The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.
If you have any questions or comments, please contact us.
PURPOSE - MRI of cortical bone has the potential to offer new information about fracture risk. Current methods are typically performed with 3D acquisitions, which suffer from long scan times and are generally limited to extremities. This work proposes using 2D UTE with half pulses for quantitatively mapping bound and pore water in cortical bone.
METHODS - Half-pulse 2D UTE methods were implemented on a 3T Philips Achieva scanner using an optimized slice-select gradient waveform, with preparation pulses to selectively image bound or pore water. The 2D methods were quantitatively compared with previously implemented 3D methods in the tibia in five volunteers.
RESULTS - The mean difference between bound and pore water concentration acquired from 3D and 2D sequences was 0.6 and 0.9 mol H/L (3 and 12%, respectively). While 2D pore water methods tended to slightly overestimate concentrations relative to 3D methods, differences were less than scan-rescan uncertainty and expected differences between healthy and fracture-prone bones.
CONCLUSION - Quantitative bound and pore water concentration mapping in cortical bone can be accelerated by 2 orders of magnitude using 2D protocols with optimized half-pulse excitation. Magn Reson Med 77:945-950, 2017. © 2017 International Society for Magnetic Resonance in Medicine.
© 2017 International Society for Magnetic Resonance in Medicine.
A flow-through sensing platform based on open-ended porous silicon (PSi) microcavity membranes that are compatible with integration in on-chip sensor arrays is demonstrated. Because of the high aspect ratio of PSi nanopores, the performance of closed-ended PSi sensors is limited by infiltration challenges and slow sensor responses when detecting large molecules such as proteins and nucleic acids. In order to improve molecule transport efficiency and reduce sensor response time, open-ended PSi nanopore membranes were used in a flow-through sensing scheme, allowing analyte solutions to pass through the nanopores. The molecular binding kinetics in these PSi membranes were compared through experiments and simulation with those from closed-ended PSi films of comparable thickness in a conventional flow-over sensing scheme. The flow-through PSi membrane resulted in a 6-fold improvement in sensor response time when detecting a high molecular weight analyte (streptavidin) versus in the flow-over PSi approach. This work demonstrates the possibility of integrating multiple flow-through PSi sensor membranes within parallel microarrays for rapid and multiplexed label-free biosensing.
Self-assembled polymer/porous silicon nanocomposites overcome intracellular and systemic barriers for in vivo application of peptide nucleic acid (PNA) anti-microRNA therapeutics. Porous silicon (PSi) is leveraged as a biodegradable scaffold with high drug-cargo-loading capacity. Functionalization with a diblock polymer improves PSi nanoparticle colloidal stability, in vivo pharmacokinetics, and intracellular bioavailability through endosomal escape, enabling PNA to inhibit miR-122 in vivo.
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Changes in the distribution of bone mineralization occurring with aging, disease, or treatment have prompted concerns that alterations in mineralization heterogeneity may affect the fracture resistance of bone. Yet, so far, studies assessing bone from hip fracture cases and fracture-free women have not reached a consensus on how heterogeneity in tissue mineralization relates to skeletal fragility. Owing to the multifactorial nature of toughening mechanisms occurring in bone, we assessed the relative contribution of heterogeneity in mineralization to fracture resistance with respect to age, porosity, and area fraction of osteonal tissue. The latter parameters were extracted from quantitative backscattered electron imaging of human cortical bone sections following R-curve tests of single-edge notched beam specimens to determine fracture toughness properties. Microstructural heterogeneity was determined as the width of the mineral distribution (bulk) and as the sill of the variogram (local). In univariate analyses of measures from 62 human donors (21 to 101 years), local but not bulk heterogeneity as well as pore clustering negatively correlated with fracture toughness properties. With age as covariate, heterogeneity was a significant predictor of crack initiation, though local had a stronger negative contribution than bulk. When considering all potential covariates, age, cortical porosity and area fraction of osteons explained up to 50% of the variance in bone׳s crack initiation toughness. However, including heterogeneity in mineralization did not improve upon this prediction. The findings of the present work stress the necessity to account for porosity and microstructure when evaluating the potential of matrix-related features to affect skeletal fragility.
Published by Elsevier Ltd.
