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.