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Hyaluronic acid (HA) and fibrin glue (FG) are effective hydrogels for tissue engineering applications as they support tissue in-growth, retain growth factors, and release them slowly with time. The scaffolds, in combination with a hydrogel, effectuate a successful graft. However, the survival of a graft entirely depends upon a functional vascular supply. Therefore, hydrogels must support the in-growing vasculature. To study and compare the vascular patterns, HA and FG hydrogel-containing PLDLLA-TCP-PCL scaffolds were implanted in the groin of male Lewis rats and supplied with a micro-surgically prepared arterio-venous (A-V) loop. The rats were perfused with a vascular contrast media after 4 and 8 weeks and sacrificed for further analysis. The specimens were scanned with micro-CT to find the vascular growth patterns. Corrosion casting of blood vessels followed by SEM demonstrated a high vascular density near the parent blood vessels. Histologically, HA and FG implanted animal groups showed significant angiogenetic activity, especially within the pores of the scaffold. However, formation of new blood vessels was more conspicuously observed at 4 weeks in FG than HA implants. Furthermore, by 8 weeks, the number and pattern of blood vessels were comparable between them. At this time, HA was still present indicating its slow degradation. The finding was confirmed by histomorphometric analysis. This experimental study demonstrates that HA containing composite scaffold systems permit stabile in-growth of blood vessels due to sustained degradation over 8 weeks. HA is a potential matrix for a tissue engineered composite graft. [ABSTRACT FROM PUBLISHER]

The major blood supply to long bones occurs through the nutrient arteries, which enter through the nutrient foramina. This supply is essential during the growing period, during the early phases of ossification, and in procedures such as bone grafts, tumor resections, traumas, congenital pseudoarthrosis, and in transplant techniques in orthopedics. The present study analyzed the location and the number of nutrient foramina in the diaphysis of 885 long bones of the upper and lower limbs of adults: 174 humeri, 157 radii, 146 ulnae, 152 femora, 142 tibiae and 114 fibulae. The location of the nutrient foramina is predominant on the anterior aspect of the upper limb long bones, and on the posterior aspect of the lower limb long bones. The majority of the bones studied had a single nutrient foramen, which may represent a single source of blood supply. The mean foraminal index for the upper limb bones was 55.2% for the humerus, 35.7% for the radius, and 37.9% for the ulna, and for the lower limb bones, 43.7% for the femur. 32.7% for the tibia and 46.1% for the fibula. This study recorded data related to the population of Southern Brazil, providing ethnic data to be used for comparison and that may help in surgical procedures and in the interpretation of radiological images. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: An anti-angiogenic effect of bisphosphonates has been reported in different experimental models. Zoledronic acid is currently administered in osteoporotic patients as a single 5 mg injection once a year and its vascular effect in bone has not been yet evaluated. Materials and methods: The vascular dose effect of a single injection of zoledronic acid was evaluated on healing vascularization developed under a bone chamber implanted on the calvaria of 30 rats. After 3 weeks of healing, the rats were randomized into 3 groups receiving an injection of either physiologic saline solution (PSS) or zoledronic acid tested at  120 μg/kg, the equivalent of a 5 mg dose of zoledronic acid in humans (Z120), and  400 μg/kg, a supra-pharmacologic dose (Z400). A longitudinal follow-up of the healing vascular network was carried out at days (D) 1, 3, 6, 9, 12, 15 and 28 after injection by intravital imaging. Variations in vascular density, total length of the vascular network and mean diameter of vascular network branches were determined by image analysis (Aphelion® software). Results: A decrease was observed in both vascular density and total length of the network in control and treated groups (time effect). No difference in variation in vascular density was observed between the PSS group and the Z120 group at any time point (p =NS). A trend to a higher decrease in vascular density was noted between D12 and D15 in the Z400 group. A significant decrease in total length was noted at D15 in the Z400 group (p =0.03) compared to the PSS group, whereas no change was noted in rats treated with  120 μg/kg compared to PSS rats on any of the follow-up days (p =0.2). No variation in mean diameter of vascular network branches was noted in any of the three groups at any of the follow-up days (p =0.53). Conclusion: A single injection of clinically relevant dosing regimens of zoledronic acid may not have a notable impact on vascularization in bone sites. The anti-angiogenic effect of bisphosphonates seems to express itself, in our model, at higher doses than those used in patients treated for osteoporosis. [Copyright &y& Elsevier]

Bone formation in a variety of contexts depends on angiogenesis; however, there are few reports of the vascular response to osteogenic skeletal loading. We used the rat forelimb compression model to characterize vascular changes after fatigue loading. The right forelimbs of 72 adult rats were loaded cyclically in vivo to one of four displacement levels, to produce four discrete levels of ulnar damage. Rats were killed 3-14 days after loading, and their vasculature was perfused with silicone rubber. Transverse histological sections were cut along the ulnar diaphysis. We quantified vessel number, average vessel area, total vessel area, and bone area. On day 3, we observed a dramatic periosteal expansion near the ulnar midshaft, with significant increases in periosteal vascularity; total vessel area was increased 250-450% (P < 0.001). Vascularity remained elevated on days 7 and 14. Vessel number and average vessel area were not correlated (P = 0.09) and contributed independently to total vascular increases. Bone area was not increased on day 3 but on days 7 and 14 was increased significantly in all displacement groups (P < 0.01) due to periosteal woven bone formation. Vascular and bone changes depended on longitudinal location (P < 0.001), with peak increases 2 mm distal to the midshaft. Vascular and bone changes also depended on displacement level (P < 0.005), with greater increases at higher levels of fatigue displacement. We conclude that skeletal fatigue loading induces a rapid increase in periosteal vascularity, followed by an increase in bone area. The angiogenic-osteogenic response is spatially coordinated and scaled to the level of the mechanical stimulus. [ABSTRACT FROM AUTHOR]