Fabrication of a porous wall and higher interconnectivity scaffold comprising gelatin/chitosan via combination of salt-leaching and lyophilization methods

A novel gelatin/chitosan scaffold with higher porosity and interconnectivity was designed through salt-leaching/lyophilization (SLL) method. The properties of the fabricated scaffolds were compared with conventional scaffolds, which are obtained by thermally induced phase-separation (TIPS) method. The scaffolds made by phase-separation method have high tensile strength, but suffer from less channel interconnectivity, pore uniformity and also low surface porosity. The microstructure, porosity, phosphate-buffered saline (PBS) solution absorption and tensile strength of the prepared scaffolds by SLL method were studied. In this work, SLL as a two-step technique is introduced for creating porosity to improve both channel interconnectivity and pore uniformity for water-soluble polymers in comparison with the TIPS method. The SLL technique includes two mechanisms: the first, leaching of mixed sodium chloride crystals and particles created during recrystallization of the dissolved NaCl and the second, phase separation during lyophilization at the pore walls. These two steps in porosity formation lead to special pore morphology, which is more suitable for cell culturing because of higher interconnectivity and rich surface porosity in comparison with the phase-separated scaffolds. The prepared scaffolds, using this technique with different salt/polymer ratios and salt crystal size, have 91?C97% porosity and 94?C190???m mean pore size with tensile strength of 72?C215?kPa and PBS solution absorption between 12.4 and 19 times dry weight. The pore size of scaffolds prepared using the SLL method could be adjusted independently of polymer solution concentration. These scaffolds have a great potential in skin tissue engineering application.     

An investigation into the influence of electrospinning parameters on the diameter and alignment of poly(hydroxybutyrate‐co‐hydroxyvalerate) fibers

Electrospinning is an effective technology for the fabrication of ultrafine fibers, which can be the basic component of a tissue engineering scaffold. In tissue engineering, because cells seeded on fibrous scaffolds with varying fiber diameters and morphologies exhibit different responses, it is critical to control these characteristics of electrospun fibers. The diameter and morphology of electrospun fibers can be influenced by many processing parameters (e.g., electrospinning voltage, needle inner diameter, solution feeding rate, rotational speed of the fiber‐collecting cylinder, and working distance) and solution properties (polymer solution concentration and conductivity). In this study, a factorial design approach was used to systematically investigate the degree of influence of each of these parameters on fiber diameter, degree of fiber alignment, and their possible synergetic effects, using a natural biodegradable polymer, poly(hydroxybutyrate‐co‐hydroxyvalerate), for the electrospinning experiments. It was found that the solution concentration invoked the highest main effect on fiber diameter, whereas both rotational speed of the fiber‐collecting cylinder and addition of a conductivity‐enhancing salt could significantly affect the degree of fiber alignment. By carefully controlling the electrospinning parameters and solution properties, fibrous scaffolds of desired characteristics could be made to meet the requirements of different tissue engineering applications. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

A parametric study on the processing parameters and properties of a porous poly(DL‐lactide‐co‐glycolide) acid 85/15 bioscaffolds

This study presents a comprehensive parametric study on the effects of processing parameters on the poly(DL‐lactide‐co‐glycolide) acid (PLGA) 85/15 scaffold's physical properties. Porous PLGA 85/15 scaffolds were prepared using a gas foaming/salt leaching technique. The processing parameters under examination for the gas foaming/salt leaching method included: gas saturation pressure (SP), gas saturation time, and NaCl/polymer mass ratio (NaCl/PMR). The physical properties considered in this study were the scaffold density, the scaffold porosity, and the average pore size of the scaffold. Young's moduli in compression, as well as the pore density (PD) inside the scaffold, were also studied. The results demonstrated optimum correlations of processing parameters are required to produce a scaffold with a high level of interconnectivity. In general, all scaffolds yielded by this experiment exhibited a porosity more than 90%, a relative density ranging from 0.0534 to 0.149 g/cm³, a PD ranging from 1.51 × 10⁶ to 6.72 × 10⁶ pores/cm³, and a compressive modulus ranging from 0.07 to 0.84 MPa. It was determined that the NaCl/PMR was the parameter that had the most significant effect on the physical properties of the scaffold. The average pore size was affected slightly by the SP only, and it was observed that the pore size was equivalent to the size of the NaCl particles used to make the scaffold. POLYM. ENG. SCI., 2009. © 2009 Society of Plastics Engineers     

