Abstract
The aim of this study was to investigate the feasibility and advantages of the dual delivery of bone morphogenetic protein-2 (BMP-2) and basic fibroblast growth factor (bFGF) from nano-composite scaffolds (PLGA/PCL/nHA) loaded with vascular stents (PLCL/Col/nHA) for large bone defect regeneration in rabbit mandibles. Thirty-six large bone defects were repaired in rabbits using engineering bone composed of allogeneic bone marrow mesenchymal stem cells (BMSCs), bFGF, BMP-2 and scaffolds composed of PLGA/PCL/nHA loaded with PLCL/Col/nHA. The experiments were divided into six groups: BMSCs/bFGF/BMP-2/scaffold, BMSCs/BMP-2/scaffold, BMSCs/bFGF/scaffold, BMSCs/scaffold, scaffold alone and no treatment. Sodium alginate hydrogel was used as the carrier for BMP-2 and bFGF and its features, including gelling, degradation and controlled release properties, was detected by the determination of gelation and degradation time coupled with a controlled release study of bovine serum albumin (BSA). AlamarBlue assay and alkaline phosphatase (ALP) activity were used to evaluate the proliferation and osteogenic differentiation of BMSCs in different groups. X-ray and histological examinations of the samples were performed after 4 and 12 weeks post-implantation to clarify new bone formation in the mandible defects. The results verified that the use of sodium alginate hydrogel as a controlled release carrier has good sustained release ability, and the combined application of bFGF and BMP-2 could significantly promote the proliferation and osteogenic differentiation of BMSCs (p < 0.05 or p < 0.01). In addition, X-ray and histological examinations of the samples exhibited that the dual release group had significantly higher bone formation than the other groups. The above results indicate that the delivery of both growth factors could enhance new bone formation and vascularization compared with delivery of BMP-2 or bFGF alone, and may supply a promising way of repairing large bone defects in bone tissue engineering.
Highlights
Large bone defects of the oral and maxillofacial regions caused by trauma, inflammation, cancer and congenital malformations have been a significant problem in stomatology [1]
Bone tissue engineering has been considered as the most promising solution for repairing bone defects in clinical practice, which may help to optimize an efficient induction of bone formation via the delivery of multiple morphogenetic signaling factors [6,7,8]
The cell proliferation in the bone marrow mesenchymal stem cells (BMSCs)/bone morphogenetic protein-2 (BMP-2)/scaffold and BMSCs/basic fibroblast growth factor (bFGF)/scaffold groups appeared to have similar behavior and were significantly faster than the BMSCs/scaffold group (p < 0.05). These results indicate that both growth factors, BMP-2 and bFGF, could promote the proliferation of BMSCs and the combined application was better than using either alone
Summary
Large bone defects of the oral and maxillofacial regions caused by trauma, inflammation, cancer and congenital malformations have been a significant problem in stomatology [1]. Traditional techniques for repairing bone defects mainly include the implantation of bone autografts, allografts, xenografts and artificial bones [2,3]. Bone tissue engineering has been considered as the most promising solution for repairing bone defects in clinical practice, which may help to optimize an efficient induction of bone formation via the delivery of multiple morphogenetic signaling factors [6,7,8]. During the process of bone regeneration, cell growth factors, such as BMPs, bFGF, and VEGF, regulate cellular behavior and the tissue response. The strong spatial and temporal control under which these growth factors are presented to cells under normal conditions, stresses the relevance of spatiotemporally controlling the therapeutic delivery of multiple factors for bone tissue regeneration
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