Human Periosteum‐Derived Cells Combined With Superporous Hydroxyapatite Blocks Used as an Osteogenic Bone Substitute for Periodontal Regenerative Therapy: An Animal Implantation Study Using Nude Mice

Abstract

A superporous (85%) hydroxyapatite (HA) block was recently developed to improve osteoconductivity, but it was often not clinically successful when used to treat periodontal osseous defects. The primary purpose of this study is to develop a clinically applicable tissue-engineered bone substitute using this HA block and human alveolar periosteum-derived cells. Commercially available superporous HA blocks were acid treated and subjected to a three-dimensional (3D) culture for periosteal cell cultivation. Cells in the pore regions of the treated HA block were observed on the fracture surface by scanning electron microscopy. After osteogenic induction, the cell-HA complexes were implanted subcutaneously in nude mice. Osteoid formation was histologically evaluated. Acid treatment enlarged the interconnections among pores, resulting in the deep penetration of periosteal cells. Under these conditions, cells were maintained for >2 weeks without appreciable cell death in the deep pore regions of the HA block. The cell-HA complexes that received in vitro osteogenic induction formed osteoids in pore regions of the treated HA blocks in vivo. In contrast, most pore regions in the non-pretreated, cell-free HA blocks that were evaluated in vivo remained cell free. Our findings suggest that an acid-treated HA block could function as a better scaffold for the 3D high-density culture of human periosteal cells in vitro, and this cell-HA complex had significant osteogenic potential at the site of implantation in vivo. Compared with the cell-free HA block, our cell-HA complex using periosteal cells, which are the most accessible for clinical periodontists, showed promising results as a bone substitute in periodontal regenerative therapy.