A bone fluid flow hypothesis for muscle pump-driven capillary filtration: ii proposed role for exercise in erodible scaffold implant incorporation

Winet, Howard

doi:10.22203/ecm.v006a01

Cited by 21 publications

(15 citation statements)

References 92 publications

(70 reference statements)

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“…Whether and how changes in mechanical loading and/or IMP may affect bone blood circulation and the tone of the intramedullary blood vessel is not clear (99), but it is likely that muscle contraction plays a role through the modulation of vascular resistance regulation the flow of blood exiting bone (102)(103). Further research in this area is required to understand whether skeletal blood perfusion and mechanoadaptation to exerciseinduced bone strain may induce synergistic effects on bone formation.…”

Section: Mechanoadaptation Of Bone and The Blood Supplymentioning

confidence: 99%

The Key Role of the Blood Supply to Bone

2013

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The importance of the vascular supply for bone is well-known to orthopaedists but is still rather overlooked within the wider field of skeletal research. Blood supplies oxygen, nutrients and regulatory factors to tissues, as well as removing metabolic waste products such as carbon dioxide and acid. Bone receives up to about 10% of cardiac output, and this blood supply permits a much higher degree of cellularity, remodelling and repair than is possible in cartilage, which is avascular. The blood supply to bone is delivered to the endosteal cavity by nutrient arteries, then flows through marrow sinusoids before exiting via numerous small vessels that ramify through the cortex. The marrow cavity affords a range of vascular niches that are thought to regulate the growth and differentiation of hematopoietic and stromal cells, in part via gradients of oxygen tension. The quality of vascular supply to bone tends to decline with age and may be compromised in common pathological settings, including diabetes, anaemias, chronic airway diseases and immobility, as well as by tumours. Reductions in vascular supply are associated with bone loss. This may be due in part to the direct effects of hypoxia, which blocks osteoblast function and bone formation but causes reciprocal increases in osteoclastogenesis and bone resorption. Common regulatory factors such as parathyroid hormone or nitrates, both of which are potent vasodilators, might exert their osteogenic effects on bone via the vasculature. These observations suggest that the bone vasculature will be a fruitful area for future research.

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Section: Mechanoadaptation Of Bone and The Blood Supplymentioning

confidence: 99%

The Key Role of the Blood Supply to Bone

2013

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“…For the generation of bone tissue, it appears that bone cells in vivo are subjected mainly to fluid shear stress, from mainly two kinds of fluid profile at the cellular level: an outward radial unidirectional flow driven by a hydrostatic pressure drop across the cortex (McAllister et al, 2000;Winet, 2003) and an oscillatory flow induced by mechanical loading (Cowin et al, 1995;Kufahl and Saha, 1990;Rubin et al, 2006;Weinbaum et al, 1994;Zhang et al, 2007). Two-dimensional flow chamber studies have shown that the shear stress induced by unidirectional flow could elicit a flow-induced osteogenenic response from bone cells by increasing ALP activity (Jessop et al, 2002;Kapur et al, 2003;McAlliste and Frangos, 1999;Pavalko et al, 1998), and the expression of osteocalcin (Lan et al, 2003), osteopontin (Kreke and Goldstein, 2004), and bone sialoprotein (Kreke et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

3D culture of osteoblast‐like cells by unidirectional or oscillatory flow for bone tissue engineering

Furukawa

Ushida

2009

Biotech & Bioengineering

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A medium perfusion system is expected to be beneficial for three-dimensional (3D) culture of engineered bone, not only by chemotransport enhancement but also by mechanical stimulation. In this study, perfusion systems with either unidirectional or oscillatory medium flow were developed, and the effects of the different flow profiles on 3D culturing of engineered bone were studied. Mouse osteoblast-like MC 3T3-E1 cells were 3D-cultured with porous ceramic scaffolds in vitro for 6 days under static and hydrodynamic conditions with either a unidirectional or oscillatory flow. We found that, in the static culture, the cells proliferated only on the scaffold surfaces. In perfusion culture with the unidirectional flow, the proliferation was significantly higher than in the other groups but was very inhomogeneous, which made the construct unsuitable for transplantation. Only the oscillatory flow allowed osteogenic cells to proliferate uniformly throughout the scaffolds, and also increased the activity of alkaline phosphatase (ALP). These results suggested that oscillatory flow might be better than unidirectional flow for 3D construction of cell-seeded artificial bone. The oscillatory perfusion system could be a compact, safe, and efficient bioreactor for bone tissue engineering.

