Porous Scaffolds For Tissue Engineering Research Articles

Silk-Based 3D Porous Scaffolds for Tissue Engineering.

Silk fibroin, extracted from the silk of the Bombyx mori silkworm, stands out as a biomaterial due to its nontoxic nature, excellent biocompatibility, and adjustable biodegradability. Porous scaffolds, a type of biomaterial, are crucial for creating an optimal microenvironment that supports cell adhesion and proliferation, thereby playing an essential role in tissue remodeling and repair. Therefore, this review focuses on 3D porous silk fibroin-based scaffolds, first summarizing their preparation methods and then detailing their regenerative effects on bone, cartilage, tendon, vascular, neural, skin, hepatic, and tracheal epithelial tissue engineering in recent years.

Meniscal repair with additive manufacture of bioresorbable polymer: From physicochemical characterization to implantation of 3D printed poly (L-co-D, L lactide-co-trimethylene carbonate) with autologous stem cells in rabbits.

Three-dimensional (3D) structures are actually the state-of-the-art technique to create porous scaffolds for tissue engineering. Since regeneration in cartilage tissue is limited due to intrinsic cellular properties this study aims to develop and characterize three-dimensional porous scaffolds of poly (L-co-D, L lactide-co-trimethylene carbonate), PLDLA-TMC, obtained by 3D fiber deposition technique. The PLDLA-TMC terpolymer scaffolds (70:30), were obtained and characterized by scanning electron microscopy, gel permeation chromatography, differential scanning calorimetry, thermal gravimetric analysis, compression mechanical testing and study on in vitro degradation, which showed its amorphous characteristics, cylindrical geometry, and interconnected pores. The in vitro degradation study showed significant loss of mechanical properties compatible with a decrease in molar mass, accompanied by changes in morphology. The histocompatibility association of mesenchymal stem cells from rabbit's bone marrow, and PLDLA-TMC scaffolds, were evaluated in the meniscus regeneration, proving the potential of cell culture at in vivo tissue regeneration. Nine New Zealand rabbits underwent total medial meniscectomy, yielding three treatments: implantation of the seeded PLDLA-TMC scaffold, implantation of the unseeded PLDLA-TMC and negative control (defect without any implant). After 24weeks, the results revealed the presence of fibrocartilage in the animals treated with polymer. However, the regeneration obtained with the seeded PLDLA-TMC scaffolds with mesenchymal stem cells had become intimal to mature fibrocartilaginous tissue of normal meniscus both macroscopically and histologically. This study demonstrated the effectiveness of the PLDLA-TMC scaffold in meniscus regeneration and the potential of mesenchymal stem cells in tissue engineering, without the use of growth factors. It is concluded that bioresorbable polymers represent a promising alternative for tissue regeneration.

Adaptable test bench for ASTM-compliant permeability measurement of porous scaffolds for tissue engineering

