Читать книгу Bone and Soft Tissue Augmentation in Implantology - Группа авторов - Страница 24

Autografts contain viable osteoprogenitor cells, in contrast to allografts and bone substitutes of xenogeneic and synthetic origin. By definition, osteogenic means that the cells brought along during transplantation actively participate in bone formation, i.e. osteogenic precursor cells of the mesenchymal line differentiate into osteoblasts after transplantation and form new bone. Numerous in vitro studies have shown that osteogenic cells can be generated from explant cultures of bone grafts, particularly from trabecular but also from cortical bone.^56,115 The key experiment that proved osteogenicity related to transplantation at ectopic sites. This research took place in the 1970s, when Gray and Elves transplanted isografts from the ilium⁵² and femur diaphysis,⁵³ e.g. into the back of rats. They showed bone formation after 2 weeks, mainly originating from the transplanted endosteal and periosteal cells. Once the cells were removed by enzymatic digestion or through boiling, the osteogenic capacity was nil, suggesting that the osteocytes could not replace the cells on the surface and that the bone matrix alone could not induce bone formation.

In a xenogeneic transplantation model, 5 mm³ of human morselized cancellous bone from the proximal femur was transplanted into immunodeficient mice that received radiation, and depletion of macrophage and natural killer cells. Consistently, after 8 weeks, new bone was produced by human bone cells rather than from the induction of host mesenchymal cells into mouse osteoblasts.¹³ Bone transplants, however, underwent resorption and necrosis in untreated immunodeficient mice, considering that macrophages could developed into osteoclasts.¹³ Also, in a goat model, ectopic transplantation of 1 cm³ of femur condylar corticocancellous bone was transplanted in the paraspinal muscle. Both the block grafts and the respective bone chips showed ectopic new bone formation after 12 weeks. Upon freeze thawing, block grafts maintained a weak osteogenic potential, while the respective bone chips were resorbed,⁷⁵ probably because only a few osteogenic cells can survive under such conditions.¹¹⁴ Preclinical research in goats showed that it requires a well-nourished environment for the transplanted osteogenic cells to contribute to bone formation.⁷⁴ Mouse models further revealed that perivascular cells located within transcortical channels contributed to osteoblast formation and bone tube closure in a cortical bone transplantation model.^97,123

Recent evidence further suggested that, at least in a mouse model, the interval between autograft harvesting and transplantation affected its viability and bone-forming capacity.¹¹⁹ Immediately after autograft harvesting, apoptotic cells were barely detectable, but already within 5 minutes the number of apoptotic cells had nearly tripled.¹¹⁹ The time between harvesting and transplantation also affected the osteogenic potential of an autograft upon transplantation.¹¹⁹ Overall, autografts resemble the osteogenic potential of tissue engineering constructs, showing ectopic bone formation; however, when in small-sized constructs, only around 20 to 70 mm³ in mice⁷⁹ and in goats.⁷⁶ Importantly, however, the orthotopic transplantation could not reveal any benefit of cell-based therapies with respect to bone formation at the defect site.⁷⁶ Thus, beside the fact that osteogenic cells can basically survive transplantation and are a source of osteoblasts at ectopic sites, the overall contribution of the transplanted cells to graft consolidation is yet to be investigated. Nevertheless, our biopsies suggest that the new bone originates from the transplanted bone chips, with new, nascent bone bridging the space between the transplanted bone particles (Fig 1-12).