Osteogenic differentiation of marrow stromal stem cells in porous hydroxyapatite ceramics

Bioactive materials such as hydroxyapatite ceramics (HA) are known to show a stable interfacial bond with tissues (the bone bonding property has been especially well documented). However, the biological phenomenon on the material surface that evoke bone bonding is not well documented. To address this issue, composites of porous HA and rat marrow cells were implanted into ectopic (subcutaneous) sites. At 3 weeks after implantation, active osteoblasts lining the HA surface initiated bone formation, primarily as mature bone (lamellar type). Gene expression study using Northern blot analysis of the composites showed that alkaline phosphatase (ALP) and bone Gla protein (BGP) mRNAs began to appear at 2 weeks and the level of BGP mRNA at 4 weeks was comparable to that of cancerous bone. However, HA implantation without marrow cells did not show bone formation and neither BGP nor ALP mRNA were detected. These results indicate that the HA surface is able to support cell differentiation (osteoblastic phenotype expression of marrow stromal stem cells), as well as cell coordination resulting in mature bone formation that bonds to the HA.