Applications of Alginate-Based Bioinks in 3D Bioprinting.

Three-dimensional (3D) bioprinting is on the cusp of permitting the direct fabrication of artificial living tissue. Multicellular building blocks (bioinks) are dispensed layer by layer and scaled for the target construct. However, only a few materials are able to fulfill the considerable requirements for suitable bioink formulation, a critical component of efficient 3D bioprinting. Alginate, a naturally occurring polysaccharide, is clearly the most commonly employed material in current bioinks. Here, we discuss the benefits and disadvantages of the use of alginate in 3D bioprinting by summarizing the most recent studies that used alginate for printing vascular tissue, bone and cartilage. In addition, other breakthroughs in the use of alginate in bioprinting are discussed, including strategies to improve its structural and degradation characteristics. In this review, we organize the available literature in order to inspire and accelerate novel alginate-based bioink formulations with enhanced properties for future applications in basic research, drug screening and regenerative medicine.no funding source acknowledge

The viscoelastic response of electrospun poly(vinyl alcohol) mats.

Native biological tissues are viscoelastic materials that undergo time-dependent loading in vivo. It is therefore crucial to ensure that biomedical materials have a suitable viscoelastic response for a given application. In this study, the viscoelastic properties of electrospun poly(vinyl alcohol) are investigated using tensile load relaxation testing. A five-parameter generalised Maxwell constitutive model is found to characterise the experimental response. The effect of polymer concentration and electrospinning voltage on model parameters is investigated in detail. The stiffness coefficients for the relaxation process appear to be dependent on the electrospinning conditions used whereas the time constants remain relatively unchanged. It is also observed that the stiffness parameters are linearly correlated with the equilibrium modulus, indicating that a single underlying material property dictates the relaxation moduli. Lastly, it is found that the viscoelastic model parameters are not predicted by the fibre diameter. These results provide an important understanding in designing electrospun mats with desired time-dependent properties

Nanofibrous hydrogel composites as mechanically robust tissue engineering scaffolds.

Hydrogels closely resemble the extracellular matrix (ECM) and can support cell proliferation while new tissue is formed, making them materials of choice as tissue engineering scaffolds. However, their sometimes-poor mechanical properties can hinder their application. The addition of meshes of nanofibers embedded in their matrix forms a composite that draws from the advantages of both components. Given that these materials are still in the early stages of development, there is a lack of uniformity across methods for characterizing their mechanical properties. Here, we propose a simple metric to enable comparisons between materials. The fibrous constituent improves the mechanical properties of the hydrogel, while the biocompatibility and functionality of the gels are maintained or even improved.The authors acknowledge the support of the EPSRC through a doctoral training award (ALB) and via the Nano Science and Technology Doctoral Training Centre (NanoDTC), EP/G037221/1 (GSO).This is the accepted manuscript. The final version is available from http://www.cell.com/trends/biotechnology/references/S0167-7799%2814%2900181-4

Size effects in indentation of hydrated biological tissues

Fluid flow in biological tissues is important in both mechanical and biological contexts. Given the hierarchical nature of tissues, there are varying length scales at which time-dependent mechanical behavior due to fluid flow may be exhibited. Here, spherical nanoindentation and microindentation testings are used for the characterization of length scale effects in the mechanical response of hydrated tissues. Although elastic properties were consistent across length scales, there was a substantial difference between the time-dependent mechanical responses for large and small contact radii in the same tissue specimens. This difference was far more obvious when poroelastic analysis was used instead of viscoelastic analysis. Overall, indentation testing is a fast and robust technique for characterizing the hierarchical structure of biological materials from nanometer to micrometer length scales and is capable of making quantitative material property measurements to do with fluid flo

Multi-scale mechanical response of freeze-dried collagen scaffolds for tissue engineering applications.

