Fabrication of bimodal porous PLGA scaffolds by supercritical CO2 foaming/particle leaching technique

Specific pore structure is a vital essential for scaffolds applied in tissue engineering. In this article, poly(lactide‐co‐glycolide) (PLGA) scaffolds with a bimodal pore structure including macropores and micropores to facilitate nutrient transfer and cell adhesion were fabricated by combining supercritical CO₂ (scCO₂) foaming with particle leaching technique. Three kinds of NaCl particles with different scales (i.e., 100–250, <75, <10 μm) were used as porogens, respectively. In particular, heterogeneous nucleation occurred to modify scCO₂ foaming/particle leaching process when NaCl submicron particles (<10 μm) were used as porogens. The observation of PLGA scaffolds gave a formation of micropores (pore size <10 μm) in the cellular walls of macropores (pore size around 100–300 μm) to present a bimodal pore structure. With different mass fractions of NaCl introduced, the porosity of PLGA scaffolds ranged from 68.4 ± 1.4 to 88.7 ± 0.4% for three NaCl porogens. The results of SEM, EDS, and in vitro cytotoxicity test of PLGA scaffolds showed that they had uniform structures and were compatible for cell proliferation with no toxicity. This novel scCO₂ foaming/particle leaching method was promising in tissue engineering due to its ability to fabricate scaffolds with precise pore structure and high porosity. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43644.     

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.     

Preparation and characterization of poly(vinyl chloride)‐graft‐acrylic acid membrane by electron beam

Poly(vinyl chloride) (PVC) was irradiated by electron beam in vacuum at 20 KGy to produce living free radicals, and then reacted with acrylic acid (AA) in solution to obtain the PVC‐g‐AA copolymers. The copolymers were characterized by Fourier transform infrared spectroscopy. Porous membranes were prepared from copolymers by the phase inversion technique. The morphology of PVC‐g‐AA membranes was studied by field emission scanning electron microscopy. The mean pore size and pore size distribution were determined by a mercury porosimeter. The mean pore size was 0.19 μm, and the bulk porosity was 56.02%. The apparent static water contact angle was 89.0°. The water drop penetration rate was 2.35 times to the original membrane. The maximum stress was 4.10 MPa. Filtration experiments were carried out to evaluate the fouling resistance of the PVC‐g‐AA membrane. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Plasma polymerization‐modified bacterial polyhydroxybutyrate nanofibrillar scaffolds

The design and the development of novel scaffold materials for tissue engineering have attracted much interest in recent years. Especially, the prepared nanofibrillar scaffold materials from biocompatible and biodegradable polymers by electrospinning are promising materials to be used in biomedical applications. In this study, we propose to produce low‐cost and cell‐friendly bacterial electrospun PHB polymeric scaffolds by using Alcaligenes eutrophus DSM 545 strain to PHB production. The produced PHB was characterized by Nuclear Magnetic Resonance (NMR) and Fourier Transform Infrared Spectroscopy (FTIR). Nanofibrous scaffolds were fabricated via electrospinning method that has a fiber diameter approximately 700–800 nm. To investigate cell attachment, cell growth, and antioxidant enzyme activity on positively and negatively charged PHB scaffold, PHB surface was modified by plasma polymerization technique using polyethylene glycol (PEG) and ethylenediamine (EDA). According to the results of superoxide dismutase (SOD) activity study, PEG‐modified nanofibrillar scaffolds indicated more cellular resistance against oxidative stress compared to the EDA modification. As can be seen in cell proliferation results, EDA modification enhanced the cell proliferation more than PEG modification, while PEG modification is better as compared with nonmodified scaffolds. In general, through plasma polymerization technique, surface modified nanofibrillar structures are effective substrates for cell attachment and outgrowth. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Specially elaborated thermally induced phase separation to fabricate poly(L‐lactic acid) scaffolds with ultra large pores and good interconnectivity

