Skeletal Blood Flow in Bone Repair and Maintenance

Abstract

Bone is a highly vascularized tissue, although this aspect of bone is often overlooked. In this article, the importance of blood flow in bone repair and regeneration will be reviewed. First, the skeletal vascular anatomy, with an emphasis on long bones, the distinct mechanisms for vascularizing bone tissue, and methods for remodeling existing vasculature are discussed. Next, techniques for quantifying bone blood flow are briefly summarized. Finally, the body of experimental work that demonstrates the role of bone blood flow in fracture healing, distraction osteogenesis, osteoporosis, disuse osteopenia, and bone grafting is examined. These results illustrate that adequate bone blood flow is an important clinical consideration, particularly during bone regeneration and in at-risk patient groups. IntroductionThe rate at which blood vessels deliver oxygen, nutrients, growth factors, and circulating cells to boneis tightly regulated as a function of blood pressure and vascularizaAll biological tissues, including bone, require vascular support to survive. However, a frequently overlooked feature of bone is its extensive vascular network. Many studies have demonstrated that the blood vessels in bone are necessary for nearly all skeletal functions, including development, homeostasis, and repair (1). In addition, blood vessels lost due to trauma are regenerated, and new bone tissue formed in response to injury is vascularized. As a consequence of this environment, the blood vessels in bone are highly active, not simply a passive source for the delivery of nutrients (2). Readers are referred to recent publications for more information about the active processes of the vasculature not covered in this review, including the vascular niche and hypoxia-driven signaling pathways (3-4). tion. Given that blood pressure is generally maintained, the number and size of blood vessels determines the local blood flow rate. These two factors are regulated through the processes of angiogenesis and vasomotor function, respectively. Although a variety of skeletal disorders are associated with general vascular dysfunction (5-7), this review will focus on the regulation of bone blood flow, through the number and size of vessels, during bone repair and regeneration. To introduce this topic, the skeletal vascular anatomy and techniques for measuring bone blood flow are briefly discussed. Blood supply in boneA dense vascular network delivers oxygen and nutrients to all 206 bones in the human body. In general, this requires a substantial portion of the total cardiac output. Experimental work in various animal species has demonstrated that a significant portion of the resting cardiac output is directed to the skeleton, likely between 10% and 15% (8-12).For some time, the blood flow pattern in bones has been described as primarily centrifugal: blood is supplied to the cortical bone through the nutrient arteries in the (Figure 1), and returned by the periosteal veins (13). Particularly in long bones, the vascular anatomy is well characterized, wi...

Surface modification of vascular endothelial growth factor-loaded silk fibroin to improve biological performance of ultra-high-molecular-weight polyethylene via promoting angiogenesis

“…53 Although the exact permissible motion value for UHMWPE is still unknown, it was suggested that the orderly anchoring collagen I fibers binded graft strongly to bones such that there was minimal movement between the implant and host tissue. In contrast, although there was no new bone formation, VEGF promoted the angiogenesis so that the vascular networks support the metabolic demands of repair and the influx of cells providing osteogenic cues, 54 which is adverse to the activity of osteoclasts. 55 The graft choice for ACL reconstruction is the focus of attention in sports medicine.…”

Non-contact scanning diffuse correlation tomography system for three-dimensional blood flow imaging in a murine bone graft model

“…Allografts, however, result in 60% 10-year post-implantation failure rates due to poor integration and remodeling into host tissue, which is due in part to poor vascularization [3][4][5]. Blood flow is important for multiple phases in bone healing since blood vessels deliver oxygen, nutrients, growth factors, and circulating cells to the graft sites [6]. However, skeletal blood flow has not been widely studied due to limitations with existing techniques.…”

“…However, skeletal blood flow has not been widely studied due to limitations with existing techniques. Labeled microsphere administration is generally considered the gold standard technique for blood flow quantification, but is regarded as experimentally difficult and requires sacrifice of animals [6]. Laser Doppler imaging is a non-invasive technique to measure two-dimensional blood flow, but is limited due to shallow penetration depths [7].…”

Structural Crosstalk between Crystallographic Anisotropy in Bone Tissue and Vascular Network Analyzed with a Novel Visualization Method

“…It is also known that angiogenesis is stimulated in response to bone injury, resulting in increased transportation of osteoprogenitor cells and increased bone formation, whereas bone disuse leads to a reduction of the blood supply, resulting in decreased bone mass. 9) Evaluating intraosseous vascularization with regard to bone microstructure is important for treatments aimed at the recovery of bone tissue anisotropy and also the development of biomedical materials to induce oriented bone tissue regeneration. Nevertheless, even the evaluation methods for intraosseous vascular structure are not well established.…”

“…4,9) In addition to the bone matrix consisting of collagen brils and BAp, osteocyte networks are also an interacting element for the vascular patterns, because osteocyte networks have direct connections to vasculatures, enabling the transportation of molecules to and from osteocytes throughout the body. 25) Osteocytes are known to act as a mechanosensor in bone tissue and transmit biomechanical signals to osteoclasts/osteoblasts through uid ow inside the osteocyte networks.…”