Solvent‐Free Generation of Foamed Microcapillary Films with a Dual Network of Interconnected Pores and Internal Channels

A dual‐pore network is favored in applications such as tissue engineering scaffolds. In this paper, foamed microcapillary films (FMCFs) are prepared based on a poly(lactic acid)/poly(butylene succinate) blend using melt extrusion and batch foaming with supercritical carbon dioxide. Such films are characterized by multiple hollow microcapillaries (diameter of 100–360 µm) connected with cells (size of 3–194 µm, open‐cell content of over 80%) within the scaffold. By plugging the ends of the MCF before foaming, the formation of a solid skin layer is successfully avoided. Furthermore, the diameter of the microcapillaries of an FMCF can be adjusted using the designed foaming strategy. The effects of the foaming condition on the FMCF foaming behavior are also investigated. When other conditions are fixed, the foaming behavior changes dramatically when the foaming temperature changes within the range of 120–123 °C.     

Fabrication and characterization of honeycomb β-tricalcium phosphate scaffolds through an extrusion technique

In this study, for the first time honeycomb β-tricalcium phosphate (β-TCP) scaffolds were fabricated through an extrusion technique. The physicochemical properties and cell behaviors of the honeycomb β-TCP scaffolds were investigated. The results showed that scaffolds were characterized by ordered channel-like macropores and unidirectional interconnection. The pore structure and mechanical strength could be tailored by changing the parameters of extrusion molds. The pore size of scaffolds was in the range of 400–800 µm approximately, while their compressive strength parallel to the pore direction and porosity ranged from 14 to 20 MPa and 60–70%, respectively. The in vitro cell behavior demonstrated that cells could well attach on the surfaces and grow into the inner channel-like pores of thescaffolds; the scaffolds with higher porosity showed better cell proliferation but poorer cell differentiation. The honeycomb scaffolds fabricated by extrusion technique are potential candidate for bone tissue engineering.     

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.     

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     

Polymeric scaffolds based on blends of poly-l-lactic acid (PLLA) with poly-d-l-lactic acid (PLA) prepared via thermally induced phase separation (TIPS): demixing conditions and morphology

Porous scaffolds based on blends of high crystalline Poly-l-lactic acid (PLLA) with low crystalline poly-d-l-lactic acid (PLA) were prepared via Thermally Induced Phase Separation (TIPS), with the aim of exploring the possibility to control the degradation behaviour of the PLA-based scaffold, simultaneously preserving the morphological characteristics required for tissue engineering applications. Porous foams with different PLLA/PLA weight ratios (from 95/5 to 60/40) were produced and characterised in terms of pore size, porosity, and thermal properties. The scaffolds present an open porosity, with average pore sizes ranging from 30 to 70 μm. Results showed that, when dealing with a PLLA/PLA blend, some relevant processing conditions of the preparation process (above all demixing temperature and total polymer concentration) must be carefully tuned, in order to attain suitable structures in term of pore size and porosity. In particular, with increasing amounts of PLA in a PLLA/PLA blend, the demixing temperature must be decreased and the overall polymer concentration decreased. Moreover, a preliminary investigation regarding the in vitro biodegradation rate of the blends was attempted, based on the determination of the crystallinity through wide angle X-ray diffractometry.     

Tailoring the pore structure of PCL scaffolds for tissue engineering prepared via gas foaming of multi-phase blends

The aim of this study was the design of poly(ε-caprolactone) (PCL) scaffolds characterized by well controlled pore structures obtained by gas foaming of multi-phase blends of PCL and thermoplastic gelatin (TG). Co-continuous blends made of PCL and TG were prepared by melt mixing and, subsequently gas foamed in an autoclave to induce the formation of the porous network. A mixture of N₂ and CO₂ was used as blowing agent and the foaming process performed at temperature higher than PCL melting, in the range 70–110 °C. The foams were finally soaked in water at 37 °C to selectively extract the TG and achieve the final pore structure. The results of this study demonstrated that the proposed approach allowed to tailor the micro-structural properties of PCL scaffolds for tissue engineering.     

