title: Bone healing by sterilizable calcium phosphate tetrapods eluting osteogenic molecules.
abstract: Although bone grafts and prosthetic implants have shown some clinical success in the treatment of bone defects, the graft availability, biocompatibility, function, and longevity still remain to be improved. One possible solution to these problems is to develop bone implants acting on host cells to induce rapid bone regeneration. Here, we demonstrate bone healing by means of a sterilizable and osteogenic molecule-eluting implant system in which two small molecules, a smoothened agonist (SAG) and a helioxanthin derivative (TH), are loaded onto tetrapod-shaped calcium phosphate granules (Tetrabone). We succeeded in directing progenitor cells toward mature osteoblasts with the combined application of the two small molecules acting on different stages of osteogenesis. Tetrabone released SAG and TH for prolonged periods when loaded with these molecules. EOG sterilization did not affect the osteogenic activity of the SAG- and TH-loaded Tetrabones. The combinatorial use of SAG- and TH-loaded Tetrabones achieved bone healing without cell transplantation in a rat femur bone defect model within two weeks. This system will allow us to vary the combination rate of implants loaded with different osteogenic factors depending on the types and sizes of defects, potentially allowing full temporal and spatial control of the bone regeneration.
authors.affiliation: Department of Sensory and Motor System Medicine, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Maeda
authors.forename: Hironori
authors.initials: H
authors.lastname: Hojo
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shimohata
authors.forename: Sungjin
authors.initials: S
authors.lastname: Choi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Takato
authors.forename: Ung-il
authors.initials: UI
authors.lastname: Chung
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Ohba
mesh_terms: D000818:Animals; D002130:Calcium Phosphates / Q000494:pharmacology*; D002460:Cell Line; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology*; D020007:Implants, Experimental; D017705:Lignans / Q000494:pharmacology; D008297:Male; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects*; D011859:Radiography; D051381:Rats; D017208:Rats, Wistar; D013242:Sterilization; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D002130:Calcium Phosphates; D017705:Lignans; C505802:helioxanthin; C020243:calcium phosphate