RESUMEN
Advanced scaffolds used in tissue regenerating applications should be designed to address clinically relevant complications such as surgical site infection associated with surgical procedures. Recognizing that patient-specific scaffolds with local drug delivery capabilities are a promising approach, we combined 3D printing with traditional salt-leaching techniques to prepare a new type of scaffold with purposely designed macro- and micro-porosity. The dual macro/micro porous scaffolds of medical-grade polycaprolactone (mPCL) were characterized for their porosity, surface area, mechanical properties and degradation. The use of these scaffolds for local prophylactic release of Cefazolin to inhibit S. aureus growth was investigated as an example of drug delivery with this versatile platform. The introduction of microporosity and increased surface area allowed for loading of the scaffold using a simple drop-loading method of this heat-labile antibiotic and resulted in significant improvement in its release for up to 3â¯days. The Cefazolin released from scaffolds retained its bioactivity similar to that of fresh Cefazolin. There were no cytotoxic effects in vitro against 3â¯T3 fibroblasts at Cefazolin concentration of up to 100⯵g/ml and no apparent effects on blood clot formation on the scaffolds in vitro. This study therefore presents a novel type of scaffolds with dual macro- and micro-porosity manufactured by a versatile method of 3D printing combined with salt-leaching. These scaffolds could be useful in tissue regeneration applications where it is desirable to prevent complications using local delivery of drugs.
Asunto(s)
Antibacterianos , Cefazolina , Sistemas de Liberación de Medicamentos/métodos , Poliésteres , Impresión Tridimensional , Staphylococcus aureus/crecimiento & desarrollo , Células 3T3 , Animales , Antibacterianos/farmacocinética , Antibacterianos/farmacología , Cefazolina/química , Cefazolina/farmacocinética , Cefazolina/farmacología , Ratones , Poliésteres/química , Poliésteres/farmacologíaRESUMEN
Most measures of femoral neck strength derived using dual-energy X-ray absorptiometry or computed tomography (CT) assume the femoral neck is a cylinder with a single cortical thickness. We hypothesized that these simplifications introduce errors in estimating strength and that detailed analyses will identify new parameters that more accurately predict femoral neck strength. High-resolution CT data were used to evaluate 457 cross-sectional slices along the femoral neck of 12 postmortem specimens. Cortical morphology was measured in each cross-section. The distribution of cortical thicknesses was evaluated to determine whether the mean or median better estimated central tendency. Finite-element models were used to calculate the stresses in each cross-section resulting from the peak hip joint forces created during a sideways fall. The relationship between cortical morphology and peak bone stress along the femoral neck was analyzed using multivariate regression analysis. In all cross-sections, cortical thicknesses were non-normally distributed and skewed toward smaller thicknesses (p < 0.0001). The central tendency of cortical thickness was best estimated by the median, not the mean. Stress increased as the median cortical thickness decreased along the femoral neck. The median, not mean, cortical thickness combined with anterior-posterior diameter best predicted peak bone stress generated during a sideways fall (R(2) = 0.66, p < 0.001). Heterogeneity in the structure of the femoral neck determines the diversity of its strength. The median cortical thickness best predicted peak femoral neck stress and is likely to be a relevant predictor of femoral neck fragility.
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Cuello Femoral/anatomía & histología , Fenómenos Biomecánicos , Cuello Femoral/fisiología , Análisis de Elementos Finitos , HumanosRESUMEN
MINI-ABSTRACT: Study of postmortem samples of cortical bone from the trochanters of 12 Caucasian females revealed that tissue mineral density (TMD) and tissue elastic modulus correlate weakly within and between individuals. Other material properties need to be taken into account to more fully predict variation in tissue elastic modulus. INTRODUCTION: Bone is a composite material that varies in its material composition and structural organization at the macro-, micro-, and nano-scales. This hierarchical organization is essential for bone's resistance to crack initiation and propagation. We quantified the relationship between regional heterogeneity in TMD and tissue elastic modulus in cortical bone of the trochanter to determine whether TMD can be used as a predictor of tissue elastic modulus. METHODS: Measurements of tissue elastic modulus and hardness were made using nanoindentation at 5 × 20 indent points spaced 100 µm apart. TMD at the same location was computed from quantitative backscattered scanning electron microscopy imaging of cortical samples from trochanters obtained at postmortem from 12 Caucasian females (mean age: 69 years; range: 29 to 85 years). RESULTS: Within an individual, the variance in tissue elastic modulus (CV = 18.7%; range: 9 to 41.5%) was five times greater than the variance in TMD (3.6%, range: 1.8 to 5.7%). On average, only 45% of the variance in tissue elastic modulus was explained by TMD. From individual to individual, the proportion of the variance in tissue elastic modulus explained by TMD ranged from 0 to 64%. In 6 of 12 samples, TMD explained less than 30% of the variance in tissue elastic modulus. Results were similar for tissue hardness. CONCLUSION: Tissue mineral density is an incomplete surrogate for tissue elastic modulus. Other material properties need to be accounted for to more fully predict regional variation in tissue elastic modulus.