Investigation of PLA-based scaffolds fabricated via SVM rapid prototyping

Poly-lactic acid (PLA) is a biodegradable polymer that has been well accepted as a tissue engineering scaffold material. Recently, PLA has been applied in selective vacuum manufacturing (SVM), a new RP technique being developed, for fabricating scaffold. For this RP technique to be accepted for this purpose, its fabricated scaffolds must be tested for their properties. This paper presents an investigation of the properties of scaffolds fabricated from SVM technique. The results illustrated that the fabricated PLA scaffolds had porous structure. The porosity was about 71.65% with pore size ranged from 20 to 90???m. The compressive modulus of elasticity was 2.07?±?0.25?MPa, lying within the lower range of mechanical properties reported for soft tissue application. An indirect cytotoxicity test showed the cell viability of 75.92% which means that the specimens posed no threat to the cells and could be used as scaffolds for mammalian tissue culture.     

Novel fabrication of hierarchically porous hydroxyapatite scaffolds with refined porosity and suitable strength

Based on extrusion deposition and foaming technique, a novel method for biological hydroxyapatite (HA) scaffolds was introduced in this paper. The scaffolds were primarily characterised by interconnected and hierarchically porous structures with high porosity, adjustable distribution of pore sizes, as well as considerable mechanical strength. In order to confirm that fine control of bulk porosity and mechanical strength was possible and feasible, further analysis of obtained scaffolds was carried out by field emission scanning electron microscope (FESEM), compressive test and calculation of volumetric shrinkage; in particular, the additional porosity resulting from the introduction of pore former was evaluated. The results indicated that this method can have a great potential to construct HA scaffolds of suitable quality for spongy bone in bone tissue engineering.     

Blending and foaming thermoplastic starch with poly (lactic acid) by CO2-aided hot melt extrusion

Biomaterials are materials that can be biodegradable or obtained from renewable resources. Among them, poly (lactic acid) (PLA) and thermoplastic starch (TPS) represent an interesting alternative to replace petro-sourced thermoplastics. In this study, blends made by TPS addition to PLA were subjected to a foaming process using supercritical CO₂-aided extrusion. Extruder die temperature and CO₂ content were the most prominent parameters explaining the structure of the foams obtained. Both parameters were intimately linked since the CO₂ flow depends on the melt temperature, the lower the temperature, the higher the CO₂ solubility. Therefore, the die temperature was chosen to pilot the process. Whatever the experimental conditions, a 50/50 (in wt%) blend was poorly foamed due to the strong incompatibility between both biopolymers. However, the blend made of 80 wt% PLA and 20 wt% TPS gave evenly foamed samples. In terms of expansion and type of porosity this blend behaved like pure PLA with high porosity, up to 96%, and the presence of a threshold die temperature separating a close cell porosity at lowest temperatures and an open cell structure above the threshold. This temperature threshold was however significantly lower to that obtained with pure PLA.     

微孔发泡制备聚乳酸开孔材料

微孔发泡技术避免使用有机溶剂和高温过程,在生物组织工程支架材料的制备方面具有广阔的应用前景.研究采用DOE(试验设计)方法研究发泡温度、饱和压力及发泡时间等工艺参数对开孔度及表观密度的影响程度,根据DOE试验结果确定试验空间内的最佳工艺务件,并对聚乳酸材料的开孔机理进行探讨.     

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     

聚乳酸扩链改性及其挤出发泡的研究

采用扩链剂对聚乳酸（PLA）进行扩链改性,研究了扩链剂对PLA流变性能的影响。采用3种不同类型的化学发泡剂：发泡剂A（发泡母粒）、发泡剂B\[自制复合发泡剂：偶氮二甲酰胺（AC发泡剂）/碳酸氢钠(NaHCO3)\]、发泡剂C(自制改性AC发泡剂),利用单螺杆挤出机对PLA进行挤出发泡。采用扫描电子显微镜观察分析了发泡材料的断面泡孔结构。结果表明,加入扩链剂可有效提高PLA的熔体强度和黏度及降低其熔体流动速率,改善PLA的发泡效果,扩链剂含量为0.8份（质量分数,下同）时,发泡材料的发泡效果最好;实验所用的3种发泡剂中,发泡剂C的发泡效果最好,发泡剂含量为1.5份时,发泡样品的表观密度较小（0.6 g/cm3）,泡孔直径最小(约为57 μm),泡孔密度最大（约为7.69×10^6个/cm3）,泡孔分布均匀,无明显泡孔破裂和连通现象。     

