State of Art on Solvent Casting Particulate Leaching Method for Orthopedic ScaffoldsFabrication

The design and fabrication of tissue engineering scaffolds is a highly complex process. In order to provide a proper architecture for cells to grow, proliferate, and differentiate to form tissues, scaffolds have to be made with suitable properties. However, the limited structural designs and conventional fabrication techniques severely cripple the improvement of scaffold properties. To overcome these limitations, many researchers have recently adopted computational methods combined with 3D printing techniques as a new approach for scaffold design and fabrication. This approach allows scaffolds to be designed and fabricated with highly complex microstructures and good control and accuracy. Previous works have also shown this approach to be a very useful tool to predict the scaffold properties and to optimize the scaffold designs with a great reduction of experimental iterations. As this approach combining computational methods and 3D printing techniques for scaffold design and fabrication has many advantages over the conventional trial-and-error based approach, it is imperative to provide a state-of-the-art review on the topic. To this end, this article reviews the various applications of computational methods in scaffold design and simulation; it also briefly reviews the application of 3D printing techniques to fabricate the computationally designed scaffolds. Finally, the limitations and future trends of this approach are discussed. Overall, this review will enable readers to understand the benefits of using computational methods coupled with 3D printing to design and fabricate scaffolds, and thus help researchers to improve and optimize the scaffold properties for future tissue engineering research. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1329-1351, 2019.

A review on the use of computational methods to characterize, design, and optimize tissue engineering scaffolds, with a potential in 3D printing fabrication.

In vitro experiments of a biomaterial's degradability rarely predict its in vivo behaviour. It is now shown that tracking the hydrolytic and enzymatic erosion of model materials by non-invasive fluorescence imaging allows the prediction of in vivo erosion from in vitro data. The approach should enable rapid screening of erodable biomaterials.

In vivo and in vitro tracking of erosion in biodegradable materials using non-invasive fluorescence imaging

Design of 3D printed scaffolds for bone tissue engineering: A review

Hydrogel-based three-dimensional (3D) bioprinting has been illustrated as promising to fabricate tissue scaffolds for regenerative medicine. Notably, bioprinting of hydrated and soft 3D hydrogel scaffolds with desired structural properties has not been fully achieved so far. Moreover, due to the limitations of current imaging techniques, assessment of bioprinted hydrogel scaffolds is still challenging, yet still essential for scaffold design, fabrication, and longitudinal studies. This paper presents our study on the bioprinting of hydrogel scaffolds and on the development of a novel noninvasive imaging method, based on synchrotron propagation-based imaging with computed tomography (SR-PBI-CT), to study the structural properties of hydrogel scaffolds and their responses to environmental stimuli both in situ and in vivo. Hydrogel scaffolds designed with varying structural patterns were successfully bioprinted through rigorous printing process regulations and then imaged by SR-PBI-CT within physiological environments. Subjective to controllable compressive loadings, the structural responses of scaffolds were visualized and characterized in terms of the structural deformation caused by the compressive loadings. Hydrogel scaffolds were later implanted in rats as nerve conduits for SR-PBI-CT imaging, and the obtained images illustrated their high phase contrast and were further processed for the 3D structure reconstruction and quantitative characterization. Our results show that the scaffold design and printing conditions play important roles in the printed scaffold structure and mechanical properties. More importantly, our obtained images from SR-PBI-CT allow us to visualize the details of hydrogel 3D structures with high imaging resolution. It demonstrates unique capability of this imaging technique for noninvasive, in situ characterization of 3D hydrogel structures pre- and post-implantation in diverse physiological milieus. The established imaging platform can therefore be utilized as a robust, high-precision tool for the design and longitudinal studies of hydrogel scaffold in tissue engineering.

Noninvasive Three-Dimensional In Situ and In Vivo Characterization of Bioprinted Hydrogel Scaffolds Using the X-ray Propagation-Based Imaging Technique.

In tissue engineering, the cell and scaffold approach has shown promise as a treatment to regenerate diseased and/or damaged tissue. In this treatment, an artificial construct (scaffold) is seeded with cells, which organize and proliferate into new tissue. The scaffold itself biodegrades with time, leaving behind only newly formed tissue. The degradation qualities of the scaffold are critical during the treatment period, since the change in the mechanical properties of the scaffold with time can influence cell behavior. To observe in time the scaffold's mechanical properties, a straightforward method is to deform the scaffold and then characterize scaffold deflection accordingly. However, experimentally observing the scaffold deflection is challenging. This paper presents a novel study on characterization of mechanical properties of scaffolds by phase contrast imaging and finite element modeling, which specifically includes scaffold fabrication, scaffold imaging, image analysis, and finite elements (FEs) modeling of the scaffold mechanical properties. The innovation of the work rests on the use of in-line phase contrast X-ray imaging at 20 KeV to characterize tissue scaffold deformation caused by ultrasound radiation forces and the use of the Fourier transform to identify movement. Once deformation has been determined experimentally, it is then compared with the predictions given by the forward solution of a finite element model. A consideration of the number of separate loading conditions necessary to uniquely identify the material properties of transversely isotropic and fully orthotropic scaffolds is also presented, along with the use of an FE as a form of regularization.

Characterization of Mechanical Properties of Tissue Scaffolds by Phase Contrast Imaging and Finite Element Modeling.

The fracture properties of cortical bone are directly coupled to its complex hierarchical structure. The limited availability of bone material from many anatomic locations creates challenges for assessing the effect of bone heterogeneity and anisotropy on fracture properties. The small punch technique was employed to examine the fracture behavior of cortical bone in terms of area under the curve values obtained from load-load point displacement behavior. Fracture toughness of cortical bone was also determined in terms of J-toughness values obtained using a compact tension (CT) test. Area under the curve values obtained from the small punch test were correlated with the J-toughness values of cortical bone. The effects of bone density and compositional parameters on area under the curve and Jtoughness values were also analyzed using linear and multiple regression analysis. Area under the curve and J-toughness values are strongly and positively correlated. Bone density and %mineral content are positively correlated with both area under the curve and J-toughness values. The multiple regression analysis outcomes support these results. Overall, the findings support the hypothesis that area under the curve values obtained from small punch tests can be used to assess the fracture behavior of cortical bone.

Assessment of Elastic-Plastic Fracture Behavior of Cortical Bone Using a Small Punch Testing Technique.

Bone is a complex material that exhibits an amount of plasticity before bone fracture takes place, where the non-linear relationship between stress and strain is of importance to understanding the mechanism behind the fracture. This brief presents our study on the examination of the stress-stain relationship of bovine femoral cortical bone and the relationship representation by employing the Ramberg-Osgood (R-O) equation. Samples were taken and prepared from different locations (upper, middle and lower) of bone diaphysis and were then subjected to the uniaxial tensile tests under longitudinal and transverse loading conditions, respectively. The stress-strain curves obtained from tests were analyzed via linear regression analysis based on the R-O equation. Our results illustrated that the R-O equation is appropriate to describe the non-linear stress-strain behavior of cortical bone, while the values of equation parameters vary with the sample locations (upper, middle and lower) and loading conditions (longitudinal and transverse).

Studies on ramberg-osgood equation parameters of cortical bone.

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Papers

Characterization of Mechanical Properties of Tissue Scaffolds by Phase Contrast Imaging and Finite Element Modeling.

Assessment of Elastic-Plastic Fracture Behavior of Cortical Bone Using a Small Punch Testing Technique.

Studies on ramberg-osgood equation parameters of cortical bone.