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Calcificación Fisiológica , Huesos/fisiología , Huesos/ultraestructura , Elasticidad , Femenino , Humanos , Masculino , Microscopía Electrónica de RastreoRESUMEN
The pore-scale behavior of a nonaqueous phase liquid (NAPL) trapped as residual contamination in a porous medium, subject to freeze-thaw cycles, was investigated by X-ray microcomputed tomography. It is shown that freeze-thaw cycles cause significant NAPL remobilization in the direction of the freezing front, due to the rupture and transport of a significant proportion of (supposedly entrapped) larger multipore NAPL ganglia. Significant NAPL remains in place, however, due to substantial ganglion fragmentation into single- and subpore ganglia. The contraction of branched ganglia into more rounded forms, especially near the top surface, is also observed. Three freezing-induced mechanisms are proposed to explain the results. The findings have important implications for NAPL contamination in cold regions, and for the behavior of water-hydrocarbon systems on the Earth and other planets.
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Transición de Fase , Contaminantes Químicos del Agua/química , Monitoreo del Ambiente , Congelación , Permeabilidad , Porosidad , Contaminantes Químicos del Agua/análisis , Microtomografía por Rayos XRESUMEN
In the design of tissue engineering scaffolds, design parameters including pore size, shape and interconnectivity, mechanical properties and transport properties should be optimized to maximize successful inducement of bone ingrowth. In this paper we describe a 3D micro-CT and pore partitioning study to derive pore scale parameters including pore radius distribution, accessible radius, throat radius, and connectivity over the pore space of the tissue engineered constructs. These pore scale descriptors are correlated to bone ingrowth into the scaffolds. Quantitative and visual comparisons show a strong correlation between the local accessible pore radius and bone ingrowth; for well connected samples a cutoff accessible pore radius of approximately 100 microM is observed for ingrowth. The elastic properties of different types of scaffolds are simulated and can be described by standard cellular solids theory: (E/E(0))=(rho/rho(s))(n). Hydraulic conductance and diffusive properties are calculated; results are consistent with the concept of a threshold conductance for bone ingrowth. Simple simulations of local flow velocity and local shear stress show no correlation to in vivo bone ingrowth patterns. These results demonstrate a potential for 3D imaging and analysis to define relevant pore scale morphological and physical properties within scaffolds and to provide evidence for correlations between pore scale descriptors, physical properties and bone ingrowth.
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Cerámica/química , Osteogénesis/fisiología , Ingeniería de Tejidos , Andamios del Tejido/química , Algoritmos , Materiales Biocompatibles/química , Elasticidad , Ensayo de Materiales , Modelos Teóricos , Porosidad , Resistencia al Corte , Propiedades de Superficie , Ingeniería de Tejidos/instrumentación , Ingeniería de Tejidos/métodosRESUMEN
The three-dimensional (3D) structure and architecture of biomaterial scaffolds play a critical role in bone formation as they affect the functionality of the tissue-engineered constructs. Assessment techniques for scaffold design and their efficacy in bone ingrowth studies require an ability to accurately quantify the 3D structure of the scaffold and an ability to visualize the bone regenerative processes within the scaffold structure. In this paper, a 3D micro-CT imaging and analysis study of bone ingrowth into tissue-engineered scaffold materials is described. Seven specimens are studied in this paper; a set of three specimens with a cellular structure, varying pore size and implant material, and a set of four scaffolds with two different scaffold designs investigated at early (4 weeks) and late (12 weeks) explantation times. The difficulty in accurately phase separating the multiple phases within a scaffold undergoing bone regeneration is first highlighted. A sophisticated three-phase segmentation approach is implemented to develop high-quality phase separation with minimal artifacts. A number of structural characteristics and bone ingrowth characteristics of the scaffolds are quantitatively measured on the phase separated images. Porosity, pore size distributions, pore constriction sizes, and pore topology are measured on the original pore phase of the scaffold volumes. The distribution of bone ingrowth into the scaffold pore volume is also measured. For early explanted specimens we observe that bone ingrowth occurs primarily at the periphery of the scaffold with a constant decrease in bone mineralization into the scaffold volume. Pore size distributions defined by both the local pore geometry and by the largest accessible pore show distinctly different behavior. The accessible pore size is strongly correlated to bone ingrowth. In the specimens studied a strong enhancement of bone ingrowth is observed for pore diameters>100 microm. Little difference in bone ingrowth is measured with different scaffold design. This result illustrates the benefits of microtomography for analyzing the 3D structure of scaffolds and the resultant bone ingrowth.
