title: Dual delivery of BMP-2 and bFGF from a new nano-composite scaffold, loaded with vascular stents for large-size mandibular defect regeneration.
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.
authors.affiliation: Institute of Prosthodontics, School of Stomatology, Tongji University, 399 Yanchang Road, Shanghai 200092, China. sjs@tongji.edu.cn.
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Su
authors.forename: Hongzhen
authors.initials: H
authors.lastname: Xu
authors.forename: Jun
authors.initials: J
authors.lastname: Sun
authors.forename: Xue
authors.initials: X
authors.lastname: Gong
authors.forename: Hang
authors.initials: H
authors.lastname: Zhao
mesh_terms: D000464:Alginates / Q000494:pharmacology; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology; D001807:Blood Vessel Prosthesis; D015519:Bone Density / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D020723:Glucuronic Acid / Q000494:pharmacology; D006603:Hexuronic Acids / Q000494:pharmacology; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology; D020007:Implants, Experimental; D008334:Mandible / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053761:Nanocomposites / Q000737:chemistry*; D011817:Rabbits; D011859:Radiography; D012710:Serum Albumin, Bovine / Q000378:metabolism; D015607:Stents; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D006603:Hexuronic Acids; D016222:Fibroblast Growth Factor 2; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D012710:Serum Albumin, Bovine; D020723:Glucuronic Acid; D000469:Alkaline Phosphatase