An anti-infection and biodegradable TFRD-loaded porous scaffold promotes bone regeneration in segmental bone defects: experimental studies

抗感染、可生物降解的 TFRD 负载多孔支架促进节段性骨缺损中的骨再生:实验研究

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作者:Haixiong Lin, Zige Li, Zhenze Xie, Shengyao Tang, Minling Huang, Junjie Feng, Yuhan Wei, Zhen Shen, Ruoyu Zhou, Yuanlan Feng, Huamei Chen, Yueyi Ren, Feng Huang, Xiaotong Wang, Ziwei Jiang

Background

Addressing segmental bone defects remains a complex task in orthopedics, and recent advancements have led to the development of novel drugs to enhance the bone regeneration. However, long-term oral administration can lead to malnutrition and poor patient compliance. Scaffolds loaded with medication are extensively employed to facilitate the restoration of bone defects.

Conclusion

Porous scaffolds loaded with TFRD can reduce infection, be biodegradable, and induce angiogenesis, presenting a novel approach for addressing tibial segmental bone defects.

Methods

Inspired by the local application of total flavonoids of Rhizoma Drynariae (TFRD) in the treatment of fracture, a novel 3D-printed HA/CMCS/PDA/TFRD scaffold with anti-infection, biodegradable and induced angiogenesis was designed, and to explore its preclinical value in segmental bone defect of tibia.

Results

The scaffold exhibited good degradation and drug release performance. In vitro, the scaffold extract promoted osteogenesis by enhancing bone-related gene/protein expression and mineral deposition in BMSCs. It also stimulated endothelial cell migration and promoted angiogenesis through the upregulation of specific genes and proteins associated with cell migration and tube formation. This may be attributed to the activation of the PI3k/AKT/HIF-1α pathway, facilitating the processes of osteogenesis and angiogenesis. Furthermore, the HA/CMCS/PDA/TFRD scaffold was demonstrated to alleviate infection, enhance angiogenesis, promote bone regeneration, and increase the maximum failure force of new formed bone in a rat model of segmental bone defects.

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