Poly(L ‐lactic acid) (PLLA) scaffolds with pore diameters from several micrometers to ～300 μm were fabricated by a specially elaborated thermally induced phase separation technique. Two different coarsening protocols, i.e., normal coarsening and multi‐step coarsening were compared in consideration of phase separation and domain growth. A normal coarsening route produced scaffolds with pore size from several micrometers to 150 μm depending on the coarsening time after phase separation, accompanying with the emergence of isolated pores at long time coarsening. Scaffolds with large pores with size up to ～300 μm were fabricated by the two‐step coarsening technique, e.g., the PLLA‐solvent (dioxane/water) system was coarsened at a temperature after phase separation for a period, followed by coarsening at a lower temperature for another period. In parallel with formation of the large pores, the interconnectivity between pores was also improved, which was evidenced by scanning electron microscopy, gelatin solution pervasion, and collagen entrapment. The present technique provides the ability to produce scaffolds with high purity, controllable microstructures, and ease of modification, and hence can be widely used in tissue engineering field. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 3336–3342, 2006     

Fabrication of a poly(ɛ‐caprolactone)/starch nanocomposite scaffold with a solvent‐casting/salt‐leaching technique for bone tissue engineering applications

A series of nanocomposite scaffolds of poly(?‐caprolactone) (PCL) and starch with a range of porosity from 50 to 90% were fabricated with a solvent‐casting/salt‐leaching technique, and their physical and mechanical properties were investigated. X‐ray diffraction patterns and Fourier transform infrared spectra confirmed the presence of the characteristic peaks of PCL in the fabricated scaffolds. Microstructure studies of the scaffolds revealed a uniform pore morphology and structure in all of the samples. The experimental measurements showed that the average contact angle of the PCL/starch composite was 88.05 ± 1.77°. All of the samples exhibited compressive stress/strain curves similar to those of polymeric foams. The samples with 50, 60, 70, and 80 wt % salt showed compressive‐load‐resisting capabilities in the range of human cancellous bone. With increasing porosity, a significant decrease in the mechanical properties of the scaffolds was observed. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43523.     

Effect of porosigen on the swelling behavior and drug release of porous N‐isopropylacrylamide/poly(ethylene glycol) monomethylether acrylate copolymeric hydrogels

A series of porous thermoreversible hydrogels were prepared from N‐isopropylacrylamide (90 mol %) and poly(ethylene glycol) methylether acrylate (10 mol %), which was derived from poly(ethylene glycol) monomethylether, N,N′‐methylenebisacrylamide, and porosigen, or poly (ethylene glycol) (PEG) with different molecular weights (MWs). The influence of pore volume in the gel on the physical properties, swelling kinetics, and solute permeation from these porous gels was investigated. The results show that the surface areas, pore volumes, and equilibrium swelling ratios for the porous gels increased with increasing MW of PEG, but the shear moduli and effective crosslinking densities decreased with increasing MW of PEG. The results from the dynamic swelling kinetics show that the transport mechanism was non‐Fickian. The diffusion coefficients of water penetrating into the gels increased with increasing pore volume of the gels. In addition, we also studied solute permeation through the porous gel controlled by temperature. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 5490–5499, 2006     

Thermosensitive poly(n‐isopropylacrylamide) hydrogels bonded on cellulose supports

A two‐step initiation and polymerization process was developed for the preparation of two series of hydrogel–cellulose composites with distinctively different morphologies and swelling behaviors. Hydroentangled cotton cellulose fibers were optimally initiated in 20 mM aqueous ammonium cerium(IV) nitrate for 15 min and then polymerized in aqueous solutions of N‐isopropylacrylamide (NIPAAm) monomer and N,N′‐methylene bisacrylamide (BisA) crosslinker. The extents of hydrogels on the cellulose solids could be controlled by variations in the concentrations of the monomer and crosslinker as well as the NIPAAm/BisA solution‐to‐solid ratios. The two series of hydrogel–cellulose composites formed were hydrogel‐covered/filled cellulose (I) and cellulose‐reinforced hydrogel (II) composites. Series I composites were synthesized with NIPAAm/BisA solutions below the liquid saturation level of the cellulose; this led to pore structures (size and porosity) that depended on both the extent and swelling of the grafted hydrogels. Series II composites were polymerized in the presence of excessive NIPAAm/BisA solutions to produce cellulose solids completely encapsulated in the hydrogels. All the cellulose‐supported hydrogels exhibited lower extents of phase transition over a wider temperature range (28–40°C) than the free poly(N‐isopropylacrylamide) hydrogels (32°C). These findings demonstrate that hydrogels can be used to control the pore structure of cellulose and can be supported with cellulose fibers. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 999–1006, 2003     

