title: Adipose-derived stem cells and BMP-2 delivery in chitosan-based 3D constructs to enhance bone regeneration in a rat mandibular defect model.
abstract: Reconstructing segmental mandiblular defects remains a challenge in the clinic. Tissue engineering strategies provide an alternative option to resolve this problem. The objective of the present study was to determine the effects of adipose-derived stem cells (ASCs) and bone morphogenetic proteins-2 (BMP-2) in three-dimensional (3D) scaffolds on mandibular repair in a small animal model. Noggin expression levels in ASCs were downregulated by a lentiviral short hairpin RNA strategy to enhance ASC osteogenesis (ASCs(Nog-)). Chitosan (CH) and chondroitin sulfate (CS), natural polysaccharides, were fabricated into 3D porous scaffolds, which were further modified with apatite coatings for enhanced cellular responses and efficient delivery of BMP-2. The efficacy of 3D apatite-coated CH/CS scaffolds supplemented with ASCs(Nog-) and BMP-2 were evaluated in a rat critical-sized mandibular defect model. After 8 weeks postimplantation, the scaffolds treated with ASCs(Nog-) and BMP-2 significantly promoted rat mandibular regeneration as demonstrated by micro-computerized tomography, histology, and immunohistochemistry, compared with the groups treated with ASCs(Nog-) or BMP-2 alone. These results suggest that our combinatorial strategy of ASCs(Nog-)+BMP-2 in 3D apatite microenvironments can significantly promote mandibular regeneration, and these may provide a potential tissue engineering approach to repair large bony defects.
authors: 1 Division of Advanced Prosthodontics, UCLA School of Dentistry , Los Angeles, California.
authors: Jiabing
authors: J
authors: Fan
authors: Hyejin
authors: H
authors: Park
authors: Matthew K
authors: MK
authors: Lee
authors: Olga
authors: O
authors: Bezouglaia
authors: Armita
authors: A
authors: Fartash
authors: Jinku
authors: J
authors: Kim
authors: Tara
authors: T
authors: Aghaloo
authors: Min
authors: M
authors: Lee
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D002352:Carrier Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D008334:Mandible / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology*; D008810:Mice, Inbred C57BL; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D011923:Rats, Nude; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D054457:Tissue Scaffolds / Q000737:chemistry*; D055114:X-Ray Microtomography; D000099176:Noggin Protein
chemical_list: D055396:Bone Morphogenetic Protein 2; D002352:Carrier Proteins; D048271:Chitosan; D003094:Collagen; D015675:Osteocalcin; D000099176:Noggin Protein; C480355:chitosan sulfate