Interconnectivity and permeability of supercritical fluid-foamed scaffolds and the effect of their structural properties on cell distribution

This study aims to investigate interconnectivity and permeability of scCO₂-foamed scaffolds and the influence of structural scaffold properties on cell distribution. Supercritical fluid technology was utilized to fabricated scaffolds from 37 kDa, 53 kDa and 109 kDa PLGA (85:15). Pore size, pore size distribution and porosity were quantified by MicroCT, and window sizes were measured using SEM. A novel interconnectivity algorithm allowed the quantification of scaffold interconnectivity in three space dimensions. To determine the permeability of porous materials direct perfusion experiments were performed, where a known flow rate was applied to measure the pressure differential across the scaffolds. The permeability was calculated using Darcy's law. Largest pore sizes, porosities, interconnectivities and permeabilities were obtained for scaffolds fabricated from 37 kDa PLGA. These scaffolds showed a heterogeneous pore structure and distribution, whereas homogeneous pore structure, smallest pore sizes, porosities, interconnectivities and permeabilities were observed for scaffolds fabricated from 109 kDa PLGA. The distribution of 3T3 fibroblasts through scCO₂-foamed scaffolds was investigated by MicroCT and MTT staining. Cells were further visualized by fluorescent imaging. Uniform cell distribution was observed on scaffolds fabricated from 109 kDa PLGA and an average of 10% of the total scaffold volume was covered with cells that had adhered onto them.     

3D Composite scaffolds using strontium containing bioactive glasses

In this study, it was aimed to fabricate and characterize three-dimensional composite scaffolds derived from Sr-doped bioactive glass for bone tissue engineering applications. The scaffolds were fabricated by using polymer foam replication technique and coated with gelatin to be able to improve the properties of them. The porous scaffolds were successfully synthesized using optimized process parameters. Both coated and uncoated scaffolds favored precipitation of calcium phosphate layer when they were soaked in simulated body fluid (SBF). Gelatin coating improved the mechanical properties of the scaffold and also it did not change the bioactive behavior of the scaffold. It was observed that there was a good pore interconnectivity maintained in the scaffold microstructure. Results indicated that scaffolds can deliver controlled doses of strontium toward the SBF medium. That is the determinant for bone tissue regeneration, as far as strontium is known to positively act on bone remodeling.     

Preparation of enhanced three-dimensional porous chitosan scaffolds by acetylation and aqueous extraction

We have devised a method to prepare a 3-dimensional (3D) porous acetylated chitosan scaffold for use as a cell adhesion matrix in tissue engineering applications. The scaffold was prepared by molding a mixture of chitosan and gelatin (as porogen), then removing the uncomplexed porogen by aqueous extraction from the freeze-dried material prior to acetylation. The extent of chitosan acetylation according to the reaction time was observed by X-ray diffraction (XRD) analysis. The differences between the aqueous-extracted and control phase-separated chitosan scaffolds in terms of pore morphology and interconnectivity were examined by scanning electron microscopy (SEM), enzymatic degradation, and surface roughness tests. The fibroblast cell line NIH-3T3 was used to test relative cell affinities for the acetylated versus untreated (control) chitosan scaffolds. The acetylated 3D porous scaffolds showed high interconnectivity and improved biocompatibility properties. Thus, these scaffolds may be very useful for a variety of tissue engineering applications.     

Facile preparation and cytocompatibility of poly(lactic acid)/poly(3‐hydroxybutyrate‐co‐4‐hydroxybutyrate) hybrid fibrous scaffolds

A fibrous scaffold is required to provide three‐dimensional (3D) cell growth microenvironments and appropriate synergistic cell guidance cues. In this study, porous scaffolds with different mass ratio of poly(lactic acid) to poly(3‐hydroxybutyrate‐co‐4‐hydroxybutyrate) (P(3HB‐co‐4HB)) for tissue engineering were prepared by a modified particle leaching method. The effect of the addition of P(3HB‐co‐4HB) on microstructural morphology, compression property, swelling behavior, and enzymatic degradation of hybrid scaffolds was systematically investigated. The results indicated that this method was simple but efficient to prepare highly interconnected biomimetic 3D hybrid scaffolds (PP50/50 and PP33/67) with fibrous pore walls. The cytocompatibility of hybrid scaffolds was evaluated by in vitro culture of mesenchymal stem cells. The cell‐cultured hybrid scaffolds presented a complete 3D porous structure, thus allowing cell proliferation on the surface and infiltration into the inner part of scaffolds. The obtained hybrid scaffolds with pore size ranging from 200 to 450 µm, over 90% porosity, adjustable biodegradability, and water‐uptake capability will be promising for cartilage tissue engineering applications. POLYM. ENG. SCI., 54:2902–2910, 2014. © 2014 Society of Plastics Engineers     

