Biomedical subjects

Susannah P Fritton

Publications and source records attributed to Susannah P Fritton.

6 recordsLinked to original sources

PubMed2005

Analysis of avian bone response to mechanical loading. Part two: Development of a computational connected cellular network to study bone intercellular communication.

Mechanical loading-induced signals are hypothesized to be transmitted and integrated by connected bone cells before reaching the bone surfaces where adaptation occurs. A computational connected cellular network (CCCN) model is developed to explore how bone cells perceive and transmit the signals through intercellular communication. This is part two of a two-part study in which a CCCN is developed to study the intercellular communication within a grid of bone cells. The excitation signal was computed as the loading-induced bone fluid shear stress in part one. Experimentally determined bone adaptation responses (Gross et al. in J Bone Miner Res 12:982-988, 1997 and Judex et al. in J Bone Miner Res 12:1737-1745, 1997) are correlated with the fluid shear stress by the CCCN, which adjusts cell sensitivities (loading and signal thresholds) and connection weights. Intercellular communication patterns extracted by the CCCN indicate the cell population responsible for perceiving the loading-induced signal, and loading threshold is shown to play an important role in regulating the bone response.

Algorithms↗

PubMed2005

Analysis of avian bone response to mechanical loading-Part one: Distribution of bone fluid shear stress induced by bending and axial loading.

Mechanical loading-induced signals are hypothesized to be transmitted and integrated by a bone-connected cellular network (CCN) before reaching the bone surfaces where adaptation occurs. Our objective is to establish a computational model to explore how bone cells transmit the signals through intercellular communication. In this first part of the study the bone fluid shear stress acting on every bone cell in a CCN is acquired as the excitation signal for the computational model. Bending and axial loading-induced fluid shear stress is computed in transverse sections of avian long bones for two adaptation experiments (Gross et al. in J Bone Miner Res 12:982-988, 1997 and Judex et al. in J Bone Miner Res 12:1737-1745, 1997). The computed fluid shear stress is found to be correlated with the radial strain gradient but not with bone formation. These results suggest that the radial strain gradient is the driving force for bone fluid flow in the radially distributed lacunar-canalicular system and that bone formation is not linearly related to the loading-induced local stimulus.

Animals↗

PubMed2005

Estimation of bone permeability using accurate microstructural measurements.

While interstitial fluid flow is necessary for the viability of osteocytes, it is also believed to play a role in bone's mechanosensory system by shearing bone cell membranes or causing cytoskeleton deformation and thus activating biochemical responses that lead to the process of bone adaptation. However, the fluid flow properties that regulate bone's adaptive response are poorly understood. In this paper, we present an analytical approach to determine the degree of anisotropy of the permeability of the lacunar-canalicular porosity in bone. First, we estimate the total number of canaliculi emanating from each osteocyte lacuna based on published measurements from parallel-fibered shaft bones of several species (chick, rabbit, bovine, horse, dog, and human). Next, we determine the local three-dimensional permeability of the lacunar-canalicular porosity for these species using recent microstructural measurements and adapting a previously developed model. Results demonstrated that the number of canaliculi per osteocyte lacuna ranged from 41 for human to 115 for horse. Permeability coefficients were found to be different in three local principal directions, indicating local orthotropic symmetry of bone permeability in parallel-fibered cortical bone for all species examined. For the range of parameters investigated, the local lacunar-canalicular permeability varied more than three orders of magnitude, with the osteocyte lacunar shape and size along with the 3-D canalicular distribution determining the degree of anisotropy of the local permeability. This two-step theoretical approach to determine the degree of anisotropy of the permeability of the lacunar-canalicular porosity will be useful for accurate quantification of interstitial fluid movement in bone.

Animals↗

PubMed2005

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

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.

Animals↗

PubMed2004

Delineating bone's interstitial fluid pathway in vivo.

Although interstitial fluid flow has been suggested to play a role in bone adaptation and metabolism, the constituents and ultrastructure of this interstitial fluid pathway are not well understood. Bone's lacunar-canalicular porosity is generally believed to be a continuous interstitial fluid pathway through which osteocytes sense external mechanical loading as well as obtain nutrients and dispose of wastes. Recent electron microscopy studies have suggested that a fiber matrix surrounds the osteocytic cell processes and fills this pericellular fluid space. However, studies injecting tracer molecules into the bone vasculature have provided conflicting results about the pore size or the fiber spacing of the interstitial fluid pathway. In addition, whether the smaller collagen-apatite porosity in adult bone is also a continuous fluid pathway is still unclear. To delineate bone's interstitial fluid pathway, four tracers of various size were injected into rats: reactive red (approximately 1 nm), microperoxidase (MP, approximately 2 nm), horseradish peroxidase (HRP, approximately 6 nm), and ferritin (approximately 10 nm). Five minutes after injection, the tibiae were harvested and processed using histological protocols optimized to minimize processing time to reduce possible redistribution of tracer molecules. The number of blood vessels and osteocytic lacunae labeled with the tracers per unit bone area was then measured for mid-diaphysial cross-sections of the tibia. While none of the tracers was detected within the mineralized bone matrix (the collagen-apatite porosity) using light microscopy, all the tracers except ferritin were found to pass through the canaliculi and appear in the osteocytic lacunae. These results indicate that while small tracers (<6 nm) readily pass through the lacunar-canalicular porosity in the absence of mechanical loading, there appears to be an upper limit or cutoff size between 6 and 10 nm for molecular movement from bone capillaries to osteocytic lacunae in rat long bone. This range of pore size contains the most likely fiber spacing (approximately 7 nm) that has been proposed for the lacunar-canalicular annular space based on the presence of a proteoglycan fiber matrix surrounding the osteocyte.

Animals↗

PubMed2003

On bone adaptation due to venous stasis.

This paper addresses the question of whether or not interstitial fluid flow due to the blood circulation accounts for the observed periosteal bone formation associated with comprised venous return (venous stasis). Increased interstitial fluid flow induced by increased intramedullary pressure has been proposed to account for the periosteal response in venous stasis. To investigate the shear stresses acting on bone cell processes due to the blood circulation-driven interstitial fluid flow, a poroelastic model is extended to the situation in which the interstitial fluid flow in an osteon is driven by the pulsatile extravascular pressure in the osteonal canal as well as by the applied cyclic mechanical loading. Our results show that under normal conditions, the pulsatile extravascular pressure in the osteonal canal due to cardiac contraction (10mm Hg at 2Hz) and skeletal muscle contraction (30mm Hg at 1Hz) induce peak shear stresses on the osteocyte cell processes that are two orders of magnitude lower than those induced by physiological mechanical loading (100 microstrain at 1Hz). In venous stasis the induced peak shear stress is reduced further compared to the normal conditions because, although the mean intramedullary pressure is increased, the amplitude of its pulsatile component is decreased. These results suggest that the interstitial fluid flow is unlikely to cause the periosteal bone formation in venous stasis. However, the mean interstitial fluid pressure is found to increase in venous stasis, which may pressurize the periosteum and thus play a role in periosteal bone formation.

Adaptation, Physiological↗