Enhanced bone formation in the vicinity of porous ß-TCP scaffolds exhibiting slow release of collagen-derived tripeptides.

It has been experimentally proven that orally ingested collagen-derived tripeptides (Ctp) are quickly absorbed in the body and effectively promote the regeneration of connective tissues including bone and skin. Ctp are capable to activate osteoblasts and fibroblasts, which eventually promotes tissue regeneration. Based on these findings, a hypothesis was formulated in this study that direct delivery of Ctp to bone defect would also facilitate tissue regeneration as well as oral administration. To test the hypothesis, we prepared a bone augmentation material with the ability to slowly release Ctp, and investigated its in vivo bone regeneration efficacy. The implant material was porous ß-tricalcium phosphate (ß-TCP) scaffold which was coated with a co-precipitated layer of bone-like hydroxyapatite and Ctp. The ß-TCP was impregnated with approximately 0.8%(w/w) Ctp. Then, the Ctp-modified ß-TCP was implanted into bone defects of Wistar rats to evaluate in vivo efficacy of Ctp directly delivered from the material to the bone defects. The control was pristine porous ß-TCP. In vitro tests showed that Ctp were steadily released from the co-precipitated layer for approximately two weeks. The Ctp-modified scaffolds significantly promoted new bone formation in vivo in their vicinity as compared with pristine ß-TCP scaffolds; 6 weeks after the implantation, Ctp-modified scaffolds promoted twice as much bone formation as the control implants. Consequently, we achieved the slow and steady release of Ctp, and found that direct delivery of Ctp from implant materials was effective for bone regeneration as well as oral administration. A ß-TCP scaffold capable of slowly releasing bone-enhancing substances significantly promoted bone formation.

Enhancement of mechanical strength and in vivo cytocompatibility of porous ß-tricalcium phosphate ceramics by gelatin coating.

BACKGROUND: In an attempt to prepare scaffolds with porosity and compressive strength as high as possible, we prepared porous ß-tricalcium phosphate (TCP) scaffolds and coated them with regenerative medicine-grade gelatin. The effects of the gelatin coating on the compressive strength and in vivo osteoblast compatibility were investigated. METHODS: Porous ß-TCP scaffolds were prepared and coated with up to 3 mass% gelatin, and then subjected to thermal cross-linking. The gelatin-coated and uncoated scaffolds were then subjected to compressive strength tests and implantation tests into bone defects of Wistar rats. RESULTS: The compressive strength increased by one order of magnitude from 0.45 MPa for uncoated to 5.1 MPa for gelatin-coated scaffolds. The osteoblast density in the internal space of the scaffold increased by 40 % through gelatin coating. CONCLUSIONS: Coating porous bone graft materials with gelatin is a promising measure to enhance both mechanical strength and biomedical efficacy at the same time.