The Production of Porous Hydroxyapatite Scaffolds with Graded Porosity by Sequential Freeze-Casting.
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ABSTRACT:
SUBMITTER: Lee H
PROVIDER: S-EPMC5506897 | biostudies-other | 2017 Mar
REPOSITORIES: biostudies-other
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Project description:As a new strategy for improved urinary drainage, in parallel to the potential for additional functions such as drug release and self-removal, highly porous chitosan stents are manufactured by radial, bi-directional freeze-casting. Inserting the porous stent in to a silicone tube to emulate its placement in the ureter shows that it is shape conforming and remains safely positioned in place, also during flow tests, including those performed in a peristaltic pump. Cyclic compression tests on fully-hydrated porous stents reveal high stent resilience and close to full elastic recovery upon unloading. The drainage performance of the chitosan stent is evaluated, using effective viscosity in addition to volumetric flow and flux; the porous stent's performance is compared to that of the straight portion of a commercial 8 Fr double-J stent which possesses, in its otherwise solid tube wall, regularly spaced holes along its length. Both the porous and the 8 Fr stent show higher effective viscosities, when tested in the silicone tube. The performance of the porous stent improves considerably more (47.5%) than that of the 8 Fr stent (30.6%) upon removal from the tube, illustrating the effectiveness of the radially aligned porosity for drainage. We conclude that the newly-developed porous chitosan ureteral stent merits further in vitro and in vivo assessment of its promise as an alternative and complement to currently available medical devices. STATEMENT OF SIGNIFICANCE: No papers, to date, report on porous ureteral stents, which we propose as a new strategy for improved urinary drainage. The highly porous chitosan stents of our study are manufactured by radial, bi-directional freeze casting. Cyclic compression tests on fully-hydrated porous stents revealed high stent resilience and close to full recovery upon unloading. The drainage performance of the chitosan is evaluated, using effective viscosity in addition to volumetric flow and flux, and compared to that of the straight portion of a commercial 8 Fr double-J stent. The performance of the porous stent improves considerably more (47.5%) than that of the 8 Fr stent (30.6%) upon removal from the tube, illustrating the effectiveness of the radially aligned porosity for drainage. While further studies are required to explore other potential benefits of the porous stent design such as antimicrobial behavior, drug release, and biodegradability, we conclude that the newly-developed porous chitosan ureteral stent has considerable potential as a medical device.
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Project description:Tissues are organized in hierarchical structures comprised of nanoscale, microscale, and macroscale features. Incorporating hierarchical structures into biomaterial scaffolds may enable better resemblance of native tissue structures and improve cell interaction, but it is challenging to produce such scaffolds using a single conventional scaffold production technique. We developed the Freeze-FRESH (FF) technique that combines FRESH 3D printing (3DP) and freeze-casting to produce 3D printed scaffolds with microscale pores in the struts. FF scaffolds were produced by extrusion 3DP using a support bath at room temperature, followed by freezing and lyophilization, then the FF scaffolds were recovered from the bath and crosslinked. The FF scaffolds had a hierarchical pore structure from the combination of microscale pores throughout the scaffold struts and macroscale pores in the printed design, while control scaffolds had only macroscale pores. FF scaffolds frozen at -20 °C and -80 °C had similar pore sizes, due to freezing in the support bath. The -20 °C and -80 °C FF scaffolds had porous struts with 63.55% ± 2.59% and 56.72% ± 13.17% strut porosity, respectively, while control scaffolds had a strut porosity of 3.15% ± 2.20%. The -20 °C and -80 °C FF scaffolds were softer than control scaffolds: they had pore wall stiffness of 0.17 ± 0.06 MPa and 0.23 ± 0.05 MPa, respectively, compared to 1.31 ± 0.39 MPa for the control. The FF scaffolds had increased resilience in bending compared with control. FF scaffolds supported MDA-MB-231 cell growth and had significantly greater cell numbers than control scaffolds. Cells formed clusters on the porous struts of FF scaffolds and had similar morphologies as the freeze cast scaffolds. The FF technique successfully introduced microscale porosity into the 3DP scaffold struts to produce hierarchical pore structures that enhanced MDA-MB-231 growth.
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Project description:Introduction: Simulating hydrophobic-hydrophilic composite face with hierarchical porous and fibrous architectures of bone extracellular matrix (ECM) is a key aspect in bone tissue engineering. This study focused on the fabrication of new three-dimensional (3D) scaffolds containing polytetrafluoroethylene (PTFE), and polyvinyl alcohol (PVA), with and without graphene oxide (GO) nanoparticles using the chemical cross-linking and freeze-drying methods for bone tissue application. The effects of GO on physicochemical features and osteoinduction properties of the scaffolds were evaluated through an in vitro study. Methods: After synthesizing the GO nanoparticles, two types of 3D scaffolds, PTFE/PVA (PP) and PTFE/PVA/GO (PPG), were developed by cross-linking and freeze-drying methods. The physicochemical features of scaffolds were assessed and the interaction of the 3D scaffold types with human adipose mesenchymal stem cells (hADSCs) including attachment, proliferation, and differentiation to osteogenic like cells were investigated. Results: GO nanoparticles were successfully synthesized with no agglomeration. The blending of PTFE as a hydrophobic polymer with PVA polymer and GO nanoparticles (hydrophilic compartments) were successful. Two types of 3D scaffolds had nano topographical structures, good porosities, hydrophilic surfaces, thermal stabilities, good stiffness, as well as supporting the cell attachments, proliferation, and osteogenic differentiation. Notably, GO incorporating scaffolds provided a better milieu for cell behaviors. Conclusion: Novel multiscale porous nanofibrous 3D scaffolds made from PTFE/ PVA polymers with and without GO nanoparticles could be an ideal candidate for bone tissue engineering as a 3D template.
