Nacre-derived biphasic calcium phosphate composite scaffolds with dual osteogenic/angiogenic potential for efficient bone defect repair

Researchers from Ocean University of China and Qilu Hospital of Shandong University have developed nacre-derived biphasic calcium phosphate (BCP) composite scaffolds that combine osteogenic and angiogenic functions. The study demonstrates that these biomimetic “smart scaffolds” not only accelerate bone regeneration but also promote blood vessel formation, showing great promise for efficient bone defect repair.

Bone defects caused by trauma, disease, or surgery remain a significant challenge in clinical practice. Current treatment options, including autologous bone grafts and allogeneic transplants, often lead to complications such as donor site morbidity, immune rejection, and limited availability. These shortcomings have driven an urgent demand for artificial bone substitutes that can provide both structural support and biological functionality.

To address this challenge, a team led by Dr. Yan Yang from Ocean University of China and Dr. Chao Zhou from Qilu Hospital of Shandong University has developed a novel nacre-derived biphasic calcium phosphate (BCP) composite scaffold reinforced with sodium alginate (SA). By mimicking the unique organic–inorganic structure of natural nacre, the researchers designed a “smart scaffold” with tunable ratios of hydroxyapatite (HAP) and β-tricalcium phosphate (β-TCP), aiming to balance mechanical strength, controlled degradation, and dual bioactivity.

“This nacre-inspired design provides an elegant solution for bone tissue engineering,” says Dr. Yan Yang. “By carefully adjusting the composition, we created scaffolds that not only support new bone formation but also promote vascular growth, two essential processes for successful bone repair.”

In laboratory studies, the optimized scaffold (SH5, with a 1:1 HAP/β-TCP ratio) demonstrated remarkable performance. It enhanced osteoblast adhesion, proliferation, and differentiation, as evidenced by increased expression of key osteogenic genes such as RUNX2, COL-1, ALP, and OPN. At the same time, the scaffold promoted endothelial cell migration and tube formation, highlighting its angiogenic capacity. These dual activities distinguish the scaffold from traditional bone substitutes, which often lack vascularization potential.

Animal experiments further validated these findings. In a rat cranial defect model, the SH5 scaffold significantly improved bone regeneration, collagen deposition, and mineralization, while achieving seamless integration with host tissue. Importantly, histological analysis confirmed strong expression of osteogenic proteins including osteocalcin (OCN), osteopontin (OPN), and osteoprotegerin (OPG), demonstrating the scaffold’s ability to stimulate both early and mature stages of bone formation.

According to Dr. Chao Zhou, “The dual osteogenic and angiogenic effects we observed suggest that this material could serve as bone graft substitute, overcoming the limitations of current treatments. It is particularly promising for bone defects fillers that require rapid healing and vascularization.”

The researchers emphasize that the nacre-derived BCP/SA scaffold represents a versatile platform with wide potential in bone tissue engineering. Looking ahead, they plan to further optimize scaffold degradation rates to synchronize with natural bone healing, paving the way for future clinical applications.

This paper was published in Biofunctional Materials (ISSN: 2959-0582), an online multidisciplinary open access journal aiming to provide a peer-reviewed forum for innovation, research and development related to bioactive materials, biomedical materials, bio-inspired materials, bio-fabrications and other bio-functional materials.

Citation: Dong W, Zhang L, Wang K, Zhang Y, Li Y, et al. Biofunct. Mater. 2025(3):0013. https://doi.org/10.55092/bm20250013