Tissue engineering has grown in the past two decades as a promising solution to unresolved clinical problems such as osteoarthritis. The mechanical response of tissue engineering scaffolds is one of the factors determining their use in applications such as cartilage and bone repair. The relationship between the structural and intrinsic mechanical properties of the scaffolds was the object of this study, with the ultimate aim of understanding the stiffness of the substrate that adhered cells experience, and its link to the bulk mechanical properties. Freeze-dried type I collagen porous scaffolds made with varying slurry concentrations and pore sizes were tested in a viscoelastic framework by macroindentation. Membranes made up of stacks of pore walls were indented using colloidal probe atomic force microscopy. It was found that the bulk scaffold mechanical response varied with collagen concentration in the slurry consistent with previous studies on these materials. Hydration of the scaffolds resulted in a more compliant response, yet lesser viscoelastic relaxation. Indentation of the membranes suggested that the material making up the pore walls remains unchanged between conditions, so that the stiffness of the scaffolds at the scale of seeded cells is unchanged; rather, it is suggested that thicker pore walls or more of these result in the increased moduli for the greater slurry concentration conditions.The authors are grateful to the Nano Doctoral Training Centre (NanoDTC), University of Cambridge, and the EPSRC who supported this work through the EP/G037221/1 grant.This is the final published version. It originally appeared at http://www.sciencedirect.com/science/article/pii/S1751616114003397#

Three-dimensional modeling of human placental terminal villi.

INTRODUCTION: Placental transport is the main factor affecting the health and development of the fetus. Due to the placenta's geometrical and mathematical complexity, the structure-function relations of placental terminal villi have not been successfully modeled. Hence, a novel modeling approach is proposed. METHODS: Computational models of four different specimens were generated from the three-dimensional reconstruction of confocal laser scanning microscopic image stacks. To evaluate the capabilities of the proposed methodology, stationary oxygen diffusion transport was calculated in the terminal villus volumes. RESULTS: The reconstructions automatically provided the spatial arrangement of the fetal capillaries inside the terminal villi. The surface and volume ratios between the fetal capillaries and the villus were also calculated, and the effects of model parameters on the placental diffusive capacity were assessed by parametric analysis. DISCUSSION: The potential of three-dimensional reconstructions combined with finite element analysis as a research tool for the human placenta was tested. The methodology herein could serve in the future as a simulation platform for complicated in vivo and in vitro scenarios.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.placenta.2016.05.00

Kontribusi USAhatani Ternak Kambing dalam Meningkatkan Pendapatan Petani (Studi Kasus di Desa Batungsel, Kecamatan Pupuan, Kabupaten Tabanan)

The aims of this study were to analyze: (1) goat farm contribution to the farmer\u27s income, (2) minimum farm scale for providing benefit, and (3) financial feasibility of the goat farm. This study was conducted in the Batungsel Village, Pupuan District, Tabanan Regency. Interview used questioner to farmers is done to collect data. Income analysis, BEP (Break Event Point), Profit Rate, and R/C ratio, was used in this study. The results of this study showed that: net income of the farmer from goat farm was Rp. 6,375,000. Profit rate 66.93% and R/C ratio of 1.67 showed that the goat farm was feasible financially. Break Event Point can be attain on Rp. 6,284,393 of the revenue or 8 goat of production. Income from goat farm give the largest contribution to total farmer income. This study indicated that the goat farm can be used as a solution to reducing poverty rate in the villages

Size effects in indentation of hydrated biological tissues

Fluid flow in biological tissues is important in both mechanical and biological contexts. Given the hierarchical nature of tissues, there are varying length scales at which time-dependent mechanical behavior due to fluid flow may be exhibited. Here, spherical nanoindentation and microindentation testings are used for the characterization of length scale effects in the mechanical response of hydrated tissues. Although elastic properties were consistent across length scales, there was a substantial difference between the time-dependent mechanical responses for large and small contact radii in the same tissue specimens. This difference was far more obvious when poroelastic analysis was used instead of viscoelastic analysis. Overall, indentation testing is a fast and robust technique for characterizing the hierarchical structure of biological materials from nanometer to micrometer length scales and is capable of making quantitative material property measurements to do with fluid flow

Viscoelastic and poroelastic mechanical characterization of hydrated gels

Measurement of the mechanical behavior of hydrated gels is challenging due to a relatively small elastic modulus and dominant time-dependence compared with traditional engineering materials. Here polyacrylamide gel materials are examined using different techniques (indentation, unconfined compression, dynamic mechanical analysis) at different length-scales and considering both viscoelastic and poroelastic mechanical frameworks. Elastic modulus values were similar for nanoindentation and microindentation, but both indentation techniques overestimated elastic modulus values compared to homogeneous loading techniques. Hydraulic and intrinsic permeability values from microindentation tests, deconvoluted using a poroelastic finite element model, were consistent with literature values for gels of the same composition. Although elastic modulus values were comparable for viscoelastic and poroelastic analyses, time-dependent behavior was length-scale dependent, supporting the use of a poroelastic, instead of a viscoelastic, framework for future Studies of gel mechanical behavior under indentation