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An MSC Chemotactic and Bone-Replaceable PLGA Material Involving Chemokine Loading OCP for Orthopedic Bone Defect
Yasuaki Kuriyama1,2, Ryo Hamai1, Yu Mori2
1Division of Biomaterials Science and Engineering (Division of Craniofacial Function Engineering), Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Abstract:
This study investigated whether a composite consisting of octacalcium phosphate (OCP) and porous poly(lactide-co-glycolide) (PLGA) involving recombinant stromal-derived factor-1 (SDF-1) can be used to repair severe orthopedic bone defects. Four experiments were conducted: 1) analysis of loading and release of a model protein for SDF-1, cytochrome c for OCP/PLGA; 2) observation of the effect of SDF-1 on migration of mesenchymal stem cells (MSCs) in the presence of OCP/PLGA in vitro; 3) histomorphometry and immunohistochemistry of bone regeneration of OCP/PLGA/SDF-1 by its implantation into a 3 mm diameter rat femoral transcortical defect for 4 weeks; and 4) micro-CT analysis of the tissue and Fourier transform infrared (FTIR) spectroscopy using undecalcified specimens. The binding effects of cytochrome c and SDF-1 on 40 wt % OCP/PLGA were compared using OCP/PLGA with SDF-1 or cytochrome c prepared under saturated (S) and supersaturated (SS) conditions, containing low or high calcium and phosphate ion concentrations. The loading rates were higher in OCP/PLGA regardless of SS conditions than in PLGA, while the release rate was higher in OCP/PLGA loaded under SS conditions throughout the time, up to 168 h. MSC migration was most enhanced in the OCP/PLGA and loaded under SS conditions for up to 48 h. Bone regeneration was enhanced in OCP/PLGA loaded under SS conditions followed by S conditions and no SDF-1 loading of the OCP/PLGA for up to 4 weeks. Micro-CT and FTIR analyses suggested the material's biodegradation and new bone replacement, which was consistent with the histomorphometry. Osteocalcin-positive cells, tartrate-resistant acid phosphatase-positive cells, and C-X-C motif chemokine receptor type 4 positive cells were localized around the OCP/PLGA under SS conditions, corresponding to higher resorption of the OCP granules. The results suggest that OCP/PLGA involving SDF-1 may repair severe orthopedic bone defects.