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Materiales Biocompatibles/química , Osteogénesis , Ingeniería de Tejidos/métodos , Tomografía Computarizada por Rayos X/métodos , Óxido de Aluminio/química , Animales , Regeneración Ósea , Huesos/anatomía & histología , Huesos/química , Huesos/fisiología , Hidroxiapatitas/química , Imagenología Tridimensional/métodos , Implantes Experimentales , Porosidad , OvinosRESUMEN
We computationally investigate cross-property correlations linking fluid permeability to conductive properties in sedimentary rock for a number of pore size parameters based on three-dimensional digitized rock images. In particular, we focus on correlations based on the pore volume-to-surface-area ratio (V(p)/S), a critical channel diameter (c) associated with mercury porosimetry measurements, length scales associated with the nuclear magnetic resonance relaxation time T2, as well as the mean survival time (tau). Differences between the length scales are discussed. All these correlations yield good agreement with our simulations, but permeability estimates based on the critical diameter (c) are found to be most reliable.
RESUMEN
This paper illustrates the utility of micro-computed tomography (micro-CT) to study the process of tissue engineered bone growth. A micro-CT facility for imaging and visualising biomaterials in three dimensions (3D) is described. The facility is capable of acquiring 3D images made up of 2000(3) voxels on specimens up to 60mm in extent with resolutions down to 2 microm. This allows the 3D structure of tissue engineered materials to be imaged across three orders of magnitude of detail. The capabilities of micro-CT are demonstrated by imaging the Haversian network within human femoral cortical bone (distal diaphysis) and bone ingrowth into a porous scaffold at varying resolutions. Phase identification combined with 3D visualisation enables one to observe the complex topology of the canalicular system of the cortical bone. Imaging of the tissue engineered bone at a scale of 1cm and resolutions of 10 microm allows visualisation of the complex ingrowth of bone into the polymer scaffold. Further imaging at 2 microm resolution allows observation of bone ultra-structure. These observations illustrate the benefits of tomography over traditional techniques for the characterisation of bone morphology and interconnectivity and performs a complimentary role to current histomorphometric techniques.
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Sustitutos de Huesos , Huesos/química , Fémur/química , Imagenología Tridimensional/métodos , Polímeros/química , Ingeniería de Tejidos/métodos , Tomografía Computarizada por Rayos X/métodos , Densidad Ósea , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Microrradiografía/métodos , Modelos MolecularesRESUMEN
Employing highly efficient algorithms for simulating invasion percolation (IP) with trapping, we obtain precise estimates for the fractal dimensions of the sample-spanning cluster, the backbone, and the minimal path in a variety of two-dimensional lattices. The results indicate that these quantities are nonuniversal and vary with the coordination number Z of the lattices. In particular, while the fractal dimension D(f) of the sample-spanning cluster in lattices with low Z has the generally accepted value of about 1.82, it crosses over to the value of random percolation, D(f) approximately equal to 1.896, if Z is large enough. Since optimal paths in strongly disordered media and minimum spanning trees on random graphs are related to IP, the implication is that these problems do not also possess universal scaling properties.
RESUMEN
We give numerical estimates for the site percolation trapping thresholds for invasion percolation on various three dimensional lattices. We find that in most cases the thresholds for invasion and ordinary percolation coincide. However, for coordination numbers less than five the thresholds diverge. Since most rock networks exhibit coordination numbers less than five the rules for simulating residual saturation in porous rocks must be chosen carefully.