title: Effect of cell-seeded hydroxyapatite scaffolds on rabbit radius bone regeneration.
abstract: Highly porous hydroxyapatite (HA) scaffolds were developed as bone graft substitutes using a template coating process, characterized, and seeded with bone marrow-derived mesenchymal stem cells (BMSCs). To test the hypothesis that cell-seeded HA scaffolds improve bone regeneration, HA scaffolds without cell seeding (HA-empty), HA scaffolds with 1.5 × 10(4) BMSCs (HA-low), and HA scaffolds with 1.5 × 10(6) BMSCs (HA-high) were implanted in a 10-mm rabbit radius segmental defect model for 4 and 8 weeks. Three different fluorochromes were administered at 2, 4, and 6 weeks after implantation to identify differences in temporal bone growth patterns. It was observed from fluorescence histomorphometry analyses that an increased rate of bone infiltration occurred from 0 to 2 weeks (p < 0.05) of implantation for the HA-high group (2.9 ± 0.5 mm) as compared with HA-empty (1.8 ± 0.8 mm) and HA-low (1.3 ± 0.2 mm) groups. No significant differences in bone formation within the scaffold or callus formation was observed between all groups after 4 weeks, with a significant increase in bone regenerated for all groups from 4 to 8 weeks (28.4% across groups). Although there was no difference in bone formation within scaffolds, callus formation was significantly higher in HA-empty scaffolds (100.9 ± 14.1 mm(3) ) when compared with HA-low (57.8 ± 7.3 mm(3) ; p ≤ 0.003) and HA-high (69.2 ± 10.4 mm(3) ; p ≤ 0.02) after 8 weeks. These data highlight the need for a better understanding of the parameters critical to the success of cell-seeded HA scaffolds for bone regeneration.
authors.affiliation: Extremity Trauma and Regenerative Medicine, U.S. Army Institute of Surgical Research, Ft. Sam Houston, Texas.
authors.forename: C R
authors.initials: CR
authors.lastname: Rathbone
authors.forename: T
authors.initials: T
authors.lastname: Guda
authors.forename: B M
authors.initials: BM
authors.lastname: Singleton
authors.forename: D S
authors.initials: DS
authors.lastname: Oh
authors.forename: M R
authors.initials: MR
authors.lastname: Appleford
authors.forename: J L
authors.initials: JL
authors.lastname: Ong
authors.forename: J C
authors.initials: JC
authors.lastname: Wenke
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D002146:Bony Callus / Q000187:drug effects / Q000473:pathology; D002113:Calcification, Physiologic / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D017886:Durapatite / Q000494:pharmacology*; D005260:Female; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D011817:Rabbits; D011884:Radius / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D054457:Tissue Scaffolds / Q000737:chemistry*; D055114:X-Ray Microtomography
chemical_list: D005456:Fluorescent Dyes; D017886:Durapatite
keywords: bone; callus; hydroxyapatite; mesenchymal stem cells; rabbit radius