Fabrication of Biodegradable Polyurethane Foam Scaffolds with Customized Shapes and Controlled Mechanical Properties by Gas Foaming Technique

Poly(ε-caprolactone) (PCL)-based polyurethane (PU) foam scaffolds with different mechanical properties are fabricated using a gas foaming technique to use as porous substitutes for ear or bone with cartilage. PCL diol or triol is used as a polyol in PU foam for biocompatibility and biodegradation, with an aqueous gelatin solution as a blowing agent. The highly porous inner and outer structures of the scaffolds are developed by employing a silicone surfactant and sulfuric acid, respectively. The PU scaffolds prepared by PCL diol show ductile and flexible properties, whereas the PU scaffolds prepared by PCL triol exhibit high compression strength. In vitro test reveals the low toxicity of the PU scaffolds and the high ALP activity of MC3T3-E1 cells in the PU scaffold prepared by PCL triol. By taking advantage of the difference in mechanical properties, customized PU scaffolds with ear or bone shapes are fabricated using a silicone mold. The PU scaffolds with two compartments of PCL diol and triol (corresponding to cartilage and bone, respectively) are fabricated as a substitute for bone with cartilage. It is believed that the PU scaffolds with highly porous structure and controlled mechanical properties have wide potential application for tissue engineering.     

Determination of cytocompatibility and osteogenesis properties of in situ forming collagen-based scaffolds loaded with bone synthesizing drug for bone tissue engineering

Bone tissue engineering using in situ forming 3D scaffolds can be an alternative to surgically treated scaffolds. This work aimed to develop in situ forming scaffolds using poly (lactic-co-glycolic acid) and a bone synthesizing drug (risedronate) with or without the porogenic agent (collagen). Hybrid scaffolds were formed through solvent-induced phase inversion technique and were morphologically evaluated using scanning electron microscopy (SEM). The effect of scaffolds on Saos-2 cell line viability using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide test besides their effect on cell growth using fluorescence microscope was assessed. Furthermore, alkaline phosphatase (ALP) activity as well as Ca²⁺ deposition on the scaffolds was evaluated. SEM images revealed the porous structure for collagen-based scaffolds. Saos-2 cell proliferation was significantly enhanced with risedronate-loaded scaffolds compared to those lacking the drug. Porous collagen-based scaffolds were more favorable for both the cell growth and the promotion of ALP activity. Furthermore, collagen-based scaffolds promoted the Ca²⁺ deposition compared to their counterparts without collagen. Such results suggest that collagen-based scaffolds offer excellent biocompatibility for bone regeneration, where this biocompatible nature of scaffold leads to the proliferation of cells that lead to the deposition of mineral on the scaffold. Such in situ forming 3D scaffolds provide a promising noninvasive approach for bone tissue engineering.     

Sustained release of dexamethasone from drug‐loading PLGA scaffolds with specific pore structure fabricated by supercritical CO2 foaming

Inducing differentiation of bone marrow stem cells to generate new bone tissue is highly desirable by controlling the release of some osteoinductive or osteoconductive factors from porous scaffolds. In this study, dexamethasone was selected as a representative of small molecule drugs and dexamethasone‐loading porous poly(lactide‐co‐glycolide) (PLGA) scaffolds were successfully fabricated by supercritical CO₂ foaming. Scanning electron microscopy images showed that scaffolds had rough and relatively interconnected pores facilitating cells adhesion and growth. Specially, dexamethasone which was incorporated into PLGA matrix in a molecularly dispersed state could serve as a nucleation agent to be helpful for the formation of interconnected pores. Dexamethasone‐loading porous PLGA scaffolds exhibited sustained release profile, and the delivery of dexamethasone from porous scaffolds could last for up to 2 months. The cumulative released amount of dexamethasone was relevant with drug loading capacity (1.66%–2.95%) and pore structure of scaffolds; while the release behavior was anomalous (non‐Fickian) transport by fitting with the simple exponential equation, which had a diffusional exponent n higher than 0.5. It is feasible to fabricate drug‐loading porous scaffolds by supercritical CO₂ foaming with specific pore structure and sustained release profile, which can be well applied in bone tissue engineering. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46207.     

