title: Development of a bone reconstruction technique using a solid free-form fabrication (SFF)-based drug releasing scaffold and adipose-derived stem cells.
abstract: For tissue regeneration, three essential components of scaffolds, signals (biomolecules), and cells are required. Moreover, because bony defects are three-dimensional in many clinical circumstances, an exact 3D scaffold is important. Therefore, we proposed an effective reconstruction tool for cranial defects using human adipose-derived stem cells (hADSCs) and a 3D functional scaffold fabricated by solid free-form fabrication (SFF) technology that secretes biomolecules. We fabricated poly(propylene fumarate)-based 3D scaffolds with embedded microsphere-deliverable bone morphogenetic protein-2 (BMP-2) by microstereolithography. BMP-2-loaded SFF scaffolds with/without hADSCs (SFF/BMP/hADSCs scaffolds and SFF/BMP scaffolds, respectively) and BMP-2-unloaded SFF scaffolds (SFF scaffolds) were then implanted in rat crania, and in vivo bone formation was observed. Analyses of bone formation areas using micro-computed tomography (micro-CT) showed the superiority of SFF/BMP/hADSCs scaffolds. Hematoxylin and eosin stain, Masson's trichrome stain, and collagen type-I stain supported the results of the micro-CT scan. And human leukocyte antigen-ABC showed that seeded, differentiated hADSCs were well grown and changed to the bone tissue at the inside of the scaffold. Results showed that our combination of a functional 3D scaffold and hADSCs may be a useful tool for improving the reconstruction quality of severe bony defects in which thick bone is required.
authors.affiliation: Department of NanoEngineering, The University of California, San Diego, La Jolla, California 92093-0448, USA.
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Lee
authors.forename: Ki-Joo
authors.initials: KJ
authors.lastname: Kim
authors.forename: Kyung Shin
authors.initials: KS
authors.lastname: Kang
authors.forename: Shaochen
authors.initials: S
authors.lastname: Chen
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Rhie
authors.forename: Dong-Woo
authors.initials: DW
authors.lastname: Cho
mesh_terms: D020341:Absorbable Implants; D017667:Adipocytes / Q000502:physiology*; D001672:Biocompatible Materials; D015519:Bone Density / Q000502:physiology; D001846:Bone Development / Q000187:drug effects* / Q000502:physiology*; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology / Q000627:therapeutic use; D049109:Cell Proliferation; D002469:Cell Separation; D004396:Coloring Agents; D016503:Drug Delivery Systems; D006801:Humans; D007150:Immunohistochemistry; D008863:Microspheres; D016612:Paraffin Embedding; D012886:Skull / Q000002:abnormalities / Q000187:drug effects / Q000254:growth & development; D013234:Stem Cells / Q000502:physiology*; D050151:Subcutaneous Fat / Q000166:cytology; D023822:Tissue Engineering; D016707:Tissue Fixation; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D004396:Coloring Agents