A novel method for the determination of cell infiltration into nanofiber scaffolds using image analysis for tissue engineering applications

One of the major themes in tissue engineering is scaffold fabrication. The porosity and pore size of scaffolds play a critical role in tissue engineering. Different methods are used to measure the porosity and pore size of scaffolds, although none can predict the cell infiltration for various cell sizes, shapes, and configurations. The aim of this study was to predict the cell infiltration of various cells with different sizes, shapes, and configurations through the use of image analysis. In this study, cell models were used to predict cell infiltration into nanofiber scaffolds. The results of this study showed that with increases in the cell size and the number of layers of nanofibers, the number of cells that could infiltrate the scaffolds decreased. In addition, the cell configuration had some effect on cell infiltration into the nanofiber scaffolds. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Solid-state supercritical CO2 foaming of PCL and PCL-HA nano-composite: Effect of composition, thermal history and foaming process on foam pore structure

In this work we investigated the solid-state supercritical CO₂ (scCO₂) foaming of poly(?-caprolactone) (PCL), a semi-crystalline, biodegradable polyester, and PCL loaded with 5 wt% of hydroxyapatite (HA) nano-particles.In order to investigate the effect of the thermal history and eventual residue of the crystalline phase on the pore structure of the foams, samples were subjected to three different cooling protocols from the melt, and subsequently foamed by using scCO₂ as blowing agent. The foaming process was performed in the 37-40 °C temperature range, melting point of PCL being 60 °C. The saturation pressure, in the range from 10 to 20 MPa, and the foaming time, from 2 to 900 s, were modulated in order to control the final morphology, porosity and pore structure of the foams and, possibly, to amplify the original differences among the different samples.The results of this study demonstrated that by the scCO₂ foaming it was possible to produce PCL and PCL-HA foams with homogeneous morphologies at relatively low temperatures. Furthermore, by the appropriate combination of materials properties and foaming parameters, we prepared foams with porosities in the 55-85% range, mean pore size from 40 to 250 μm and pore density from 10⁵ to 10⁸ pore/cm³. Finally, we also proposed a two-step depressurization foaming process for the design of bi-modal and highly interconnected foams suitable as scaffolds for tissue engineering.     

Preparation and properties of foamed cellulose acetate/polylactic acid blends

In order to improve the foaming performance of pure cellulose acetate (CA), blends were prepared by mixing polylactic acid (PLA) in CA and foamed by supercritical CO₂ (ScCO₂) in this study. The effect of PLA content (percentage by mass of blend) on structure, thermal properties, rheological properties, foaming properties and mechanical properties of the blends was investigated. The results showed that the addition of PLA destroyed the original hydrogen bonds of CA, while the blends had good crystallization properties. At the same time, compared with pure CA, the glass transition temperature (T_g) of the blends decreased, and the initial decomposition temperature (T₀) was reduced from 349.41°C (pure CA) to 334.68°C (CA/20%PLA). In addition, the rheological properties of the blends were improved, and the viscosity was reduced, which was obviously beneficial to foaming process. The pore size and density of the foamed blends both reached the maximum value at 20%PLA. The presence of PLA could degrade the mechanical properties of the blends. However, the overall drop (1.01 KJ/m²) of impact strength of the blends after foaming is much smaller than that before foaming (12.11 KJ/m²), indicating that the improvement of foaming performance was beneficial to improve its impact strength.     

Control of the structure and mechanical property of porous WS<Subscript>2</Subscript> scaffold during freeze casting

Porous WS₂ scaffolds with aligned lamellar pore were fabricated by freeze casting, and the pore morphology and size can be well controlled by adjusting the processing parameters during freeze casting process. The results indicated that the porosity and the compressive strength of porous WS₂ were greatly affected by the concentration of gelatin. As the gelatin addition increased from 1 to 5 wt%, the porosity of porous WS₂ scaffolds with initial solid content of 3 vol% decreased from 95.12 to 90.23%, and their compressive strength increased from 0.22 to 1.16 MPa. Moreover, the lamellar spacing and wall thickness could be tailored from 90 to 320 and 5 to 30 μm respectively by changing the cooling temperature. And the compressive strength of scaffolds has a slight increase with the decreases of cooling temperature. The porous WS₂ scaffold with fine aligned lamellar structure and proper compressive strength are expected to be used for scaffold materials.     