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“…In addition, appositional fronts along the bone surfaces have been said to demonstrate centrifugal interstitial fluid movement from the medullary canal to the periosteal surface [5,6,[9][10][11]15,16,19,26]. The purpose of this study was to analyze the effect of different histological processes that could lead to the presence of ferritin in the mineralized matrix and the characteristic ferritin halo labeling previously demonstrated by other investigators.…”

Section: Discussionmentioning

confidence: 91%

“…However, other investigators have shown that ferritin forms halo-shaped labeling that appears to enter the mineralized matrix around blood vessels, along with appositional fronts along the bone surfaces [5,15,16,19]. This ferritin labeling is widely used to explain normal interstitial fluid movement in bone: the halos are said to demonstrate bulk centrifugal interstitial fluid movement away from a highly pressurized vascular porosity, and the appositional fronts are said to demonstrate centrifugal interstitial fluid movement from the medullary canal to the periosteal surface [5,6,[9][10][11]15,16,19,26]. These previous studies suggest that ferritin may be small enough to pass through the canalicular pores and possibly through the collagenapatite pores in the mineralized matrix.…”

Section: Introductionmentioning

confidence: 99%

Mapping bone interstitial fluid movement: Displacement of ferritin tracer during histological processing

Ciani¹,

Doty²,

Fritton³

2005

Bone

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Bone interstitial fluid flow is thought to play a fundamental role in the mechanical stimulation of bone cells, either via shear stresses or cytoskeletal deformations. Recent evidence indicates that osteocytes are surrounded by a fiber matrix that may be involved in the mechanotransduction of external stimuli as well as in nutrient exchange. In our previous tracer studies designed to map how different-sized molecules travel through the bone porosities, we found that injected ferritin was confined to blood vessels and did not pass into the mineralized matrix. However, other investigators have shown that ferritin forms halo-shaped labeling that enters the mineralized matrix around blood vessels. This labeling is widely used to explain normal interstitial fluid movement in bone; in particular, it is said to demonstrate bulk centrifugal interstitial fluid movement away from a highly pressurized vascular porosity. In addition, appositional ferritin fronts are said to demonstrate centrifugal interstitial fluid movement from the medullary canal to the periosteal surface. The purpose of this study was to investigate the conflicting ferritin labeling results by evaluating the role of different histological processes in the formation of ferritin "halos." Ferritin was injected into the rat vasculature and allowed to circulate for 5 min. Samples obtained from tibiae were reacted for different times with Perl's reagent and then were either paraffin-embedded or sectioned with a cryostat. Halo-like labeling surrounding vascular pores was found in all groups, ranging from 1.2-3.9% for the samples treated with the shortest histological processes (unembedded, frozen sections) to 5.6-15% for the samples treated with the longest histological processes (paraffin-embedded sections). These results indicate that different histological processing methods are able to create ferritin "halos," with some processing methods allowing more redistribution of the ferritin tracer than others. Based on these results and the fact that "halo" labeling has not been found with any other tracer, as we seek to further delineate the movement of interstitial fluid and the role it plays in bone mechanotransduction, we believe that ferritin "halo" labeling should not be used to demonstrate physiological bone interstitial fluid flow.

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A bone fluid flow hypothesis for muscle pump-driven capillary filtration: ii proposed role for exercise in erodible scaffold implant incorporation

Cited by 21 publications

References 92 publications

The Key Role of the Blood Supply to Bone

The Key Role of the Blood Supply to Bone

3D culture of osteoblast‐like cells by unidirectional or oscillatory flow for bone tissue engineering

Mapping bone interstitial fluid movement: Displacement of ferritin tracer during histological processing

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