Intrinsic permeability describes the ability of a porous medium to be penetrated by a fluid. Considering porous scaffolds for tissue engineering (TE) applications, this macroscopic variable can strongly influence the transport of oxygen and nutrients, the cell seeding process, and the transmission of fluid forces to the cells, playing a crucial role in determining scaffold efficacy. Thus, accurately measuring the permeability of porous scaffolds could represent an essential step in their optimization process. In literature, several methods have been proposed to characterize scaffold permeability. Most of the currently adopted approaches to assess permeability limit their applicability to specific scaffold structures, hampering protocols standardization, and ultimately leading to incomparable results among different laboratories. The content of novelty of this study is in the proposal of an adaptable test bench and in defining a specific testing protocol, compliant with the ASTM International F2952-22 guidelines, for reliable and repeatable measurements of the intrinsic permeability of TE porous scaffolds. The developed permeability test bench (PTB) exploits the pump-based method, and it is composed of a modular permeability chamber integrated within a closed-loop hydraulic circuit, which includes a peristaltic pump and pressure sensors, recirculating demineralized water. A specific testing protocol was defined for characterizing the pressure drop associated with the scaffold under test, while minimizing the effects of uncertainty sources. To assess the operational capabilities and performance of the proposed test bench, permeability measurements were conducted on PLA scaffolds with regular (PS) and random (RS) micro-architecture and on commercial bovine bone matrix-derived scaffolds (CS) for bone TE. To validate the proposed approach, the scaffolds were as well characterized using an alternative test bench (ATB) based on acoustic measurements, implementing a blind randomized testing procedure. The consistency of the permeability values measured using both the test benches demonstrated the reliability of the proposed approach. A further validation of the PTB’s measurement reliability was provided by the agreement between the measured permeability values of the PS scaffolds and the theory-based predicted permeability value. Once validated the proposed PTB, the performed measurements allowed the investigation of the scaffolds’ transport properties. Samples with the same structure (guaranteed by the fused-deposition modeling technique) were characterized by similar permeability values, and CS and RS scaffolds showed permeability values in agreement with the values reported in the literature for bovine trabecular bone. In conclusion, the developed PTB and the proposed testing protocol allow the characterization of the intrinsic permeability of porous scaffolds of different types and dimensions under controlled flow regimes, representing a powerful tool in view of providing a reliable and repeatable framework for characterizing and optimizing scaffolds for TE applications.

Recent Developments in Engineered Magnesium Scaffolds for Bone Tissue Engineering.

Significant attention has been drawn in recent years to develop porous scaffolds for tissue engineering. In general, porous scaffolds are used for non-load bearing applications. However, various metallic scaffolds have been investigated extensively for hard tissue repair due to their favorable mechanical and biological properties. Stainless steel (316L) and titanium (Ti) alloys are the most commonly used material for metallic scaffolds. Although stainless steel and Ti alloys are employed as scaffold materials, it might result in complications such as stress shielding, local irritation, interference with radiography, etc. related to the permanent implants. To address the above-mentioned complications, degradable metallic scaffolds have emerged as a next generation material. Among the all metallic degradable scaffold materials, magnesium (Mg) based material has gained significant attention owing to its advantageous mechanical properties and excellent biocompatibility in a physiological environment. Therefore, Mg based materials can be projected as load bearing degradable scaffolds, which can provide structural support toward the defected hard tissue during the healing period. Moreover, advanced manufacturing techniques such as solvent cast 3D printing, negative salt pattern molding, laser perforation, and surface modifications can make Mg based scaffolds promising for hard tissue repair. In this article, we focus on the advanced fabrication techniques which can tune the porosity of the degradable Mg based scaffold favorably and improve its biocompatibility.

Development of Boron-Containing PVA-Based Cryogels with Controllable Boron Releasing Rate and Altered Influence on Osteoblasts

Cryogel formation is an effective approach to produce porous scaffolds for tissue engineering. In this study, cryogelation was performed to produce boron-containing scaffolds for bone tissue engineering. A combination of the synthetic polymer, poly(vinyl alcohol) (PVA), and the natural polymers, chitosan and starch, was used to formulate the cryogels. Boron was used with a dual purpose: as an additive to alter gelation properties, and to exploit its bioactive effect since boron has been found to be involved in several metabolic pathways, including the promotion of bone growth. This project designs a fabrication protocol enabling the competition of both physical and chemical cross-linking reactions in the cryogels using different molecular weight PVA and borax content (boron source). Using a high ratio of high-molecular-weight PVA resulted in the cryogels exhibiting greater mechanical properties, a lower degradation rate (0.6-1.7% vs. 18-20%) and a higher borax content release (4.98 vs. 1.85, 1.08 nanomole) in contrast to their counterparts with low-molecular-weight PVA. The bioactive impacts of the released borax on cellular behaviour were investigated using MG63 cells seeded into the cryogel scaffolds. It was revealed that the borax-containing scaffolds and their extracts induced MG63 cell migration and the formation of nodule-like aggregates, whilst cryogel scaffolds without borax did not. Moreover, the degradation products of the scaffolds were analysed through the quantification of boron release by the curcumin assay. The impact on cellular response in a scratch assay confirmed that borax released by the scaffold into media (~0.4 mg/mL) induced bone cell migration, proliferation and aggregation. This study demonstrated that boron-containing three-dimensional PVA/starch-chitosan scaffolds can potentially be used within bone tissue engineering applications.

