title: Reconstructing jaw defects with MSCs and PLGA-encapsulated growth factors.
abstract: Cell and growth factor-based tissue engineering has shown great potentials for skeletal regeneration. This study tested its feasibility in reconstructing large mandibular defects and compared the efficacy of varied construction materials and sealing methods. Bilateral mandibular critical-size (5-cm(3)) defects were created on six 4-month-old domestic pigs, and grafted with β-tricalcium phosphate (βTCP) only (Group-A), βTCP with autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) (Group-B), and βTCP with BM-MSCs and biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres containing bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) (Group-C). The buccal sides of Groups-B/-C were either sealed by fibrin sealant or by a biodegradable PLGA barrier membrane before soft-tissue closure. Computed tomography (CT), microCT and histology analyses were performed 12 weeks postoperatively. In vitro data demonstrated that BM-MSCs, with MSC properties confirmed, remained vital after integration with βTCP; and PLGA microspheres exhibited an initial burst followed by slow and continuous release of growth factors over a period of 28 days. In vivo data demonstrated that Group-B/-C sites had significantly greater gap obliteration, higher tissue mineral densities and more residual βTCP granules (p<0.05, Kruskal-Wallis tests). Qualitatively, Group-B/-C defect sites had started remodeling while Group-A sites were mainly forming new bone to bridge the gaps. Furthermore, βTCP degradation was not mediated by macrophages or osteoclasts, and was significantly slowed down by sealing the defects with barrier membrane. Combined, these data present a promising formulation composed of βTCP granules, autologous MSCs, controlled-release growth factors and biodegradable PLGA barrier membrane for the reconstruction of critical-size mandibular defects.
authors.affiliation: Division of Biosciences, College of Dentistry, The Ohio State University Columbus, Ohio, USA.
authors.forename: Boon Ching
authors.initials: BC
authors.lastname: Tee
authors.affiliation: Department of Pharmaceutical Sciences and Biomedical Engineering, The Biointerfaces Institute, University of MichiganAnn Arbor, Michigan, USA; Current Address: GlaxoSmithKlineKing of Prussia, PA 19406, USA.
authors.forename: Kashappa Goud H
authors.initials: KG
authors.lastname: Desai
authors.affiliation: Division of Oral and Maxillofacial Surgery, College of Dentistry, The Ohio State University Columbus, Ohio, USA.
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Kennedy
authors.affiliation: Division of Oral and Maxillofacial Surgery, College of Dentistry, The Ohio State University Columbus, Ohio, USA.
authors.forename: Brittany
authors.initials: B
authors.lastname: Sonnichsen
authors.affiliation: Division of Orthodontics, College of Dentistry, The Ohio State University Columbus, Ohio, USA.
authors.forename: Do-Gyoon
authors.initials: DG
authors.lastname: Kim
authors.affiliation: Division of Orthodontics, College of Dentistry, The Ohio State University Columbus, Ohio, USA.
authors.forename: Henry W
authors.initials: HW
authors.lastname: Fields
authors.affiliation: Division of Oral Pathology & Radiology, College of Dentistry, The Ohio State University Columbus, Ohio, USA.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Mallery
authors.affiliation: Department of Pharmaceutical Sciences and Biomedical Engineering, The Biointerfaces Institute, University of Michigan Ann Arbor, Michigan, USA.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Schwendeman
authors.affiliation: Division of Orthodontics, College of Dentistry, The Ohio State University Columbus, Ohio, USA.
authors.forename: Zongyang
authors.initials: Z
authors.lastname: Sun
keywords: Bone tissue engineering; biodegradable barrier membrane; bone marrow-derived mesenchymal stem cells; controlled-release growth factors; critical-size mandibular defect