Marrow development and its relationship to bone formation in vivo: A histological study using an implantable titanium device in rabbits

During embryogenesis, the creation of marrow sinusoids is intimately related to the coupled processes of osteogenesis and osteoclastic resorption. We set out to further define the relationship between bone formation and marrow development by implanting an intraosseous titanium device into the tibiae of rabbits which permits the examination of bone formation under standardized and reproducible conditions as well as allowing repeated sampling of new bone. A hollow channel is incorporated into the device into which tissue can grow. The device was left in place for 6 weeks to allow osseous integration to occur, after which the initial rod of new tissue growth was removed and subsequent histological and immunohistological sequence of events observed over the next 7 weeks. Interpretation of its morphological changes was further aided by concurrent histomorphometric studies. Because the channel was in direct continuity with the marrow cavity and isolated from the endosteum, immediate marrow regeneration was expected, following dissolution of the blood clot. Instead, our studies indicated that hemopoietic marrow cells, including the erythroid and myeloid series as well as megakaryocytes, did not appear until 3 weeks after implantation of the chamber when the newly formed bone had been remodeled to form an expanded marrow cavity. This intraosseous device is a useful in vivo model for studying the development of bone marrow hemopoietic and nonhemopoietic stromal cells and our results confirm the previous observation that influx of marrow cellular elements follow the formation of bone during endochondral as well as intramembranous ossification.