Journal
JOURNAL OF ORTHOPAEDIC TRANSLATION
Volume 31, Issue -, Pages 41-51Publisher
ELSEVIER
DOI: 10.1016/j.jot.2021.10.002
Keywords
Biomaterials; Cucurbitacin B; Angiogenesis; Bone regeneration; 3D printing
Categories
Funding
- National Key R&D Program of China [2018YFC1705205]
- Foreign cooperation project of Chinese Academy of Sciences [GJHZ2063]
- National Natural Science Foundation of China [81773964, 82104497, 92068117, 81871809]
- Guangdong Youth Talent Support Program of Science and Technological Innovation [2017TQ04X885]
- Guangdong Basic and Applied Basic Research Fund [2020B1515120052]
- Shenzhen International Collaborative Project [GJHZ20190821160803823]
- Science and Technology Innovation Fund of Shenzhen [JCYJ20180302150101316, JCYJ20170818153602439]
- Sanming Project of Medicine in Shenzhen [SZSM201808072]
- Development and Reform Commission of Shenzhen Municipality [XMHT20190106001]
- Shenzhen Double Chain Project for Innovation and Development Industry - Bureau of Industry and Infor-mation Technology of Shenzhen [201908141541]
- Discipline construction project of Guangdong Medical University [4SG21002G]
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The study demonstrates that CuB can enhance angiogenesis in vitro and promote neovascularization and bone regeneration in a rat model. CuB-incorporated scaffold showed improved mechanical properties and successfully stimulated angiogenic signaling pathways, highlighting its potential as a therapeutic agent in tissue engineering for bone repair.
Objectives: Vascularization is an essential step in successful bone tissue engineering. The induction of angiogenesis in bone tissue engineering can be enhanced through the delivery of therapeutic agents that stimulate vessel and bone formation. In this study, we show that cucurbitacin B (CuB), a tetracyclic terpene derived from Cucurbitaceae family plants, facilitates the induction of angiogenesis in vitro. Methods: We incorporated CuB into a biodegradable poly (lactide-co-glycolide) (PLGA) and beta-tricalcium phosphate (beta-TCP) biomaterial scaffold (PT/CuB) Using 3D low-temperature rapid prototyping (LT-RP) technology. A rat skull defect model was used to verify whether the drug-incorporated scaffold has the effects of angiogenesis and osteogenesis in vivo for the regeneration of bone defect. Cytotoxicity assay was performed to determine the safe dose range of the CuB. Tube formation assay and western blot assay were used to analyze the angiogenesis effect of CuB. Results: PT/CuB scaffold possessed well-designed bio-mimic structure and improved mechanical properties. CuB was linear release from the composite scaffold without affecting pH value. The results demonstrated that the PT/CuB scaffold significantly enhanced neovascularization and bone regeneration in a rat critical size calvarial defect model compared to the scaffold implants without CuB. Furthermore, CuB stimulated angiogenic signaling via upregulating VEGFR2 and VEGFR-related signaling pathways. Conclusion: CuB can serve as promising candidate compound for promoting neovascularization and osteogenesis, especially in tissue engineering for repair of bone defects. The translational potential of this article: This study highlights the potential use of CuB as a therapeutic agent and strongly support its adoption as a component of composite scaffolds for tissue-engineering of bone repair.
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