Travelling-Wave and Asymptotic Analysis of a Multiphase Moving Boundary Model for Engineered Tissue Growth

We derive a multiphase, moving boundary model to represent the development of tissue in vitro in a porous tissue engineering scaffold. We consider a cell, extra-cellular liquid and a rigid scaffold phase, and adopt Darcy’s law to relate the velocity of the cell and liquid phases to their respective pressures. Cell–cell and cell–scaffold interactions which can drive cellular motion are accounted for by utilising relevant constitutive assumptions for the pressure in the cell phase. We reduce the model to a nonlinear reaction–diffusion equation for the cell phase, coupled to a moving boundary condition for the tissue edge, the diffusivity being dependent on the cell and scaffold volume fractions, cell and liquid viscosities and parameters that relate to cellular motion. Numerical simulations reveal that the reduced model admits three regimes for the evolution of the tissue edge at large time: linear, logarithmic and stationary. Employing travelling-wave and asymptotic analysis, we characterise these regimes in terms of parameters related to cellular production and motion. The results of our investigation allow us to suggest optimal values for the governing parameters, so as to stimulate tissue growth in an engineering scaffold.

Freezing-modulated-crosslinking: A crosslinking approach for 3D cryoprinting

3D Bioprinting is a popular method of fabricating scaffolds for tissue engineering. While soft bioinks such as alginate are useful for reproducing the softest tissues of the human body, it remains difficult to 3D print objects out of bioinks that cannot support their own weight. 3D cryoprinting is a promising method of printing objects out of soft bioinks and creating highly porous scaffolds for tissue engineering. However, crosslinking the frozen objects before they thaw and collapse remains a challenge. Here we investigate a process which we name “freezing-modulated-crosslinking” for crosslinking frozen objects produced by 3D cryoprinting. During freezing-modulated-crosslinking, frozen objects are thawed in a crosslinker bath at a controlled melting rate, so that crosslinking occurs layer by layer and the object can maintain its printed shape. First, we examine the process with a mathematical model to determine the important thermal parameters. Second, we validate our results experimentally by printing a variety of multi-layer alginate objects. By systematically examining this crosslinking approach, we expand the options for 3D cryoprinting. 3D cryoprinted alginate scaffolds can be seeded with cells for use in 3D cell culture or for tissue regeneration.

Fabrication of a stepwise degradable hybrid bioscaffold based on the natural and partially denatured collagen

As a major component of extracellular matrixes (ECMs), collagen is an attractive biomaterial to fabricate porous scaffold for tissue engineering due to their similarity to the in vivo static microenvironment. However, the collagen-based porous scaffolds were difficult to mimic the dynamically remolded porous structure of ECM during the cell proliferation and tissue development, and always have poor mechanical property and not easy to handle. Here, natural collagen and partially denatured collagen was used to prepare the stepwise degradable hybrid bioscaffold with suitable mechanical property and dynamically remolded inner porous structure, which is desirable for the applications of tissue engineering. The collagen-based microporous scaffold was first prepared and used as physical support, then, the mechanical strength of which was reinforced by the import of the partially denatured collagen to give the hybrid bioscaffold. The fabrication conditions of the hybrid scaffolds were optimized, of which the thermal stability, mechanical property, and swelling property was explored. The stepwise enzymatic degradation process and the corresponding porous structure variation of the hybrid scaffold was confirmed by SEM and cell culture assays.

