Sequentially Regulated Immuno-Osteogenic Bioceramics Enhance the Regeneration of Osteoporotic Bone Defects

Abstract

Sequentially Regulating immune-osteogenesis to orderly transition from the inflammatory phase to bone reconstruction, enhancing bone regeneration while inhibiting osteoclastic resorption, are crucial for treating osteoporotic bone defect. Herein, the sequential loading and controlled release of interleukin-4 (IL-4) and alendronate (AL) based on the 3D-printed β-tricalcium phosphate (β-TCP) scaffolds were achieved via Michael addition reaction combined with physical adsorption. IL-4 was rapidly released within two days, promoting M2 polarization of macrophage   and secretion of anti-inflammatory and bone-associated factors. AL was sequentially released over a two-week period, promoting the osteogenic differentiation of mBMSCs while inhibiting osteoclast formation. Bone regeneration efficacy in vivo was assessed utilizing an osteoporotic rat femoral defect model. Micro-CT and histological analyses revealed that the functionalized scaffolds (TCP-PDA/AL-IL-4) exhibited superior bone-enhancing properties. Significantly, the bone mineral apposition rate (MAR) and the newly formed bone increased in the TCP-PDA/AL-IL-4 groups, while the osteoclast population reduced. This study proposes a highly effective strategy for developing bone regeneration and repair materials specifically tailored for the osteoporotic bone defect.

Note:
Funding declaration: This work was supported by the National Key R&D Program of China (2021YFB3800800), the National Natural Science Foundation of China (52172281, 32201089 ), the Guangzhou Key R&D Program (202206040001), the Science and Technology Program of Guangzhou City (Grant No. 2024A04J6187).

Conflict of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influenced the work reported in this paper.

Ethical Approval: The implantation experiments and protocols were approved by the Ethics Committee of the Animal Center, South China University of Technology.

Keywords: Sequential regulation, Immune-osteogenesis, Osteoporotic bone defect, bone regeneration