In vitro hydrolysis and magnesium release of poly(d,l‐lactide‐co‐glycolide)‐based composites containing bioresorbable glasses and magnesium hydroxide

Magnesium is important for both bone growth and cartilage formation. However, the postoperative intake of antibiotics such as quinolones may cause a reduction in magnesium levels in tissue. The addition of magnesium to scaffolds may therefore be beneficial for the regeneration of osteochondral defects. In this study, porous composite scaffolds were produced by gas foaming of poly(d ,l ‐lactide‐co‐glycolide) (PLGA) rods with magnesium‐containing bioresorbable glasses and magnesium hydroxide as fillers. The in vitro hydrolytical degradation of the composite scaffolds in Tris buffer was followed over a 10‐week period. Mg²⁺ was released in a controlled manner from the scaffolds with varying release profiles between the different materials. Higher glass content resulted in a reduced mass loss compared to scaffolds with lower glass content. As a result of the foaming method, the scaffolds shrank initially, without evidence that the addition of hydrophilic fillers would decrease the initial shrinkage. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42646.     

A novel thermoplastic polyurethane scaffold fabrication method based on injection foaming with water and supercritical carbon dioxide as coblowing agents

Injection foaming is an method for mass producing lightweight, foamed plastic components with excellent dimensional stability while using less material and energy. In this study, a novel injection foaming method employing supercritical CO₂ (scCO₂) and water as coblowing agents was developed to produce thermoplastic polyurethane (TPU) components with a uniform porous structure and no solid skin. Various characterization techniques were employed to investigate the cell morphology, crystallization behavior, and static and dynamic mechanical properties of solid injection molded samples, foamed samples using CO₂ or water as a single blowing agent, and foamed samples using both CO₂ and water as coblowing agents. When compared with CO₂ foamed samples, samples produced by the coblowing method exhibited much more uniform cell morphologies without a noticeable reduction in mechanical properties. Moreover, these TPU samples had almost no skin layer, which permitted the free transport of nutrients and waste throughout the samples. Such a mass‐produced, skin‐free structure is desirable in tissue engineering. In this study, the biocompatibility of the scaffolds was confirmed and the effect of these blowing agents on the TPU foaming behavior was studied. POLYM. ENG. SCI., 54:2947–2957, 2014. © 2014 Society of Plastics Engineers     

Supercritical CO2 deposition and foaming process for fabrication of biopolyester–ZnO bone scaffolds

Subsequent supercritical CO₂‐assisted deposition and foaming process followed by in situ synthesis was used to fabricate functional polylactide (PLA) and polylactide–poly(?‐caprolactone) (PLA–PCL) bone scaffolds. Deposition of zinc bis(2‐thenoyltrifluoroacetonate) as a ZnO precursor onto biopolyester substrates (30 MPa; 110 °C) was followed by fast depressurization to create cellular structure. Contact time was optimized regarding the deposition yield (2 h), while PCL content in PLA was varied (1–10 wt %). Scaffolds impregnated with the precursor were treated with hydrazine alcoholic solution to obtain biopolyester–ZnO composites. Precursor synthesis and deposition onto the scaffolds was confirmed by Fourier‐transform infrared. Processed scaffolds had micron‐sized pores (d₅₀ ～ 20 μm). High open porosity (69–77%) and compressive strength values (2.8–8.3 MPa) corresponded to those reported for trabecular bone. PLA blending with PCL positively affected precursor deposition, crystallization rate, and compressive strength of the scaffolds. It also improved PLA surface roughness and wettability which are relevant for cell adhesion. ZnO improved compressive strength of the PLA scaffolds without significant effect on thermal stability. Analysis of structural, thermal, and mechanical properties of biopolyester–ZnO scaffolds testified a great potential of the obtained platforms as bone scaffolds. Proposed processing route is straightforward and ecofriendly, fast, easy to control, and suitable for processing of thermosensitive polymers. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45824.     