Fabrication of polylactic acid/polyethylene glycol (PLA/PEG) porous scaffold by supercritical CO2 foaming and particle leaching

PLA/PEG/NaCl blends were melt‐blended followed by gas foaming and particle leaching process to fabricate porous scaffold with high porosity and interconnectivity. A home‐made triple‐screw compounding extruder was used to intensify the mixability and dispersion of NaCl and PEG in the PLA matrix. Supercritical carbon dioxide was used as physical blowing agent for the microcellular foaming process. Sodium chloride (NaCl) was used as the porogen to further improve the porosity of PLA scaffold. This study investigated the effects of PEG and NaCl on the structure and properties of the PLA‐based blend, as well as the porosity, pore size, interconnectivity, and hydrophilicity of porous scaffolds. It was found that the incorporation of PEG and NaCl significantly improved the crystallization rate and reduced viscoelasticity of PLA. Moreover, scaffolds obtained from PLA/PEG/NaCl blends had an interconnected bimodal porous structure with the open‐pore content about 86% and the highest porosity of 80%. And the presence of PEG in PLA/NaCl composite improved the extraction ability of NaCl particles during leaching process, which resulted in a well‐interconnected structure. The biocompatibility of the porous scaffolds fabricated was verified by culturing fibroblast cells for 10 days. POLYM. ENG. SCI., 55:1339–1348, 2015. © 2015 Society of Plastics Engineers     

Technology of electrostatic spinning for the production of polyurethane tissue engineering scaffolds

Electrostatic spinning was investigated as an alternative to electrospinning to establish the potential of the technique for the production of a range of microfibrous polyurethane scaffolds with a variety of structures and properties related to the fabrication conditions. Tecoflex^® SG‐80A polyurethane was spun, systematically altering the spinning parameters, and the resulting scaffolds were characterised using scanning electron microscopy. Inter‐fibre separation was significantly affected by flow rate, spray distance and grid and mandrel voltages; fibre diameter by flow rate and mandrel voltage; void fraction by flow rate; fibre orientation by traverse speed and mandrel speed; and thickness by flow rate. Thus, scaffold (three‐dimensional) architecture may be controlled through manipulation of the electric fields and the fibre deposition (spinning parameters of flow rate and grid and mandrel voltages); and by spray movement and direction (spinning parameters of relative spray height, spray distance, traverse speed and mandrel speed). There were significant differences between the internal and external scaffold surfaces, due in part to the manner in which the surface of the mandrels was prepared. We conclude that the process may be used to produce a range of polyurethane scaffolds for use in many tissue engineering applications. Copyright © 2007 Society of Chemical Industry     

Fabrication of PLA/PEG/MWCNT electrospun nanofibrous scaffolds for anticancer drug delivery

In the present study, polylactic acid (PLA)/polyethylene glycol (PEG)/multiwalled carbon nanotube (MWCNT) electrospun nanofibrous scaffolds were prepared via electrospinning process and their applications for the anticancer drug delivery system were investigated. A response surface methodology based on Box–Behnken design (BBD) was used to evaluate the effect of key parameters of electrospinning process including solution concentration, feeding rate, tip–collector distance (TCD) and applied voltage on the morphology of PLA/PEG/MWCNT nanofibrous scaffolds. In optimum conditions (concentration of 8.15%, feeding rate of 0.2 mL/h, voltage of 18.50 kV and TCD of 13.0 cm), the minimum experimental fiber diameter was found to be 225 nm which was in good agreement with the predicted value by the BBD analysis (228 nm). In vitro drug release study of doxorubicin (DOX)‐loaded nanofibrous scaffolds, higher drug content induced an extended release of drug. Also, drug release rate was not dependent on drug/polymer ratio in different electrospun nanofibrous formulations. The equation of M_t = c₀ + kt^0.5was used to describe the kinetic data of DOX release from electrospun nanofibers. The cell viability of DOX‐loaded nanofibrous scaffolds was evaluated using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, a tetrazole assay on lung cancer A549 cell lines. We propose that DOX‐incorporated PLA/PEG/MWCNT nanofibrous scaffold could be used as a superior candidate for antitumor drug delivery. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41286.     

