title: Surface modification with fibrin/hyaluronic acid hydrogel on solid-free form-based scaffolds followed by BMP-2 loading to enhance bone regeneration.
abstract: Bone tissue engineering often requires a well-defined scaffold that is highly porous. The multi-head deposition system (MHDS), a form of solid freeform fabrication, has raised great interest as a method for fabricating scaffolds, since it yields a highly porous inter-connective structure without the use of cytotoxic solvents, and permits the diffusion of nutrients and oxygen. However, this method is not suitable for introducing proteins, as it includes a heating process. Hydrogels incorporated with protein coating of the scaffold surface could overcome this MHDS limitation. In the present study, the surface of a scaffold fabricated using MHDS was coated with a mixture of fibrin and hyaluronic acid (HA) and used as a vehicle for delivery of both bone morphogenetic protein-2 (BMP-2) and adipose-derived stromal cells (ASCs). Fibrin/HA coating of the scaffold significantly enhanced initial cell attachment. Furthermore, the in vitro release of BMP-2 from fibrin/HA-coated scaffolds was sustained for 3 days and it stimulated the alkaline phosphatase activity of ASCs seeded on the scaffold for 10 days more actively and continuously than did the soluble BMP-2 that was added to the culture media, not the scaffold itself. Importantly, the transplantation of undifferentiated ASCs inoculated on BMP-2-loaded, fibrin/HA-coated scaffolds resulted in more improved bone formation and mineralization than did the transplantation of undifferentiated ASCs seeded on uncoated scaffolds or on fibrin/HA-coated scaffolds without BMP-2, but containing BMP-2 in the cell suspension medium. These results show that BMP-2-loaded, fibrin/HA-coated scaffolds fabricated using MHDS may be useful in stimulating bone regeneration from undifferentiated ASCs in vivo.
authors.affiliation: Department of Biomedical Science, CHA University, Seoul, Republic of Korea.
authors.forename: Sun-Woong
authors.initials: SW
authors.lastname: Kang
authors.forename: Jin-Su
authors.initials: JS
authors.lastname: Kim
authors.forename: Kwang-Sook
authors.initials: KS
authors.lastname: Park
authors.forename: Byung-Hyun
authors.initials: BH
authors.lastname: Cha
authors.forename: Jin-Hyung
authors.initials: JH
authors.lastname: Shim
authors.forename: Jong Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Dong-Woo
authors.initials: DW
authors.lastname: Cho
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Rhie
authors.forename: Soo-Hong
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry* / Q000494:pharmacology*; D016466:CHO Cells; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D005337:Fibrin / Q000737:chemistry*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D055396:Bone Morphogenetic Protein 2; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D005337:Fibrin; D006820:Hyaluronic Acid