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Project description:3D printed scaffolds can be used, for example, in medical applications for simulating body tissues or for manufacturing prostheses. However, it is difficult to print porous structures of specific porosity and pore size values with fused deposition modelling (FDM) technology. The present paper provides a methodology to design porous structures to be printed. First, a model is defined with some theoretical parallel planes, which are bounded within a geometrical figure, for example a disk. Each plane has randomly distributed points on it. Then, the points are joined with lines. Finally, the lines are given a certain volume and the structure is obtained. The porosity of the structure depends on three geometrical variables: the distance between parallel layers, the number of columns on each layer and the radius of the columns. In order to obtain mathematical models to relate the variables with three responses, the porosity, the mean of pore diameter and the variance of pore diameter of the structures, design of experiments with three-level factorial analysis was used. Finally, multiobjective optimization was carried out by means of the desirability function method. In order to favour fixation of the structures by osseointegration, porosity range between 0.5 and 0.75, mean of pore size between 0.1 and 0.3 mm, and variance of pore size between 0.000 and 0.010 mm² were selected. Results showed that the optimal solution consists of a structure with a height between layers of 0.72 mm, 3.65 points per mm² and a radius of 0.15 mm. It was observed that, given fixed height and radius values, the three responses decrease with the number of points per surface unit. The increase of the radius of the columns implies the decrease of the porosity and of the mean of pore size. The decrease of the height between layers leads to a sharper decrease of both the porosity and the mean of pore size. In order to compare calculated and experimental values, scaffolds were printed in polylactic acid (PLA) with FDM technology. Porosity and pore size were measured with X-ray tomography. Average value of measured porosity was 0.594, while calculated porosity was 0.537. Average value of measured mean of pore size was 0.372 mm, while calculated value was 0.434 mm. Average value of variance of pore size was 0.048 mm², higher than the calculated one of 0.008 mm². In addition, both round and elongated pores were observed in the printed structures. The current methodology allows designing structures with different requirements for porosity and pore size. In addition, it can be applied to other responses. It will be very useful in medical applications such as the simulation of body tissues or the manufacture of prostheses.
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Project description:A method for generating hierarchical scaffolds with graded changes in porosity and/or fiber alignment through solution-masked, vapor-induced welding of electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers is reported. The success of this method relies on the fact that the PLGA nanofibers are swollen and welded more slowly by ethanol when immersed in its aqueous solution relative to direct exposure to its vapor. For a mat composed of random nanofibers, the treatment generates a gradation in porosity (both surface and bulk), with the over-welded region evolving from a highly porous mat into a dense film. If uniaxially aligned nanofibers are involved, however, graded changes are observed in both surface porosity and fiber alignment. When bone marrow stem cells are cultured on such a scaffold, they exhibit highly organized and random morphologies on the regions of uniaxially aligned nanofibers and dense film, respectively, with gradual changes in between. Such a scaffold shows promise in mimicking the connective tissue, such as the tendon-to-bone insertion, that relies on a graded transition in cell morphology from uniaxially aligned to random.
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Project description:poly(l-lactic acid) (PLLA) has been approved for clinical use by the US Food and Drug Administration (FDA); however, their stronger hydrophobicity and relatively fast degradation rate restricted their widespread application. In consideration of the composition of bone, the inorganic-organic composite has a great application prospect in bone tissue engineering. Many inorganic-organic composite scaffolds were prepared by directly mixing the active ingredient, but this method is uncontrolled and will lead to lack of homogeneity in the polymer matrix. Strontium (Sr) is an admirable addition to improve the bioactivity and bone induction of hydroxyapatite (HA). To our knowledge, the application of biomimetic mineralized strontium-doped hydroxyapatite on porous poly(l-lactic acid) (Sr-HA/PLLA) scaffolds for bone defect repair has never been reported till date. Biomimetic mineralized Sr-HA/PLLA porous scaffold was developed in this study. The results indicated that the Sr-HA/PLLA porous scaffold could improve the surface hydrophobicity, reduce the acidic environment of the degradation, and enhance the osteoinductivity; moreover, the ability of protein adsorption and the modulus of compression were increased. The results also clearly showed the effectiveness of the Sr-HA/PLLA porous scaffold in promoting cell adhesion, proliferation, and alkaline phosphatase (ALP) activity. The micro computed tomography (micro-CT) results showed that more new bones were formed by Sr-HA/PLLA porous scaffold treatment. The histological results confirmed the osteoinductivity of the Sr-HA/PLLA porous scaffold. The results suggested that the Sr-HA/PLLA porous scaffold has a good application prospect in bone tissue engineering in the future.The purpose of this study was to promote the bone repair.Surgical operation of rabbits was carried out in this study.The results showed that formation of a large number of new bones by the Sr-HA/PLLA porous scaffold treatment is possible.Biomimetic mineralized Sr-HA/PLLA porous scaffold could effectively promote the restoration of bone defects in vivo.
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