growth, and differentiation of bone-forming cells. The researchers evaluated the scaffold using both in vitro cell-based experiments and in vivo rabbit models of SONFH.
Their findings showed that the scaffold successfully shifted macrophages from the inflammatory M1 state to the reparative M2 state, reducing inflammatory responses while creating a more favorable environment for healing. This immune reprogramming promoted the migration and osteogenic differentiation of bone marrow mesenchymal stem cells and enhanced angiogenesis, the formation of new blood vessels that supply oxygen and nutrients to regenerating tissue. Compared with conventional scaffolds, the coral-inspired scaffold also improved new bone formation and reconstruction of bone defects in the animal model.
Further analyses revealed that these effects were associated with activation of the PI3K-AKT signaling pathway, which regulates several cellular processes involved in tissue repair. By combining immune regulation with structural support, the scaffold addressed one of the key biological barriers that limit bone regeneration in SONFH, suggesting that modifying the local immune microenvironment may be just as important as repairing the bone itself.
"The coral-inspired immunoreprogramming technique proposed in this study provides a new strategy for targeting the regulation of the pathological microenvironment in SONFH. Although further studies are needed before clinical application, our findings provide a foundation for developing regenerative therapies that improve bone repair by restoring a pro-regenerative immune environment," concludes Dr. Tian.
