Current tissue regenerative strategies rely mainly on tissue repair by transplantation of the synthetic/natural implants. However, limitations of the existing strategies have increased the demand for tissue engineering approaches. Appropriate cell source, effective cell modification, and proper supportive matrices are three bases of tissue engineering. Selection of appropriate methods for cell stimulation, scaffold synthesis, and tissue transplantation play a definitive role in successful tissue engineering. Although the variety of the players are available, but proper combination and functional synergism determine the practical efficacy. Hence, in this review, a comprehensive view of tissue engineering and its different aspects are investigated.

Tissue engineering; strategies, tissues, and biomaterials.

The complex relationship between the hydrodynamic environment and surrounding tissues directly impacts on the design and production of clinically useful grafts and implants. Tissue engineers have generally seen bioreactors as 'black boxes' within which tissue engineering constructs (TECs) are cultured. It is accepted that a more detailed description of fluid mechanics and nutrient transport within process equipment can be achieved by using computational fluid dynamics (CFD) technology. This review discusses applications of CFD for tissue engineering-related bioreactors -- fluid flow processes have direct implications on cellular responses such as attachment, migration and proliferation. We conclude that CFD should be seen as an invaluable tool for analyzing and visualizing the impact of fluidic forces and stresses on cells and TECs.

Computational fluid dynamics for improved bioreactor design and 3D culture

The main challenge in tissue engineering consists in understanding and controlling the growth process of in vitro cultured neotissues toward obtaining functional tissues. Computational models can provide crucial information on appropriate bioreactor and scaffold design but also on the bioprocess environment and culture conditions. In this study, the development of a 3D model using the level set method to capture the growth of a microporous neotissue domain in a dynamic culture environment (perfusion bioreactor) was pursued. In our model, neotissue growth velocity was influenced by scaffold geometry as well as by flow- induced shear stresses. The neotissue was modeled as a homogenous porous medium with a given permeability, and the Brinkman equation was used to calculate the flow profile in both neotissue and void space. Neotissue growth was modeled until the scaffold void volume was filled, thus capturing already established experimental observations, in particular the differences between scaffold filling under different flow regimes. This tool is envisaged as a scaffold shape and bioprocess optimization tool with predictive capacities. It will allow controlling fluid flow during long-term culture, whereby neotissue growth alters flow patterns, in order to provide shear stress profiles and magnitudes across the whole scaffold volume influencing, in turn, the neotissue growth.

/pdf/coupling-curvature-dependent-and-shear-stress-stimulated-2l20lo0rs4.pdf

Coupling curvature-dependent and shear stress-stimulated neotissue growth in dynamic bioreactor cultures: a 3D computational model of a complete scaffold

Application of computational fluid dynamics in tissue engineering.

A novel cardiac scaffold comprised of decellularized porcine heart matrix was investigated for use as a biodegradable patch with a potential for surgical reconstruction of the right ventricular outflow tract. Powdered heart matrix solution was blended with chitosan and lyophilized to form three-dimensional scaffolds. For this investigation, we examined the influence of different blending ratios of heart matrix to chitosan on porosity and mechanical properties, then gene expression and electrophysiological function of invading neonatal rat ventricular myocytes (NRVM) compared to type-A gelatin/chitosan composite scaffolds. Heart matrix/chitosan-blended hydrogels (1.6 mg/mL heart matrix) had similar porosity (109±34 μm), and elastic modulus (13.2±4.0 kPa) as previously published gelatin/chitosan scaffolds. Heart matrix/chitosan hydrogels maintained>80% viability and had higher NRVM retention (∼1000 cells/mm2) than gelatin/chitosan scaffolds. There was a significant increase in α-myosin heavy chain and conne...

/pdf/use-of-myocardial-matrix-in-a-chitosan-based-full-thickness-2l5d458m25.pdf

Use of Myocardial Matrix in a Chitosan-Based Full-Thickness Heart Patch

The objective of this study was to investigate a bioreactor suitable for human bladder regeneration. Simulations were performed using the computational fluid dynamic tools. The thickness of the bladder scaffold was 3 mm, similar to the human bladder, and overall hold-up volume within the spherical shape scaffold was 755 ml. All simulations were performed using (i) Brinkman equation on porous regions using the properties of 1% chitosan–1% gelatin structures, (ii) Michaelis–Menten type rate law nutrient consumption for smooth muscle cells (SMCs) and (iii) Mackie–Meares relationship for determining effective diffusivities. Steady state simulations were performed using flow rates from 0.5 to 5 ml/min. Two different inlet shapes: (i) straight entry at the centre (Design 1) and (ii) entry with an expansion (Design 2) were simulated to evaluate shear stress distribution. Also, mimicking bladder shape of two inlets (Design 3) was tested. Design 2 provided the uniform shear stress at the inlet and nutrient distrib...

Computational simulation modelling of bioreactor configurations for regenerating human bladder

In this study, transport characteristics in flow-through and parallel-flow bioreactors used in tissue engineering were simulated using computational fluid dynamics. To study nutrient distribution and consumption by smooth muscle cells colonizing the 100 mm diameter and 2-mm thick scaffold, effective diffusivity of glucose was experimentally determined using a two-chambered setup. Three different concentrations of chitosan-gelatin scaffolds were prepared by freezing at -80°C followed by lyophilization. Experiments were performed in both bioreactors to measure pressure drop at different flow rates. At low flow rates, experimental results were in agreement with the simulation results for both bioreactors. However, increase in flow rate beyond 5 mL/min in flow-through bioreactor showed channeling at the circumference resulting in lower pressure drop relative to simulation results. The Peclet number inside the scaffold indicated nutrient distribution within the flow-through bioreactor to be convection-dependent, whereas the parallel-flow bioreactor was diffusion-dependent. Three alternative design modifications to the parallel-flow were made by (i) introducing an additional inlet and an outlet, (ii) changing channel position, and (iii) changing the hold-up volume. Simulation studies were performed to assess the effect of scaffold thickness, cell densities, and permeability. These new designs improved nutrient distribution for 2 mm scaffolds; however, parallel-flow configuration was found to be unsuitable for scaffolds more than 4-mm thick, especially at low porosities as tissues regenerate. Furthermore, operable flow rate in flow-through bioreactors is constrained by the mechanical strength of the scaffold. In summary, this study showed limitations and differences between flow-through and parallel-flow bioreactors used in tissue engineering.

Dynamics of diffusivity and pressure drop in flow‐through and parallel‐flow bioreactors during tissue regeneration

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Computational simulation modelling of bioreactor configurations for regenerating human bladder

Dynamics of diffusivity and pressure drop in flow‐through and parallel‐flow bioreactors during tissue regeneration