A Modular Three-Dimensional Bioprinter for Printing Porous Scaffolds for Tissue Engineering

Abstract Three-dimensional (3D) bioprinting is a fabrication method with many biomedical applications, particularly within tissue engineering. The use of freezing during 3D bioprinting, aka “3D cryoprinting,” can be utilized to create micopores within tissue-engineered scaffolds to enhance cell proliferation. When used with alginate bio-inks, this type of 3D cryoprinting requires three steps: 3D printing, crosslinking, and freezing. This study investigated the influence of crosslinking order and cooling rate on the microstructure and mechanical properties of sodium alginate scaffolds. We designed and built a novel modular 3D printer in order to study the effects of these steps separately and to address many of the manufacturing issues associated with 3D cryoprinting. With the modular 3D printer, 3D printing, crosslinking, and freezing were conducted on separate modules yet remain part of a continuous manufacturing process. Crosslinking before the freezing step produced highly interconnected and directional pores, which are ideal for promoting cell growth. By controlling the cooling rate, it was possible to produce pores with diameters from a range of 5 μm to 40 μm. Tensile and firmness testing found that the use of freezing does not decrease the tensile strength of the printed objects, though there was a significant loss in firmness for strands with larger pores.

One-Pot Preparation of Hydrophilic Polylactide Porous Scaffolds by Using Safe Solvent and Choline Taurinate Ionic Liquid.

Polylactides (PLAs) are a class of polymers that are very appealing in biomedical applications due to their degradability in nontoxic products, tunable structural, and mechanical properties. However, they have some drawbacks related to their high hydrophobicity, lack of functional groups able to graft bioactive molecules, and solubility in unsafe solvents. To circumvent these shortcomings, porous scaffolds for tissue engineering were prepared by vigorously mixing a solution of isotactic and atactic PLA in nontoxic ethyl acetate at 70 °C with a water solution of choline taurinate. The partial aminolysis of the polymer ester bonds by taurine –NH2 brought about the formation of PLA oligomers with surfactant activity that stabilized the water-in-oil emulsion. Upon drying, a negligible shrinking occurred, and mechanically stable porous scaffolds were obtained. By varying the polymer composition and choline taurinate concentration, it was possible to modulate the pore dimensions (30–50 µm) and mechanical properties (Young’s moduli: 1–6 MPa) of the samples. Furthermore, the grafted choline taurinate made the surface of the PLA films hydrophilic, as observed by contact angle measurements (advancing contact angle: 76°; receding contact angle: 40°–13°). The preparation method was very simple because it was based on a one-pot mild reaction that did not require an additional purification step, as all the employed chemicals were nontoxic.

Computational method and program for generating a porous scaffold based on implicit surfaces

Background and objectiveThe triply periodic minimal surface (TPMS) method effectively mimics the porous scaffold for tissue engineering with continuous topology, pore interconnections, and high surface area to volume ratio. However, the process to generate a three-dimensional (3D) mesh of porous structure from the mimicked organs is complicated for biologists and sometimes requires various software. Herein, we present the standalone program called "Scaffolder" for generating the porous topology from the user-input 3D model to the open-source community. MethodsThe 3D mesh of a porous scaffold was used by the proposed method and dual-marching cubes algorithm. Afterward, the mesh was sliced into the contours to examine pore sizes by Feret diameter and Gilbert–Johnson–Keerthi distance. The relationships between the program parameters (i.e., grid size, angular frequency, and iso-level) and scaffold properties (i.e., pore size, porosity, and surface area ratio) were investigated. ResultsThe developed program can generate and evaluate a porous scaffold. The median (IQR) absolute errors in grid size of 200, 300, 400, and 500 divisions were 1.92 (0.35-3.80), 1.00 (0.18-2.22), 0.53 (0-1.37), and 0.24 (0-0.74), respectively. Spearman's correlation showed the impact of angular frequency and iso-level on the pore size, porosity, and surface area of the generated scaffold (p<0.05). ConclusionsThis study enables researchers to rapidly design the 3D mesh of porous scaffold design, evaluate scaffold properties, and customize the implicit function for various applications, especially in tissue engineering and computational structural analysis.