Formation of porous PLGA scaffolds by a combining method of thermally induced phase separation and porogen leaching

A novel method for the fabrication of porous poly(L -lactide-co-glycolide) (PLGA) scaffolds by combining thermally induced phase separation and porogen leaching is presented in this article. Big pores with about 75–400 μm diameters in the obtained scaffolds were generated by the porogen, sucrose particles, while small pores with diameters less than 20 μm induced via phase separation. Extraction of the solvent, chloroform by ethanol at cool temperatures could reduce the scaffold toxicity. Effects of PLGA concentration, freezing temperature, volume fraction of porogen, and introduction of β-tricalcium phosphate (β-TCP) on morphology, porosity, and compressive properties of the scaffolds were systematically discussed. Results showed that the size of small pores decreased by decreasing the polymer concentration and reducing the freezing temperature, whereas the interconnectivity of the scaffolds was improved by increasing the porogen fraction. The compressive modulus and strength were significantly lowered by increasing the scaffold porosity, that is, by increasing porogen fraction, or decreasing the polymer concentration, or reducing the freezing temperature. Addition of β-TCP into the scaffolds did not influence the compressive modulus significantly but tended to decrease the compressive strength. The obtained scaffolds with diverse pore sizes would be potentially used in bone tissue engineering. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Biofabrication of Gelatin Tissue Scaffolds with Uniform Pore Size via Microbubble Assembly

The control of pore size and uniform porosity remains as an important challenge in gelatin scaffolds. The precise control in building blocks of tissue scaffolds without any additional porogen is possible with costly equipment and techniques, though some pre‐requirements for polymeric material, such as photo‐polymerizability or sintering ability, may be needed prior to construction. Herein, a method for the fabrication of gelatin scaffolds with homogenous porosity using simple T‐junction microfluidics is described. The size of the microbubbles is precisely controlled with 5% deviation from the average. Porous gelatin scaffolds are obtained by building‐up the monodispersed microbubbles in dilute cross‐linker solutions. The effect of cross‐linker density on pore diameter is also investigated. After cross‐linking, pore size of the resultant five scaffold groups are precisely controlled as 135 ± 11, 193 ± 11, 216 ± 9, 231 ± 5, and 250 ± 12 µm. Porosity ratios above 65% are achieved in every sample group. According to the cell culture experiments, structures support high cell adhesion, viability, and migration through the porous network via interconnectivity. This study offers a practical and economical approach for the preparation of porous gelatin scaffolds with homogenous porosity which can be utilized in diverse tissue engineering applications.     

Composite scaffolds for cartilage tissue engineering based on natural polymers of bacterial origin,thermoplastic poly(3‐hydroxybutyrate) and micro‐fibrillated bacterial cellulose

Cartilage tissue engineering is an emerging therapeutic strategy that aims to regenerate damaged cartilage caused by disease, trauma, ageing or developmental disorder. Since cartilage lacks regenerative capabilities, it is essential to develop approaches that deliver the appropriate cells, biomaterials and signalling factors to the defect site. Materials and fabrication technologies are therefore critically important for cartilage tissue engineering in designing temporary, artificial extracellular matrices (scaffolds), which support 3D cartilage formation. Hence, this work aimed to investigate the use of poly(3‐hydroxybutyrate)/microfibrillated bacterial cellulose (P(3HB)/MFC) composites as 3D‐scaffolds for potential application in cartilage tissue engineering. The compression moulding/particulate leaching technique employed in the study resulted in good dispersion and a strong adhesion between the MFC and the P(3HB) matrix. Furthermore, the composite scaffold produced displayed better mechanical properties than the neat P(3HB) scaffold. On addition of 10, 20, 30 and 40 wt% MFC to the P(3HB) matrix, the compressive modulus was found to have increased by 35%, 37%, 64% and 124%, while the compression yield strength increased by 95%, 97%, 98% and 102% respectively with respect to neat P(3HB). Both cell attachment and proliferation were found to be optimal on the polymer‐based 3D composite scaffolds produced, indicating a non‐toxic and highly compatible surface for the adhesion and proliferation of mouse chondrogenic ATDC5 cells. The large pores sizes (60 ‐ 83 µm) in the 3D scaffold allowed infiltration and migration of ATDC5 cells deep into the porous network of the scaffold material. Overall this work confirmed the potential of P(3HB)/MFC composites as novel materials in cartilage tissue engineering. © 2016 Society of Chemical Industry     

