New use for old drug: Local delivery of puerarin facilitates critical-size defect repair in rats by promoting angiogenesis and osteogenesis

Journal of Orthopaedic TranslationVolume 36, September 2022, Pages 52-63Journal of Orthopaedic TranslationAbstractObjectives

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.

Methods

Puerarin 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.

Results

PTP 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.

Conclusion

Puerarin-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 Article

The 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.

Keywords

Puerarin

PLGA/TCP

Angiogenesis

Osteogenesis

Drug/device combination implant

AbbreviationsBMP-2

Bone morphogenetic protein 2

BV/TV

The ratio of bone volume

β-TCP

β-calcium phosphate

CPC

Calcium phosphate cement

HIF-1α

Hypoxic induction factor-1 alpha

HPLC

High-performance liquid chromatography

LT-RP

Low-temperature rapid prototyping

MRI

Magnetic resonance imaging

PLGA

Poly (lactic-co-glycolic acid)

RSR

Relative survival rate

SEM

Scanning Electron Microscope

TRAP

Tartrate-resistant acid phosphatase

VEGF

Vascular endothelial growth factor

© 2022 The Authors. Published by Elsevier (Singapore) Pte Ltd on behalf of Chinese Speaking Orthopaedic Society.

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