Author(s)

Yanru Zhang, Kaka AA Katiella, and Hui Zhang

Corresponding Author

Yanru Zhang

Abstract

Purpose: This study was designed to incorporate BMP-4 into poly(lactic-co-glycolic acid) (PLGA) implants and evaluate the local release of BMP-4 biological effects. Method: Using rabbit models of a full thickness knee articular cartilage defect filler after surgical core-decompression. Rabbit BMSCs were isolated, cultured and identified by immunohistochemistry. The plasmid pcDNA3.1-BMP-4 was successfully introduced into BMSCs by electroporation. A double layer PLGA scaffold with a 4 mm diameter was set and implanted in the knee. Forty New Zealand white rabbits were randomly divided equally into four groups: the blank group, PLGA group, BMSCs/PLGA group, and PLGA/BMP-4/BMSCs group. Postoperation follow-up were recorded. HE staining of knee joint was performed at the eighth and sixteenth week. Implanted PLGA was observed under scanning electron microscope. The expression levels of chondrogenic markers SOX-9, collagen II and aggreccan were measured by RT-PCR in experimental groups. Result: The results showed there was no record of inflammatory reaction in the knee joint activity postoperatively. HE staining showed that the wound site in PLGA/BMP-4/BMSCs group improved better than the other 3 groups. RT-PCR results showed that the expression levels of SOX-9, collagen II and aggreccan in the PLGA/BMP-4/BMSCs group were significantly higher (P<0.01) than that in other groups. Conclusion: This study is one of the first to demonstrate the beneficial effect of BMP-4 delivery system integrated in double PLGA implants, suggesting its great potential in postoperative treatment targeting local bone healing and tissue regeneration.

Keywords

Bone morphogenetic protein-4, Bone marrow mesenchymal stem cells, Poly (lactic-co-glycolic acid) PLGA, Biocompatibility, Knee repair, Rabbit models