title: Recombinant human bone morphogenetic protein 2 (rhBMP-2) immobilized on laser-fabricated 3D scaffolds enhance osteogenesis.
abstract: The regeneration of bone via a tissue engineering approach involves components from the macroscopic to the nanoscopic level, including appropriate 3D scaffolds, cells and growth factors. In this study, hexagonal scaffolds of different diagonals were fabricated by Direct Laser Writing using a photopolymerizable hybrid material. The proliferation of bone marrow (BM) mesenchymal stem cells (MSCs) cultured on structures with various diagonals, 50, 100, 150 and 200μm increased significantly after 10days in culture, however without significant differences among them. Next, recombinant human bone morphogenetic protein 2 (rhBMP-2) was immobilized onto the hybrid material both via covalent binding and physical adsorption. Both immobilization types exhibited similar high releaseate bioactivity profiles and a sustained delivery of rhBMP-2. The collagen and calcium levels produced in the extracellular matrix (ECM) were significantly elevated for the samples functionalized with BMP-2 compared to those in the osteogenic medium. Furthermore, significant upregulation of gene expression in both types of BMP-2 immobilized scaffolds was observed for alkaline phosphatase (ALPL) and osteocalcin (BGLAP) at days 7, 14, and 21, for RUNX2 at day 21, and for osteonectin (SPARC) at days 7 and 14. The results suggest that the release of bioactive rhBMP-2 from the hybrid scaffolds enhance the control over the osteogenic differentiation during cell culture.
authors: Department of Materials Science and Technology, University of Crete, Greece; Institute of Electronic Structure and Laser (IESL), Foundation for Research and Technology Hellas (FORTH), Greece. Electronic address: mchatzin@materials.uoc.gr.
authors: Maria
authors: M
authors: Chatzinikolaidou
authors: Heamatology Laboratory, School of Medicine, University of Crete, Greece.
authors: Charalampos
authors: C
authors: Pontikoglou
authors: Institute of Electronic Structure and Laser (IESL), Foundation for Research and Technology Hellas (FORTH), Greece.
authors: Konstantina
authors: K
authors: Terzaki
authors: Department of Materials Science and Technology, University of Crete, Greece; Institute of Electronic Structure and Laser (IESL), Foundation for Research and Technology Hellas (FORTH), Greece.
authors: Maria
authors: M
authors: Kaliva
authors: Heamatology Laboratory, School of Medicine, University of Crete, Greece.
authors: Athanasia
authors: A
authors: Kalyva
authors: Heamatology Laboratory, School of Medicine, University of Crete, Greece.
authors: Eleni
authors: E
authors: Papadaki
authors: Department of Materials Science and Technology, University of Crete, Greece; Institute of Electronic Structure and Laser (IESL), Foundation for Research and Technology Hellas (FORTH), Greece.
authors: Maria
authors: M
authors: Vamvakaki
authors: Institute of Electronic Structure and Laser (IESL), Foundation for Research and Technology Hellas (FORTH), Greece.
authors: Maria
authors: M
authors: Farsari
mesh_terms: D000327:Adsorption; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D055767:Immobilized Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D007834:Lasers; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics; D015676:Osteonectin / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; D055767:Immobilized Proteins; D015676:Osteonectin; C493709:RUNX2 protein, human; D011994:Recombinant Proteins; D015675:Osteocalcin; D003094:Collagen; D000469:Alkaline Phosphatase
keywords: Bone tissue engineering; Hybrid 3D scaffolds; Osteogenic differentiation; Two-photon polymerization; rhBMP-2