Abstract
The repair of bone defects caused by trauma, infection or tumor resection is a major clinical orthopedic challenge. The application of bone grafts in orthopedic procedures is associated with a problem of inadequate vascularization in the initial phase after implantation. Meanwhile, the survival of cells within the implanted graft and its integration with the host tissue is strongly dependent on nutrient and gaseous exchange, as well as waste product removal, which are effectuated by blood microcirculation. In the bone tissue, the vasculature also delivers the calcium and phosphate indispensable for the mineralization process. The critical role of vascularization for bone healing and function, led the researchers to the idea of generating a capillary-like network within the bone graft in vitro, which could allow increasing the cell survival and graft integration with a host tissue. New strategies for engineering pre-vascularized bone grafts, that apply the co-culture of endothelial and bone-forming cells, have recently gained interest. However, engineering of metabolically active graft, containing two types of cells requires deep understanding of the underlying mechanisms of interaction between these cells. The present review focuses on the best-characterized endothelial cells—human umbilical vein endothelial cells (HUVECs)—attempting to estimate whether the co-culture approach, using these cells, could bring us closer to development and possible clinical application of prevascularized bone grafts.
Highlights
The repair of bone defects caused by trauma, infection or tumor resection, remains a major clinical orthopedic challenge
This temporary loss of Vascular endothelial (VE)-cadherin from cell junction might be due to vascular endothelial growth factor (VEGF) stimulation, which was reported to be highly expressed in co-cultured BM-mesenchymal stem cells (MSCs) [63]
Since one of the earlier studies [86] on human umbilical vein endothelial cells (HUVECs) co-cultured with osteoblasts suggested the model of bilateral communication through the diffusible factors, there has been growing body of research supporting the existence of mutual relationships between these types of cells
Summary
The repair of bone defects caused by trauma, infection or tumor resection, remains a major clinical orthopedic challenge. The survival of cells within the implanted graft and its integration with the host tissue is strongly dependent on nutrient and oxygen exchange, as well as waste product removal, which are provided by blood microcirculation. The critical role of vascularization for bone functioning led the researchers to the idea of generating a capillary-like network within the bone graft in vitro, which could allow increasing the cell survival and graft integration with a host tissue. Angiogenesis instead describes the formation of new capillaries from pre-existing blood vessels, which includes the migration of endothelial cells from the “mother” vessel [10,16]. In the light of the above, a new strategy for engineering prevascularized bone grafts has been developed, that encompasses the co-culture of endothelial and bone-forming cells. We focus on the best-characterized endothelial cells—HUVECs—attempting to estimate whether the co-culture approach could bring us closer to development and effective clinical implementation of prevascularized bone grafts
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