The effect of diameter of fibre on formation of hydrogen bonds and mechanical properties of 3D-printed PCL.

Fused Deposition Modelling (FDM) technique has been widely utilized in fabrication of 3D porous scaffolds for tissue engineering (TE) applications. Surprisingly, although there are many publications devoted to the architectural features of the 3D scaffolds fabricated by the FDM, none of them give us evident information about the impact of the diameter of the fibres on material properties. Therefore, the aim of this study was to investigate, for the first time, the effect of the diameter of 3D-printed PCL fibres on variations in their microstructure and resulting mechanical behaviour. The fibres made of poly(ε-caprolactone) (PCL) were extruded through commonly used types of nozzles (inner diameter ranging from 0.18 mm to 1.07 mm) by means of FDM technique. Static tensile test and atomic force microscopy working in force spectroscopy mode revealed strong decrease in the Young's modulus and yield strength with increasing fibre diameter in the investigated range. To explain this phenomenon, we conducted differential scanning calorimetry, wide-angle X-ray-scattering, Fourier-transform infrared spectroscopy, infrared and polarized light microscopy imaging. The obtained results clearly showed that the most prominent effect on the obtained microstructures and mechanical properties had different cooling and shear rates during fabrication process causing changes in supramolecular interactions of PCL. The observed fibre size-dependent formation of hydrogen bonds affected the crystalline structure and its stability. Summarising, this study clearly demonstrates that the diameter of 3D-printed fibres has a strong effect on obtained microstructure and mechanical properties, therefore should be taken into consideration during design of the 3D TE scaffolds.

A multiphase multiscale model for nutrient-limited tissue growth, Part II: a simplified description

In this paper, we revisit our previous work in which we derive an effective macroscale description suitable to describe the growth of biological tissue within a porous tissue-engineering scaffold. The underlying tissue dynamics is described as a multiphase mixture, thereby naturally accommodating features such as interstitial growth and active cell motion. Via a linearization of the underlying multiphase model (whose nonlinearity poses a significant challenge for such analyses), we obtain, by means of multiple-scale homogenization, a simplified macroscale model that nevertheless retains explicit dependence on both the microscale scaffold structure and the tissue dynamics, via so-called unit-cell problems that provide permeability tensors to parameterize the macroscale description. In our previous work, the cell problems retain macroscale dependence, posing significant challenges for computational implementation of the eventual macroscopic model; here, we obtain a decoupled system whereby the quasi-steady cell problems may be solved separately from the macroscale description. Moreover, we indicate how the formulation is influenced by a set of alternative microscale boundary conditions.&#x0D; &#x0D; doi:10.1017/S1446181119000130

Fabrication of bimodal open-porous poly (butylene succinate)/cellulose nanocrystals composite scaffolds for tissue engineering application

The design of porous tissue engineering scaffold with multiscale open-pore architecture (i.e., bimodal structure) promotes cell attachment and growth, which facilitates nutrient and oxygen diffusion. In this study, a porous poly (butylene succinate) (PBS)/cellulose nanocrystals (CNCs) composite scaffold with a well-defined controllable bimodal open-pore interconnected structure was successfully fabricated. The bimodal open-porous scaffold architecture was designed by synergistic control of temperature variation and a two-step depressurization in a supercritical carbon dioxide (Sc-CO2) foaming process. The microstructure and properties of the bimodal open-porous PBS/CNCs scaffold, such as morphology, open porosity, hydrophilic and degradation performance, and mechanical compression properties, were analyzed. In the experiments, the scaffold with unimodal pore structure was used for comparison. The results showed that the bimodal open-porous PBS5 scaffold displayed a well-defined bimodal open-pore structure composed of large pore (~68.9 μm in diameter) and small pore (~11.0 μm in diameter), with a high open porosity (~95.2%). In addition, the scaffolds exhibited good mechanical compressive properties (compressive strength of 2.76 MPa at 50% strain), hydrophilicity (water contact angle of 71.7 °C) and in vitro degradation rate. Moreover, in vitro biocompatibility was determined with NIH-3T3 fibroblast cells using MTT assay and live/dead cell viability assay. Results indicated that the obtained bimodal open-porous scaffolds had a good biocompatibility and the viability of cells grown on the scaffolds reached up to 98% after 7th day of culture. Therefore, our work provides new insights into the use of biodegradable polymeric composite scaffolds with bimodal open-pore structure and balanced properties in tissue engineering.