Fabrication and characterization of porous β-tricalcium phosphate scaffolds coated with alginate

All porous materials have a common limitation which is lack of strength due to the porosity. In this study, two different methods have been used to produce porous β-tricalcium phosphate (β-TCP) scaffolds: liquid-nitrogen freeze casting and a combination of the direct-foaming and sacrificial-template methods. Among these two methods, porous β-TCP scaffolds with acceptable pore size and compressive strength and defined pore-channel interconnectivity were successfully fabricated by the combined direct-foaming and sacrificial-template method. The average pore size of the scaffolds was in the range of 100–150 µm and the porosity was around 70%. Coating with 4 wt% alginate on porous β-TCP scaffolds led to higher compressive strength and low porosity. In order to make a chemical link between the β-TCP scaffolds and the alginate coating, silane coupling agent was used. Treated β-TCP scaffold showed improvements in compressive strength of up to 38% compared to the pure β-TCP scaffold and 11% compared to coated β-TCP scaffold.     

Macroporous Bioglass-derived scaffolds for bone tissue regeneration

Since it was introduced at the end of the ‘60s, the 45S5 Bioglass^® has played a fundamental role among the materials for orthopedic applications because of its ability to build a stable bond with the surrounding bone. The recent development of bone tissue engineering has led the interest of many scientists in the design of Bioglass^®-based scaffolds, i.e. porous systems able to drive and foster the bone tissue regrowth. Among the available techniques to realize scaffolds, the polymer burning out method, which employs organic particles as pore generating agents in a ceramic matrix, combines versatility and low cost. In spite of the advantages of the polymer burning out method, this technique has been rarely applied to 45S5 Bioglass^® and a systematic feasibility study has not been carried out on this issue yet. In order to fill this gap, in the present contribution the polymer burning out method was employed to design macroporous scaffolds based on 45S5 Bioglass^®. Different amounts of organic phase were used to obtain samples with different porosity. The samples were characterized from a microstructural point of view, in order to evaluate the pore morphology, dimension and degree of interconnectivity. Such findings proved that a proper setting of the processing parameters made it possible to achieve very high porosity values, among the best ones obtained in the literature with the same technique, together with an appreciable mechanical behaviour, according to compression tests. Finally, the scaffolds bioactivity was assessed by means of in vitro tests in a simulated body fluid (SBF) solution. Moreover, in the view of a potential application for bone tissue engineering, a preliminary biological evaluation of the obtained scaffolds to sustain cell proliferation was carried out.     

A novel foam-like silane modified alumina scaffold coated with nano-hydroxyapatite–poly(ε-caprolactone fumarate) composite layer

Although alumina scaffolds with biodegradable polymer coating can overcome the limitations of conventional ceramic bone substitutes, the bioactivity potential of these scaffolds needs to be enhanced. In this study, the macroporous alumina scaffolds with the defined pore-channel interconnectivity were successfully prepared by the foam replication method. The average pore size of the scaffolds was in the range 200–900 μm with around 82% porosity. The average Young's modulus of alumina scaffolds was 2.8 GPa. Coating of nano-hydroxyapatite (nano-HA) in poly(ε-caprolactone fumarate) (PCLF) as a carrier on the surface of alumina scaffold was performed. The nano-HA powder was synthesized successfully by the sol–gel method. The crystallite and particle sizes of HA powders were in nano range and confirmed by the Scherrer equation from X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The PCLF was synthesized and characterized by fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). In order to make a chemical link between the alumina scaffolds and the coating, a silane coupling agent was used. The results showed that using of 1 g Methacryloxypropyl trimethoxysilane in 100 g solvent is sufficient for making a thin interface layer between the scaffold and the polymer. The coating process was performed by immersion of scaffolds in the solutions with different percents of nano-HA. The morphology and chemical structure of the coated scaffolds were investigated by SEM and FTIR. SEM images demonstrated that the scaffolds were constituted of interconnected and homogeneously distributed pores. Also, HA distribution and agglomerates on the surface of scaffolds were enhanced by increasing the nano-HA percent in the coating solutions.     

