1. Heterobifunctional poly(ethylene glycol)-tethered bone morphogenetic protein-2-stimulated bone marrow mesenchymal stromal cell differentiation and osteogenesis
- Author
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I-Hsuan Lin, Ging-Ho Hsiue, Hsia-Wei Liu, Chih Hwa Chen, and Ching-Lin Tsai
- Subjects
Pluripotent Stem Cells ,Poly ethylene glycol ,animal structures ,Stromal cell ,Cell Culture Techniques ,Bone Morphogenetic Protein 2 ,Mitosis ,Stimulation ,Bone Marrow Cells ,Bone morphogenetic protein 2 ,Polyethylene Glycols ,Drug Delivery Systems ,Microscopy, Electron, Transmission ,Osteogenesis ,Transforming Growth Factor beta ,medicine ,Animals ,Humans ,Polyglactin 910 ,Cells, Cultured ,Bioprosthesis ,Tissue Engineering ,Chemistry ,Mesenchymal stem cell ,General Engineering ,Cell Differentiation ,Mesenchymal Stem Cells ,Cell biology ,Bone morphogenetic protein 7 ,Bone morphogenetic protein 6 ,medicine.anatomical_structure ,embryonic structures ,Bone Morphogenetic Proteins ,Bone Substitutes ,Microscopy, Electron, Scanning ,Bone marrow ,Rabbits ,Biomedical engineering - 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.
- Published
- 2007