Permeability and fluid flow-induced wall shear stress in bone scaffolds with TPMS and lattice architectures: A CFD analysis

Abstract Fluid flow dynamics within porous scaffolds for tissue engineering play a critical role in the transport of fundamental materials to the cells and in controlling the biocompatibility of the scaffold. Properties such as permeability and fluid flow-induced wall shear stress characterize the biological behavior of the scaffolds. Bioactivity depends on the diffusion of oxygen and other nutritious elements through the porous medium and fluid flow-induced shear stress is known as the dominant mechanical stimulant of cell differentiation and proliferation within the scaffolds. In this study, eight different bone scaffold models with a constant porosity of 80% were designed computationally using the TPMS and lattice-based structures. We investigated the fluid flow within the scaffolds using CFD analysis. The results of the work showed that scaffold architecture has a significant impact on the permeability and that scaffold permeability can vary up to three times depending on the architecture. The scaffolds with the minimal variation in their channel size exhibited the highest permeability. We investigated the distribution statistics of wall shear stress on the walls of the scaffolds and showed that a correlation between the architecture of the scaffolds and the distribution statistics of wall shear stress did not exist. The outcomings of this work can be promising in designing better scaffolds in tissue engineering from a biological point of view.

A MULTIPHASE MULTISCALE MODEL FOR NUTRIENT-LIMITED TISSUE GROWTH, PART II: A SIMPLIFIED DESCRIPTION

In this paper, we revisit our previous work in which we derive an effective macroscale description suitable to describe the growth of biological tissue within a porous tissue-engineering scaffold. The underlying tissue dynamics is described as a multiphase mixture, thereby naturally accommodating features such as interstitial growth and active cell motion. Via a linearization of the underlying multiphase model (whose nonlinearity poses a significant challenge for such analyses), we obtain, by means of multiple-scale homogenization, a simplified macroscale model that nevertheless retains explicit dependence on both the microscale scaffold structure and the tissue dynamics, via so-called unit-cell problems that provide permeability tensors to parameterize the macroscale description. In our previous work, the cell problems retain macroscale dependence, posing significant challenges for computational implementation of the eventual macroscopic model; here, we obtain a decoupled system whereby the quasi-steady cell problems may be solved separately from the macroscale description. Moreover, we indicate how the formulation is influenced by a set of alternative microscale boundary conditions.

Structural mechanics of 3D-printed poly(lactic acid) scaffolds with tetragonal, hexagonal and wheel-like designs

While various porous scaffolds have been developed, the focused study about which structure leads to better mechanics is rare. In this study, we designed porous scaffolds with tetragonal, hexagonal and wheel-like structures under a given porosity, and fabricated corresponding poly(lactic acid) (PLA) scaffolds with three-dimensional printing. High-resolution micro-computed tomography was carried out to calculate their experimental porosity and confirm their high interconnectivity. The theoretical and experimental compressive properties in the longitudinal direction were characterized by finite element analysis method and electromechanical universal testing system, respectively. Thereinto, the scaffold with the tetragonal structure exhibited higher mechanical strength both theoretically and experimentally. Creep and stress relaxation behaviors of the scaffolds revealed that the tetragonal scaffold had less significant viscoelasticity. Immersion dynamic mechanical analysis was performed to test their cycle-loading fatigue behaviors in the simulated body fluid at 37 °C; the tetragonal scaffold exhibited the latest fatigue beginning point at 4400 cycles, which indicated a better anti-fatigue performance; the hexagonal and wheel-like ones exhibited the middle and earliest fatigue beginning points at 3200 and 2500 cycles, respectively. What is more, cytocompatibility and histocompatibility of the scaffolds with all of the structures were confirmed by cell counting kit-8 assay in vitro and three-month subcutaneous implantation in rats in vivo. Hence, the key property difference of the three examined structures comes from their mechanics; the tetragonal structure exhibited better mechanics in the longitudinal direction examined in this study, which could be taken into consideration in design of a porous scaffold for tissue engineering and regeneration.