Accurately predicting fracture risk in the clinic is challenging because the determinants are multi-factorial. A common approach to fracture risk assessment is to combine X-ray-based imaging methods such as dual-energy X-ray absorptiometry (DXA) with an online Fracture Risk Assessment Tool (FRAX) that includes additional risk factors such as age, family history, and prior fracture incidents. This approach still does not adequately diagnose many individuals at risk, especially those with certain diseases like type 2 diabetes. As such, this study investigated bound water and pore water concentrations (Cbw and Cpw) from ultra-short echo time (UTE) magnetic resonance imaging (MRI) as new predictors of fracture risk. Ex vivo cadaveric arms were imaged with UTE MRI as well as with DXA and high-resolution micro-computed tomography (μCT), and imaging measures were compared to both whole-bone structural and material properties as determined by three-point bending tests of the distal-third radius. While DXA-derived areal bone mineral density (aBMD) and μCT-derived volumetric BMD correlated well with structural strength, they moderately correlated with the estimate material strength with gender being a significant covariate for aBMD. MRI-derived measures of Cbw and Cpw had a similar predictive ability of material strength as aBMD but did so independently of gender. In addition, Cbw was the only imaging parameter to significantly correlate with toughness, the energy dissipated during fracture. Notably, the strength of the correlations with the material properties of bone tended to be higher when a larger endosteal region was used to determine Cbw and Cpw. These results indicate that MRI measures of Cbw and Cpw have the ability to probe bone material properties independent of bone structure or subject gender. In particular, toughness is a property of fracture resistance that is not explained by X-ray based methods. Thus, these MRI-derived measures of Cbw and Cpw in cortical bone have the potential to be useful in clinical populations for evaluating fracture risk, especially involving diseases that affect material properties of the bone beyond its strength.
Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
In addition to the loss in bone volume that occurs with age, there is a decline in material properties. To test new therapies or diagnostic tools that target such properties as material strength and toughness, a pre-clinical model of aging would be useful in which changes in bone are similar to those that occur with aging in humans. Toward that end, we hypothesized that similar to human bone, the estimated toughness and material strength of cortical bone at the apparent-level decreases with age in the male Fischer F344 rat. In addition, we tested whether the known decline in trabecular architecture in rats translated to an age-related decrease in vertebra (VB) strength and whether non-X-ray techniques could quantify tissue changes at micron and sub-micron length scales. Bones were harvested from 6-, 12-, and 24-month (mo.) old rats (n=12 per age). Despite a loss in trabecular bone with age, VB compressive strength was similar among the age groups. Similarly, whole-bone strength (peak force) in bending was maintained (femur) or increased (radius) with aging. There was though an age-related decrease in post-yield toughness (radius) and bending strength (femur). The ability to resist crack initiation was actually higher for the 12-mo. and 24-mo. than for 6-mo. rats (notch femur), but the estimated work to propagate the crack was less for the aged bone. For the femur diaphysis region, porosity increased while bound water decreased with age. For the radius diaphysis, there was an age-related increase in non-enzymatic and mature enzymatic collagen crosslinks. Raman spectroscopy analysis of embedded cross-sections of the tibia mid-shaft detected an increase in carbonate subsitution with advanced aging for both inner and outer tissue.
Published by Elsevier Inc.
The growing need for therapies to treat large cutaneous defects has driven recent interest in the design of scaffolds that stimulate regenerative wound healing. While many studies have investigated local delivery of biologics as a restorative approach, an increasing body of evidence highlights the contribution of the mechanical properties of implanted scaffolds to wound healing. In the present study, we designed poly(ester urethane) scaffolds using a templated-Fused Deposition Modeling (t-FDM) process to test the hypothesis that scaffolds with substrate modulus comparable to that of collagen fibers enhance a regenerative versus a fibrotic response. We fabricated t-FDM scaffolds with substrate moduli varying from 5 to 266 MPa to investigate the effects of substrate modulus on healing in a rat subcutaneous implant model. Angiogenesis, cellular infiltration, collagen deposition, and directional variance of collagen fibers were maximized for wounds treated with scaffolds having a substrate modulus (Ks = 24 MPa) comparable to that of collagen fibers. The enhanced regenerative response in these scaffolds was correlated with down-regulation of Wnt/β-catenin signaling in fibroblasts, as well as increased polarization of macrophages toward the restorative M2 phenotype. These observations highlight the substrate modulus of the scaffold as a key parameter regulating the regenerative versus scarring phenotype in wound healing. Our findings further point to the potential use of scaffolds with substrate moduli tuned to that of the native matrix as a therapeutic approach to improve cutaneous healing.