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.     

Mechanical modeling of silk fibroin/TiO2 and silk fibroin/fluoridated TiO2 nanocomposite scaffolds for bone tissue engineering

Biocompatible and biodegradable three-dimensional scaffolds are commonly porous which serve to provide suitable microenvironments for mechanical supporting and optimal cell growth. Silk fibroin (SF) is a natural and biomedical polymer with appropriate and improvable mechanical properties. Making a composite with a bioceramicas reinforcement is a general strategy to prepare a scaffold for hard tissue engineering applications. In the present study, SF was separately combined with titanium dioxide (TiO₂) and fluoridated titanium dioxide nanoparticles (TiO₂-F) as bioceramic reinforcements for bone tissue engineering purposes. At the first step, SF was extracted from Bombyx mori cocoons. Then, TiO₂ nanoparticles were fluoridated by hydrofluoric acid. Afterward, SF/TiO₂ and SF/TiO₂-F nanocomposite scaffolds were prepared by freeze-drying method to obtain a porous microstructure. Both SF/TiO₂ and SF/TiO₂-F scaffolds contained 0, 5, 10, 15 and 20 wt% nanoparticles. To evaluate the efficacy of nanoparticles addition on the mechanical properties of the prepared scaffolds, their compressive properties were assayed. Likewise, the pores morphology and microstructure of the scaffolds were investigated using scanning electron microscopy. In addition, the porosity and density of the scaffolds were measured according to the Archimedes’ principle. Afterward, compressive modulus and microstructure of the prepared scaffolds were evaluated and modeled by Gibson–Ashby’s mechanical models. The results revealed that the compressive modulus predicted by the mechanical model exactly corresponds to the experimental one. The modeling approved the honeycomb structure of the prepared scaffolds which possess interconnected pores.

     

Bioactive Ceramic/Polyamide 6 Scaffold for Bone Regeneration: In vitro and in vivo Evaluation

A porous scaffold of bio-ceramic/polyamide 6 (PA 6) has been fabricated through a thermally induced phase separation technique. The scaffold was characterized by XPS, SEM and mechanical test. The results revealed that bio-ceramic/PA 6 scaffold had an interconnected porous structure with a porosity of about 78%. Moreover, bio-ceramic/PA 6 scaffolds were cultured with BMSCs to investigate their in vitro cytocompatibility, and they were implanted in subcutaneous sites of mice for 4 and 8 weeks to evaluate their in vivo histocompatibility. The result showed the composite scaffolds provided a favourable environment for initial cell adhesion, maintained cell viability and cell proliferation, and had good tissue compatibility.     

Microwave processing of starch‐based porous structures for tissue engineering scaffolds

A novel microwave (MW) processing technique was used to produce biodegradable scaffolds for tissue engineering from different types of starch‐based polymers. Potato, sweet potato, corn starch, and nonisolated amaranth and quinoa starch were used to produce porous structures. Water and glycerol were used as plasticizers for the different types of starch. Characterization of the pore morphology of the scaffolds was carried out with scanning electron microscopy. Three‐dimensional structures with variable porosity and pore size distribution were obtained with the MW foaming technique. The amount of remaining water in the scaffolds and their corresponding densities showed important variations among the different types of starch. Compressive mechanical properties were assessed by indentation tests, and a strong dependence of the indentation stress on the average pore size was found. Studies in simulated body fluid were used to assess the in vitro bioactivity, degradability, and surface topology evolution in the scaffolds. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1332–1339, 2007     

Effect of Viscosity on Preparation of Foamed Silica Ceramics by a Rapid Gelation Foaming Method

An environmentally benign preparation method for silica foam (the rapid gelation foaming method) was developed by combining sol-gel reactions and mechanical foaming without using organic polymers or monomers, in order to generate less CO₂ and harmful gases from the decomposition of organic compounds contained in the raw material. The viscosity of the silica sol during foaming affects the porous properties of the silica foam, i.e. the porosity and average pore size decrease with increasing viscosity. The pore structure of the silica foams depend on the viscosity of silica sol, two types of pore structure being formed. An open-pore structure is obtained by foaming low-viscosity sols, while a closed-pore structure is obtained by foaming high-viscosity sols. Since the viscosity of the silica sol affects the stability and foaming ability of the foam, the porous properties of the product can be controlled by controlling the viscosity of the silica during foaming.     

