Large bone defect repair is a challenging clinical problem due to limited self-repair ability. A well-designed bone filling product should possess the ability to induce tissue in-growth and facilitate neovascularization and new bone formation. Puerarin has been used in clinics for a long time, and recently it was found to be able to promote osteogenesis. This study aimed to investigate a puerarin-based drug/delivery combination implant for promoting large bone defect repair.
MethodsPuerarin was incorporated into the poly (lactic-co-glycolic acid)/β-calcium phosphate (PLGA/TCP, PT) to form a porous PLGA/TCP/Puerarin (PTP) composite scaffold by low-temperature rapid prototyping technology. Its structural and degradation were analyzed in vitro. Then we employed a rat calvarial critical size defect model to assess the potency of the PTP scaffold. MC3T3-E1 cells and EA. hy 926 cells were used to investigate the underlying mechanism.
ResultsPTP scaffold inherited all advantages of PT scaffold in structural, mechanical, and biodegradation, meanwhile puerarin stably and continuously released from PTP scaffold and lasted for 5 months in vitro. At 8 weeks after implantation, the PTP scaffold triggered new bone formation in the macro-pores of the scaffold and inside the scaffold accompanied by the degrading materials. The underlying mechanism revealed that the PTP scaffold induced vascular infiltration and recruit repair cells through stimulating vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2) expressions to promote angiogenesis and osteogenesis.
ConclusionPuerarin-enriched porous PTP scaffold was a promising local delivery system with sustained release of puerarin for facilitating defect repair through getting synergistic angiogenic and osteogenic effects.
The Translational Potential of this ArticleThe PTP scaffold presents a potential drug/device combination medical implant for large bone defect repair, which also provides a new and innovative application for the “old drug” puerarin.
KeywordsPuerarin
PLGA/TCP
Angiogenesis
Osteogenesis
Drug/device combination implant
AbbreviationsBMP-2Bone morphogenetic protein 2
BV/TVThe ratio of bone volume
β-TCPβ-calcium phosphate
CPCCalcium phosphate cement
HIF-1αHypoxic induction factor-1 alpha
HPLCHigh-performance liquid chromatography
LT-RPLow-temperature rapid prototyping
MRIMagnetic resonance imaging
PLGAPoly (lactic-co-glycolic acid)
RSRRelative survival rate
SEMScanning Electron Microscope
TRAPTartrate-resistant acid phosphatase
VEGFVascular endothelial growth factor
© 2022 The Authors. Published by Elsevier (Singapore) Pte Ltd on behalf of Chinese Speaking Orthopaedic Society.
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