Morphology,wettability, and mechanical properties of polycaprolactone/hydroxyapatite composite scaffolds with interconnected pore structures fabricated by a mini‐deposition system

A new mini‐deposition system (MDS) was developed to fabricate scaffolds with interconnected pore structures and anatomical geometry for bone tissue engineering. Polycaprolactone/hydroxyapatite (PCL/HA) composites with varying hydroxyapatite (HA) content were adopted to manufacture scaffolds by using MDS with a porosity of 54.6%, a pore size of 716 μm in the x‐y plane, and 116 μm in the z direction. The water uptake ratio and compressive modulus of PCL/HA composite scaffold increase from 8 to 39% and from 26.5 to 49.8 MPa, respectively, as the HA content increases from 0 to 40%. PCL/HA composite scaffolds have better wettability and mechanical properties than pure PCL scaffold. A PCL/HA composite scaffold for mandible bone repair was successfully fabricated with both interconnected pore structures and anatomical shape to demonstrate the versatility of MDS. POLYM. ENG. SCI., 2012. © 2012 Society of Plastics Engineers     

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     

Physical and mechanical properties of the fully interconnected chitosan ice‐templated scaffolds

Porous chitosan scaffolds were prepared with a freeze‐casting technique with different concentrations, 1.5 and 3 wt %, and also different cooling rates, 1 and 4°C/min. The pore morphology, porosity, pore size, mechanical properties, and water absorption characteristics of the scaffolds were studied. Scanning electron microscopy images showed that the freeze‐cast scaffolds were fully interconnected because of the existence of pores on the chitosan walls in addition to many unidirectionally elongated pores. Increases in the chitosan concentration and freezing rate led to elevations in the thickness of the chitosan walls and reductions in the pores size, respectively. These two results led to the enhancement of the compressive strength from 34 to 110 kPa for the scaffolds that had 96–98% porosity. Also, augmentation of the chitosan concentration and decreases in the freezing rate led to the reduction of the number of pores on the chitosan walls. Furthermore, the volume of water absorption increased with a reduction in the chitosan concentration and cooling rate from 690 to 1020%. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41476.     

Preparation and characterization of starch‐based composite films reinforced by corn and wheat hulls

Biodegradable films, with starch as a matrix, were developed and reinforced with wheat and corn hulls. The effect of the particle size of the filler on the microstructure and mechanical and barrier properties of starch‐based films was investigated. We observed that the addition of hulls enhanced the modulus, tensile strength, and impact strength of the starch matrix at the expense of its elongation. The water‐vapor transmission rate results show that corn starch was more efficient in reducing the water‐vapor permeability than wheat hulls. Scanning electron microscopy observations indicated that the compatibility of both fillers with the matrix was quite good; this was expected because all of the components used in this study were hydrophilic and exhibited polar behavior. Optical microscopy and X‐ray diffraction observations indicated that the processing conditions did not affect the crystalline and geometric structures of the hulls. Because all of the components used in this study were from food resources, the films could also be used for edible packaging. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45159.     

Ultraporous poly(lactic acid) scaffolds with improved mechanical performance using high‐pressure molding and salt leaching

A novel processing technique, i.e. high‐pressure compression molding/salt leaching, was developed to fabricate ultraporous poly(lactic acid) (PLA) scaffolds. The optimized composition was studied in relation to the porosity, pore morphology, thermal property, and mechanical performance of the PLA scaffolds. At a porogen (CaCO₃) content of 90 wt %, the scaffolds have an interconnected open pore structure and a porosity above 80%. It was truly interesting that the structural stability of high‐pressure molded scaffolds was remarkably improved based on the fact that its glass transition temperature (83.5°C) increased about 20°C, as compared to that of the conventional compression‐molded PLA (60°C), which is not far from physiological temperature (～37°C) at the risk of structural relaxation or physical aging. More importantly, the mechanical performance of PLA scaffolds was drastically enhanced under optimized processing conditions. At pressure and temperature of 1000 MPa and 190°C, the porous PLA scaffolds attained a storage modulus of 283.7 MPa, comparable to the high‐end value of trabecular bone (250 MPa) ever reported. In addition, our prepared PLA scaffolds showed excellent cellular compatibility and biocompatibility in vitro tests, further suggesting that the high‐pressure molded PLA scaffolds have high potential for bone tissue engineering applications. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 3509–3520, 2013     

