Abstract
Multiple growth factors can be administered to mimic the natural process of bone healing in bone tissue engineering. We investigated the effects of sequential release of bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) from polylactide-poly (ethylene glycol)-polylactide (PELA) microcapsule-based scaffolds on bone regeneration. To improve the double emulsion/solvent evaporation technique, VEGF was encapsulated in PELA microcapsules, to which BMP-2 was attached. The scaffold (BMP-2/PELA/VEGF) was then fused to these microcapsules using the dichloromethane vapor method. The bioactivity of the released BMP-2 and VEGF was then quantified in rat mesenchymal stem cells (rMSCs). Immunoblotting analysis showed that BMP-2/PELA/VEG promoted the differentiation of rMSCs into osteoblasts via the MAPK and Wnt pathways. Osteoblast differentiation was assessed through alkaline phosphatase expression. When compared with simple BMP-2 plus VEGF group and pure PELA group, osteoblast differentiation in BMP-2/PELA/VEGF group significantly increased. An MTT assay indicated that BMP-2-loaded PELA scaffolds had no adverse effects on cell activity. BMP-2/PELA/VEG promoted the differentiation of rMSCs into osteoblast via the ERK1/2 and Wnt pathways. Our findings indicate that the sequential release of BMP-2 and VEGF from PELA microcapsule-based scaffolds is a promising approach for the treatment of bone defects.
Highlights
Bone tissue engineering aims to generate functional bone tissue for the replacement of defective bone, re-establishing normal function in humans [1]
We investigated the effects of bone morphogenetic protein-2 (BMP-2)- and vascular endothelial growth factor (VEGF)-based microcapsules on the growth of rat mesenchymal stem cells (rMSCs)
The concentrations of Bone morphogenetic proteins (BMPs)-2 and VEGF released from BMP-2/PELA/VEGF scaffolds were measured by ELISA (Figure 1C)
Summary
Bone tissue engineering aims to generate functional bone tissue for the replacement of defective bone, re-establishing normal function in humans [1]. Mesenchymal stem cells (MSCs), which can differentiate in vitro into various mesenchymal lineages, are widely used for this purpose because they can be isolated from different sources [2,3]. Bone marrow-derived mesenchymal stem cells (bMSCs) are multipotent adult stem cells, whose osteogenic differentiation potential has been reported in several in vitro studies, have become an important source of cells for engineered tissue repair and cell therapy [4]. It has been reported that the degree of microcapsule expression is dependent on the composition of the growth medium, the stage of growth, and whether the organisms are cultured on solid or liquid medium [6,7]. Growth medium with added VEGF has been found to enhance microcapsule expression, which is attributed to the low-phosphate nature of this medium [8,9]
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