Synthesis and characterisation of β-TCP/bioglass/zirconia scaffolds

Tricalcium phosphate scaffolds reinforced with bioglass were characterised morphologically, physically, and mechanically. The scaffolds were fabricated through powder technology and the polymer foaming technique using 80?wt-% of β-TCP and 20?wt-% of phosphate-based bioglass doped with zirconia in various amounts (0, 0.25, 0.5, 0.75, and 1.0?wt-%). The foaming agent was varied (1, 1.5, 2, 2.5, and 3?wt-%) to determine the optimal amount that ensured an interconnected porosity and pore size suitable for increasing osteoconduction and cell attachment. Promising samples for tissue engineering applications showed a pore size ranging from 1.41 to 303?μm, total porosity of 50–53%, compressive strength values between 0.6 and 1?MPa, Young’s modulus from 357 to 574?MPa, and excellent interconnectivity.     

Cellular mullite materials processed by direct foaming and protein casting

In this paper, cellular mullite bodies were developed by thermal direct-consolidation of foamed aqueous mullite-bovine serum albumin (BSA) and mullite-BSA-methylcellulose suspensions, burning out (650 °C, 2 h) and sintering (1600 °C, 2 h). Some modifications to the shaping route conventionally used in protein casting were incorporated in the proposed processing to obtain bodies with controlled and homogeneous microstructures. The materials were characterized by porosity measurements, analysis of phases by XRD, and microstructural analysis by SEM and Hg-porosimetry. Characteristic parameters of cell size distributions, percentage of open and closed cells, window size and interstitial pore size distributions, and microstructural features of the mullite matrix were determined. Moreover, basic 2D cell size parameters and global 3D stereological parameters were analysed. The obtained results showed that mullite bodies with hierarchical porosity and different microstructural features were developed from the design and control of processing routes, which use BSA as a foaming and binder/consolidator agent.     

Design and preparation of μ‐bimodal porous scaffold for tissue engineering

The aim of this study was to prepare poly‐?‐caprolactone (PCL) foams, with a well‐defined micrometric and bimodal open‐pore dimension distribution, suitable as scaffolds for tissue engineering. The porous network pathway was designed without using toxic agents by combining gas foaming (GF) and selective polymer extraction techniques. PCL was melt‐mixed with thermoplastic gelatin (TG) in concentrations ranging from 40 to 60 wt %, to achieve a cocontinuous blend morphology. The blends were subsequently gas foamed by using N₂‐CO₂ mixtures, with N₂ amount ranging from 0 to 80 vol %. Foaming temperature was changed from 38 to 110°C and different pressure drop rates were used. After foaming, TG was removed by soaking in H₂O. The effect of blend compositions and GF process parameters on foam morphologies was investigated. Results showed that different combinations of TG weight ratios and GF parameters allowed the modulation of macroporosity fraction, microporosity dimension, and degree of interconnection. By optimizing the process parameters it was possible to tailor the morphologies of highly interconnected PCL scaffolds for tissue engineering. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Foamability and viscosity behavior of extrusion foamed PLA–pulp fiber biocomposites

This study addresses the effect of fiber reinforcement, chain extension, and physical foaming agent type on foam morphology and viscosity behavior of pulp fiber reinforced poly(lactic acid) (PLA) biocomposites. PLA reinforced with 0, 10, and 20 wt % of bleached kraft pulp fibers with and without chain extender were foamed using two different physical foaming agents (carbon dioxide and isobutane) by extrusion foaming. Densities, foam morphologies, and viscosities were systematically analyzed and compared from the produced foams. As a conclusion, low-density foams are produced with both foaming agents and fiber levels, fiber addition limiting cell growth. Isobutane provides better dimensional stability with narrower cell size distribution, whereas carbon dioxide enables lower foaming temperature. Chain extension is essential to achieve foam with low density and good cell structure. Contrary to nonchain extended PLA, addition of fibers reduced the viscosity of chain extended PLA. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 48202.