Characterization of 3D elastic porous polydimethylsiloxane (PDMS) cell scaffolds fabricated by VARTM and particle leaching

In this study, elastic porous polydimethylsiloxane (PDMS) cell scaffolds were fabricated by vacuum‐assisted resin transfer moulding (VARTM) and particle leaching technologies. To control the porous morphology and porosity, different processing parameters, such as compression load, compression time, and NaCl particle size for preparing NaCl preform, were studied. The porous structures of PDMS cell scaffolds were characterized by scanning electron microscopy (SEM). The properties of PDMS cell scaffolds, including porosity, water absorption, interconnectivity, compression modulus, and compression strength were also investigated. The results showed that after the porogen–NaCl particles had been leached, the remaining pores had the sizes of 150–300, 300–450, and 450–600 μm, which matched the sizes of the NaCl particles. The interconnectivity of PDMS cell scaffolds increases with an increase in the size of NaCl particles. It was also found that the smaller the size of the NaCl particles, the higher the porosity and water absorption of PDMS cell scaffolds. The content of residual NaCl in PDMS/NaCl scaffolds reduces under ultrasonic treatment. In addition, PDMS scaffolds with a pore size of 300–450 μm have better mechanical properties compared to those with pore sizes of 150–300 and 450–600 μm. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42909.     

Application of low loading of collagen in electrospun poly[(l‐lactide)‐co‐(ε‐caprolactone)] nanofibrous scaffolds to promote cellular biocompatibility

Electrospinning of various polymers has been used to produce nanofibrous scaffolds that mimic the extracellular matrix and support cell attachment for the potential repair and engineering of nerve tissue. In the study reported here, an electrospun copolymer of l ‐lactide and ε‐caprolactone (67:33 mol%) resulted in a nanofibrous scaffold with average fibre diameter and pore size of 476 ± 88 and 253 ± 17 nm, respectively. Blending with low loadings of collagen (<2.5% w/w) significantly reduced the average diameter and pore size. The uniformity of fibre diameter distributions was supported with increasing collagen loadings. The nanofibrous scaffolds significantly promoted the attachment and proliferation of olfactory ensheathing cells compared to cells exhibiting asynchronous growth. Furthermore, analysis of cell health through mitochondrial activity, membrane leakage, cell cycle progression and apoptotic indices showed that the nanofibrous membranes promoted cell vigour, reducing necrosis. The study suggests that the use of more cost‐effective, low loadings of collagen supports morphological changes in electrospun poly[(l ‐lactide)‐co‐(ε‐caprolactone)] nanofibrous scaffolds, which also support attachment and proliferation of olfactory ensheathing cells while promoting cell health. The results here support further investigation of the electrospinning of these polymer blends as conduits for nerve repair. © 2013 Society of Chemical Industry     

A new method of preparing superabsorbent PVF porous foam through the simultaneous acidification of water glass solution–aspect of environmental protection

To reduce the wastewater pollution problem, silica particles that have resulted from simultaneous sulfuric acidification of water glass solution serve as the pore‐forming agent for preparing superabsorbent PVF/SiO₂ foam in this study. This is a departure from the traditional porous PVF/starch foam's manufacture method. The pore structure of PVF/SiO₂ foam is very different from that of PVF/starch foam. The effect of the concentration of these pore‐forming agents on the pore structure, mechanical modulus, and water adsorption capacity of PVF/starch and PVF/SiO₂ foams are investigated in this study. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39894.     

Fabrication of bioceramic scaffolds with pre-designed internal architecture by gel casting and indirect stereolithography techniques

A new technique of combining the gel casting and indirect rapid prototyping methods was utilized to fabricate macroporous β-tricalcium phosphate (β-TCP) scaffolds, which provided an excellent control over the internal architecture of scaffolds and enhanced their mechanical properties. A stereolithography apparatus was used to produce resin molds for ceramic gel casting. These molds were filled with a water based thermosetting ceramic slurry which solidifies inside the mold. After burning the resin mold and sintering, the β-TCP scaffolds with designed pore architecture were obtained. The pore morphology, size, and distribution of the resulting scaffolds were characterized using a scanning electron microscope. X-ray diffraction was used to determine the crystal structure and chemical composition of scaffolds. The mechanical measurements showed that the average compressive strength was 16.1 ± 0.8 MPa.     