Assessment of cell proliferation in knitting scaffolds with respect to pore‐size heterogeneity,surface wettability,and surface roughness

In this study, various types of poly(ε‐caprolactone) (PCL) knitting scaffolds were fabricated and analyzed to assess the cell‐culturing characteristics of knitting scaffolds with respect to pore‐size heterogeneity, surface wettability, and surface roughness. First, control knitting scaffolds were fabricated using 150‐µm‐diameter PCL monofilaments. Using chloroform and NaOH, PCL knitting scaffolds with varying roughness, pore‐size heterogeneity, and surface wettability were fabricated. Cell‐culture assessments were performed on these six types of PCL knitting scaffolds. Saos‐2 cells were used for cell assessments and cultured for 14 days on each scaffold. Consequently, heterogeneous pore‐size distribution and high surface wettability were found to enhance cell proliferation in knitting scaffolds. In addition, for highly hydrophobic knitting scaffolds exhibiting water contact angles greater than 110 degrees, smaller surface roughness was found to enhance cell proliferation. According to this study, in the case of knitting scaffold, NaOH‐treated knitting scaffold, without any control for the pore‐size homogenization, could be a candidate as the optimal knitting scaffold. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42566.     

Effect of Polymer Concentration on Autoclaved Cryogel Properties

Biomaterial sterilization is a prerequisite prior to patient's use, especially for scaffold implantation or injection. Various sterilization processes are mandated by the Food and Drug Administration including high‐pressure steam sterilization. Although high‐pressure steam or autoclave sterilization eliminates pathogens, it often leads to irreversible damages on soft materials such as hydrogels. In the current study, the impact of autoclave sterilization on cryogels made from several naturally‐derived polymeric precursors (alginate, hyaluronic acid, and gelatin) is analyzed. Specifically, the impact of polymer concentration on the structural and physical properties of autoclaved cryogels such as mechanics, swelling ratio, pore interconnectivity, and shape‐memory features is studied. The results demonstrate that at a given optimal polymer concentration, unique for each biopolymer investigated, autoclave sterilization does not substantially alter the microarchitectural or physical characteristics of cryogels, including their syringe injectability signature. In summary, when formulated under optimized polymer concentrations, autoclavable cryogels hold great potential for several biomedical applications, as they can be easily translated into clinical practice to benefit public health.     

Toughening of bio-ceramics scaffolds by polymer coating

In this work, polycaprolactone-coated alumina scaffolds were produced and characterized to validate the concept of polymer–ceramic composites with increased fracture resistance. Alumina scaffolds were sintered using a foam replication technique. An open-porous structure was achieved with ∼70% porosity and 150 μm mean pore size. The polymer coating was obtained by infiltrating the scaffold with either a polycaprolactone solution or a polycaprolactone nanodispersion. The latter was obtained by an emulsion–diffusion technique. Dynamical Young modulus measurements and four-point bending tests were conducted to evaluate the mechanical properties of the composites. It was found that their elastic behaviour is controlled on the first order by the ceramic scaffold, while the fracture energy mainly depends on the polymer phase. A 10–20 vol.% addition of polycaprolactone to alumina scaffolds led to a 7- to 13-fold increase of the apparent fracture energy. SEM observations showed that toughening is due to crack bridging by polymer fibrils.     

A facile preparation of highly interconnected macroporous poly(d,l-lactic acid-co-glycolic acid) (PLGA) scaffolds by liquid-liquid phase separation of a PLGA-dioxane-water ternary system

Regular and highly interconnected macroporous scaffolds ranging in size from 50 to 150 μm were fabricated from poly(d,l-lactic acid-co-glycolic acid) (PLGA)-dioxane-water ternary systems via thermally induced phase separation (TIPS) without any surfactant or other additives. The effect on scaffold morphology of processing parameters including quenching temperature, polymer concentration, solvent composition and molecular weight, was investigated as a function of quenching time. The cloud-point temperature of the polymer solution was found to depend on polymer concentration, solvent composition, and polymer molecular weight. The water content in the solvent mixture had the greatest effect on the cloud-point temperature. The optimal quenching temperature for preparing macroporous inter-connected scaffolds from a 9 wt% PLGA solution (dioxane-water=87/13, by wt) was less than −7 °C. In low viscosity PLGA solutions, sedimentation of the polymer rich phase occurred due to the segregation of the separated phases under gravity. This led to the formation of scaffolds with irregular and closed pores.