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Water that is bound to bone's matrix is implied as a predictor of fracture resistance; however, bound water is an elusive variable to be measured nondestructively. To date, the only nondestructive method used for studying bone hydration status is magnetic resonance variants (NMR or MRI). For the first time, bone hydration status was studied by short-wave infrared (SWIR) Raman spectroscopy to investigate associations of mineral-bound and collagen-bound water compartments with mechanical properties. Thirty cortical bone samples were used for quantitative Raman-based water analysis, gravimetric analysis, porosity measurement, and biomechanical testing. A sequential dehydration protocol was developed to replace unbound (heat drying) and bound (ethanol treatment) water in bone. Raman spectra were collected serially to track the OH-stretch band during dehydration. Four previously identified peaks were investigated: I3220/I2949, I3325/I2949 and I3453/I2949 reflect status of organic-matrix related water (mostly collagen-related water) compartments and collagen portion of bone while I3584/I2949 reflects status of mineral-related water compartments and mineral portion of bone. These spectroscopic biomarkers were correlated with elastic and post-yield mechanical properties of bone. Collagen-water related biomarkers (I3220/I2949 and I3325/I2949) correlated significantly and positively with toughness (R(2)=0.81 and R(2)=0.79; p<0.001) and post-yield toughness (R(2)=0.65 and R(2)=0.73; p<0.001). Mineral-water related biomarker correlated significantly and negatively with elastic modulus (R(2)=0.78; p<0.001) and positively with strength (R(2)=0.46; p<0.001). While MR-based techniques have been useful in measuring unbound and bound water, this is the first study which probed bound-water compartments differentially for collagen and mineral-bound water. For the first time, we showed an evidence for contributions of different bound-water compartments to mechanical properties of wet bone and the reported correlations of Raman-based water measurements to mechanical properties underline the necessity for enabling approaches to assess these new biomarkers noninvasively in vivo to improve the current diagnosis of those who may be at risk of bone fracture due to aging and diseases.
Published by Elsevier Inc.
A versatile and scalable method for fabricating shape-engineered nano- and micrometer scale particles from mesoporous silicon (PSi) thin films is presented. This approach, based on the direct imprinting of porous substrates (DIPS) technique, facilitates the generation of particles with arbitrary shape, ranging in minimum dimension from approximately 100 nm to several micrometers, by carrying out high-pressure (>200 MPa) direct imprintation, followed by electrochemical etching of a sub-surface perforation layer and ultrasonication. PSi particles (PSPs) with a variety of geometries have been produced in quantities sufficient for biomedical applications (≫10 μg). Because the stamps can be reused over 150 times, this process is substantially more economical and efficient than the use of electron beam lithography and reactive ion etching for the fabrication of nanometer-scale PSPs directly. The versatility of this fabrication method is demonstrated by loading the DIPS-imprinted PSPs with a therapeutic peptide nucleic acid drug molecule, and by vapor deposition of an Au coating to facilitate the use of PSPs as a photothermal contrast agent.
Comprising ~20% of the volume, water is a key determinant of the mechanical behavior of cortical bone. It essentially exists in two general compartments: within pores and bound to the matrix. The amount of pore water-residing in the vascular-lacunar-canalicular space-primarily reflects intracortical porosity (i.e., open spaces within the matrix largely due to Haversian canals and resorption sites) and as such is inversely proportional to most mechanical properties of bone. Movement of water according to pressure gradients generated during dynamic loading likely confers hydraulic stiffening to the bone as well. Nonetheless, bound water is a primary contributor to the mechanical behavior of bone in that it is responsible for giving collagen the ability to confer ductility or plasticity to bone (i.e., allows deformation to continue once permanent damage begins to form in the matrix) and decreases with age along with fracture resistance. Thus, dehydration by air-drying or by solvents with less hydrogen bonding capacity causes bone to become brittle, but interestingly, it also increases stiffness and strength across the hierarchical levels of organization. Despite the importance of matrix hydration to fracture resistance, little is known about why bound water decreases with age in hydrated human bone. Using (1)H nuclear magnetic resonance (NMR), both bound and pore water concentrations in bone can be measured ex vivo because the proton relaxation times differ between the two water compartments, giving rise to two distinct signals. There are also emerging techniques to measure bound and pore water in vivo with magnetic resonance imaging (MRI). The NMR/MRI-derived bound water concentration is positively correlated with both the strength and toughness of hydrated bone and may become a useful clinical marker of fracture risk.