Developments of 3D polycaprolactone/beta-tricalcium phosphate/collagen scaffolds for hard tissue engineering

3D bioprinting provides an innovative strategy to fabricate a new composite scaffold material consisted in a porous and rough structure with using polycaprolactone (PCL), beta-tricalcium phosphate (β-TCP), and collagen as a building block for tissue engineering. We investigated the optimization of the scaffold properties based on the β-TCP concentration using 3D bioprinting method. Computer-aided drawing was applied in order to digitally design the scaffolds while instead of solid filaments, materials were prepared as a blend solution and controlled evaporation of the solvent during the bioprinting was enabled the proper solidification of the scaffolds, and they were successfully produced with well-defined porous structure. This work demonstrated the feasibility of complex PCL/β-TCP/collagen scaffolds as an alternative in the 3D bioprinting engineering to the fabrication of porous scaffolds for tissue engineering.

Curvature- and fluid-stress-driven tissue growth in a tissue-engineering scaffold pore

Cell proliferation within a fluid-filled porous tissue-engineering scaffold depends on a sensitive choice of pore geometry and flow rates: regions of high curvature encourage cell proliferation, while a critical flow rate is required to promote growth for certain cell types. When the flow rate is too slow, the nutrient supply is limited; when it is too fast, cells may be damaged by the high fluid shear stress. As a result, determining appropriate tissue-engineering-construct geometries and operating regimes poses a significant challenge that cannot be addressed by experimentation alone. In this paper, we present a mathematical theory for the fluid flow within a pore of a tissue-engineering scaffold, which is coupled to the growth of cells on the pore walls. We exploit the slenderness of a pore that is typical in such a scenario, to derive a reduced model that enables a comprehensive analysis of the system to be performed. We derive analytical solutions in a particular case of a nearly piecewise constant growth law and compare these with numerical solutions of the reduced model. Qualitative comparisons of tissue morphologies predicted by our model, with those observed experimentally, are also made. We demonstrate how the simplified system may be used to make predictions on the design of a tissue-engineering scaffold and the appropriate operating regime that ensures a desired level of tissue growth.

Fabrication of highly interconnected porous poly(ɛ-caprolactone) scaffolds with supercritical CO2 foaming and polymer leaching

Highly interconnected porous poly(ɛ-caprolactone) (PCL) scaffolds combined with supercritical carbon dioxide (CO2) foaming and a polymer leaching process were fabricated by blending PCL with water-soluble poly(ethyleneoxide) (PEO) as a sacrificial material. The effects of foaming conditions and the phase morphology of blend on foaming behavior and pore morphology were investigated. Rheological results and phase morphology indicated that the PCL and PEO were immiscible. For both spherical droplets and co-continuous phase morphologies of PCL/PEO blend, batch foaming experimental results indicated that increasing CO2 saturation time and foaming pressure led to significant decreases in pore size, but increasing temperature led to opposite results. The incorporation of PEO not only facilitated the foaming of PCL by increasing its viscosity, but it also improved the porosity and interconnectivity of the post-leached PCL scaffolds. The porosity improved by up to 93.5%, and the open pore content increased by up to 90.9% for the PCL50 blend (50% PCL by weight). The leaching process had more contribution on the open pore content for PCL/PEO porous scaffolds with co-continuous phase morphologies than for the spherical droplet structures due to different cell-opening mechanisms. The results gathered in this study may provide a theoretical basis and data to support research into porous scaffolds for tissue engineering.