Optimal design on the mechanical and thermal properties of porous alumina ceramics based on fractal dimension analysis

In order to investigate the relationship between pore structure and thermal conductivity as well as mechanical strength, porous alumina ceramics (PAC) with various pore structures were fabricated, using starch as the pore‐forming agent. Fractal theory was employed to characterize the pore size distribution more accurately than ever used parameters. The results show that the increase in starch content in PAC leads to an enhanced porosity, a higher mean pore size, and reduced fracture dimension, thermal conductivity and strength. The fractal analysis indicated that the fractal dimension decreases gradually and reaches its minimum value with increasing the starch content up to 25 wt%, but the further incorporation results in an opposite trend. It is suggested from micro‐pore fractographic analysis that the optimization of both thermal insulation performance and mechanical strength are positively correlated with the increase in the mean pore size and proportion of 2‐14 μm pores but negatively corrected with the porosity. These results provide a new perspective and a deeper understanding for fabrication of PAC with both excellent thermal insulation and mechanical performance.     

The Effect of Pore Size Distribution and l-Lysine Modified Apatite Whiskers (HAP) on Osteoblasts Response in PLLA/HAP Foam Scaffolds Obtained in the Thermally Induced Phase Separation Process

In this research, we prepared foam scaffolds based on poly(l-lactide) (PLLA) and apatite whiskers (HAP) using thermally induced phase separation technique supported by the salt leaching process (TIPS-SL). Using sodium chloride having a size of (a) 150–315 μm, (b) 315–400 μm, and (c) 500–600 μm, three types of foams with different pore sizes have been obtained. Internal structure of the obtained materials has been investigated using SEM as well as μCT. The materials have been studied by means of porosity, density, and compression tests. As the most promising, the composite prepared with salt size of 500–600 μm was prepared also with the l-lysine modified apatite. The osteoblast hFOB 1.19 cell response for the scaffolds was also investigated by means of cell viability, proliferation, adhesion/penetration, and biomineralization. Direct contact cytotoxicity assay showed the cytocompatibility of the scaffolds. All types of foam scaffolds containing HAP whiskers, regardless the pore size or l-lysine modification induced significant stimulatory effect on the cal-cium deposits formation in osteoblasts. The PLLA/HAP scaffolds modified with l-lysine stimulated hFOB 1.19 osteoblasts proliferation. Compared to the scaffolds with smaller pores (150–315 µm and 315–400 µm), the PLLA/HAP foams with large pores (500–600 µm) promoted more effective ad-hesion of osteoblasts to the surface of the biomaterial.     

Morphological study on the reactivity of styrene‐divinylbenzene copolymers in a chloromethylation reaction

Styrene‐divinylbenzene (S‐DVB) copolymers with different kinds of porous structures were synthesized by aqueous suspension polymerization using n‐heptane as the pore forming agent. The amount of this solvent (monomer dilution degree) and the DVB content in the organic phase were varied. The combination of three different dilution degree values and three DVB contents yielded three series of copolymers with a variety of porous structures. The three series were composed by copolymers with pore diameters (D) in the following ranges: D < 500 Å, 500 < D < 1000 Å, and D > 1000 Å, respectively. The effect of synthesis conditions on the pore size distribution and on the copolymer matrix rigidity was evaluated. These copolymers were submitted to a chloromethylation reaction with a paraformaldehyde/gaseous HCl mixture in the presence of zinc chloride as a Lewis acid catalyst and 1,2‐dichloroethane as solvent. The effect of the copolymer porosity on the chloromethylation reaction extension was evaluated. It was possible to observe that a gel copolymer with a high swelling capacity in the reaction medium achieved the same chloromethylation yield observed for a high porous copolymer. This result thus indicates that, in the case of the chloromethylation reaction studied here, the high swelling capacity of the gel copolymer can counterbalance its limited surface area, turning this type of polymer structure as reactive as a macroporous one. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010