title: Heterobifunctional poly(ethylene glycol)-tethered bone morphogenetic protein-2-stimulated bone marrow mesenchymal stromal cell differentiation and osteogenesis.
abstract: We describe a biomimetic mode of insoluble signaling stimulation to provide target delivery of bone morphogenetic protein-2 (BMP-2), with the aim of prolonging the retention of BMP-2 use in bone tissue engineering and to enable its localized release in response to cellular activity. In our novel localization process, we used heterobifunctional acrylate-N-hydroxysuccinimide poly(ethylene glycol) (PEG) as a spacer to tether BMP-2 onto a poly(lactide-co-glycolide) scaffold. Use of PEG-tethered BMP-2 was feasible because BMP-2 retained its activity after covalent conjugation. The PEG-tethered BMP-2 conjugate sustained stimulation and retained its mitogenic activity, notably affecting pluripotent stem cell proliferation and differentiation. We seeded the scaffolds with bone marrow-derived mesenchymal stromal cells as progenitor cells to evaluate their morphology and phenotypic expression. We also created bilateral, full-thickness cranial defects in rabbits to investigate the osteogenic effect of cultured mesenchymal stromal cells on bone regeneration in vivo. Histomorphometry and histology demonstrated that the PEG-tethered BMP-2 conjugate enhanced de novo bone formation after surgery. Our work revealed the potential for biomimetic surface engineering by entrapping signaling growth factor to stimulate osteogenesis. Our technique may provide a new platform for bone-engineered stem cell therapies.
authors.affiliation: Department of Chemical Engineering, National Tsing Hua University, Hsinchu, and Department of Orthopedic Surgery, College of Medicine, Chang Gung Memorial Hospital-Keelung, Chang Gung University, Keelung, Taiwan.
authors.forename: Hsia-Wei
authors.initials: HW
authors.lastname: Liu
authors.forename: Chih-Hwa
authors.initials: CH
authors.lastname: Chen
authors.forename: Ching-Lin
authors.initials: CL
authors.lastname: Tsai
authors.forename: I-Hsuan
authors.initials: IH
authors.lastname: Lin
authors.forename: Ging-Ho
authors.initials: GH
authors.lastname: Hsiue
mesh_terms: D000818:Animals; D001705:Bioprosthesis; D001854:Bone Marrow Cells / Q000378:metabolism / Q000648:ultrastructure*; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002478:Cells, Cultured; D016503:Drug Delivery Systems; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000648:ultrastructure*; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008938:Mitosis; D010012:Osteogenesis; D039904:Pluripotent Stem Cells / Q000378:metabolism / Q000648:ultrastructure*; D011092:Polyethylene Glycols; D011098:Polyglactin 910; D011817:Rabbits; D023822:Tissue Engineering; D016212:Transforming Growth Factor beta
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes; D016212:Transforming Growth Factor beta; D011098:Polyglactin 910; D011092:Polyethylene Glycols