Development of cell-hybrid artificial bone: effect of osteogenic differentiation of bone marrow stromal stem cells on bone formation with newly developed interconnected porous calcium hydroxyapatite.

The purpose of this study was to evaluate the effect of osteogenic differentiation of bone marrow stromal stem cells (BMSCs) on bone formation in a novel interconnected porous calcium hydroxyapatite (IP-CHA). BMSCs/IP-CHA composites, as a cell-hybrid artificial bone, were made by injecting BMSCs solution into IP-CHA scaffolds. To induce osteogenic differentiation, BMSCs/IP-CHA composites were subcultured for three, seven, 10, and 14 days. At the end of each subculture period, BMSCs/IP-CHA composites were examined by SEM and ALP staining. BMSCs/IP-CHA composites of different osteogenic groups of subculture were also placed into bone sockets in the right femur of beagle dogs. After four weeks, same placement procedure was done in the left femur. BMSCs/IP-CHA subcultured for 10 and 14 days were ALP-positive as opposed to those of three and seven days. At four weeks after placement, bone formation was superior at the 10- and 14-day subculture groups. Based on the results obtained, it was suggested that osteogenic differentiation periods with 10 and 14 days of subculture for BMSCs/IP-CHA as a cell-hybrid artificial bone were beneficial in promoting bone formation.

Low-intensity pulsed ultrasound increases bone ingrowth into porous hydroxyapatite ceramic.

Synthetic porous ceramic made of hydroxyapatite (HA) has been used as a bone graft substitute. In the present study we investigated whether low-intensity pulsed ultrasound (LIPUS) accelerates bone ingrowth into the pores of HA ceramic. Application of LIPUS did not mechanically weaken porous ceramic that was immersed in water in vitro. In vivo experiments using rabbits showed that LIPUS application for 2 weeks significantly increased osteoblast number and bone area in the central part of the porous HA ceramic implanted in the femoral condyle in comparison with similarly implanted HA ceramic that was not exposed to LIPUS. LIPUS application for 3 weeks significantly increased mineralized tissue volume and mineral content in the porous HA ceramic. Wound healing assays revealed increased migration of MC3T3-E1 cells as a result of LIPUS treatment, partly accounting for the increased osteoblast number. Use of porous HA ceramic combined with LIPUS may be a promising treatment for filling large bone defects in a clinical setting.