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.     

Investigation on Foam Self‐Generation Using In Situ Carbon Dioxide (CO2) for Enhancing Oil Recovery

In situ carbon dioxide (CO₂) foam flooding has proved to be economically feasible in the oil field, but its self‐generation behavior in the bulk scale/porous media is far from understood. In this study, the optimum in situ CO₂‐foaming agent was first screened, and then in situ foam was investigated in the bulk. In situ foam flooding was conducted to evaluate the displacement characteristics and enhanced oil recovery of this system. The results showed that the foaming agent comprising 0.5% sodium dodecyl sulfonate (SDS) + 0.5% lauramido propyl hydroxyl sultaine (LHSB) gave the best foam properties and that the in situ CO₂ foam with a slow releasing rate is effective both in bulk scale and in porous media, allowing a considerable enhancement of oil recovery in sand packs with different permeabilities.     

Suppressed grain growth in highly porous barium titanate foams by two‐step sintering

Porous barium titanate has gained significant attention in recent years for their potential use in applications such as scaffolds for bone tissue engineering, stress sensors, gas sensors, and many others. However, there is very little control over the grain size of the material during the sintering processes specially to achieve little or no growth of the starting powders. Here, using the two‐step sintering method barium titanate foams were shown to be synthesized with controlled grain size of the struts without significant differences in the pore structure of the materials. In order to evaluate the applicability of two‐step sintering for a variety of processing methods, highly porous (>80% porosity) foams synthesized through the direct polyurethane foaming method were used to create conditions furthest from bulk where two‐step sintering has shown success. Two‐step sintering parameters were identified and the processing conditions were confirmed to not alter the mechanical properties of the samples due to expected residual stresses or thermal shock resulting from the rapid heating and cooling rates employed.     

可注射nHA/PU复合多孔骨修复支架制备及表征

兼具良好孔隙率和原位任意塑形固化的可注射复合多孔骨修复材料在临床不规则骨缺损的治疗方面显示出巨大的优势。本研究通过优化双组分设计,以水为发泡剂制备可注射纳米羟基磷灰石/聚氨酯（nHA/PU）复合多孔支架。利用扫描电子显微镜（SEM）、傅里叶变换红外光谱（FTIR）、X射线衍射（XRD）、力学测试及Gillmore针测试等手段对制备的支架进行结构形貌、化学组成、力学性能和固化时间表征。结果表明,本研究制备的可注射nHA/PU复合多孔支架孔隙率高、孔隙贯通性好,孔径分布在100~700μm,适宜细胞和组织向孔内生长;添加20% nHA显著提高了PU支架的力学强度,但降低了支架的孔隙率;可注射支架在8h固化,适宜临床操作。本研究制备的可注射nHA/PU复合多孔支架在不规则骨缺损修复领域具有较大的应用潜力。     

Bubble behaviors in chemical direct foaming process and effects on pore structures of geopolymer foams

Geopolymer foams (GPFs) are considered potential candidates for the highly porous ceramics owing to their high porosity and simple synthesis. In this study, bubble behaviors during different phases of the foaming process and their effects on the pore structure of molded GPFs were examined. The foaming reaction characteristics in a foaming system containing H₂O₂ were adjusted based on variables, such as catalyst content, temperature, activator-to-precursor ratio, and surfactant content. The viscosity of the slurry was also measured under different experimental conditions. Bubble behaviors were determined by characterizing the change in the gas volume in the slurry and the pore structure of the molded GPFs. Different pore structures will be realized by adjusting the relationship between the extrusion effect and liquid film properties in the various foaming phases.     

Formation of closed pore structure in CaO-MgO-Al2O3-SiO2 (CMAS) porous glass-ceramics via Fe2O3 modified foaming for thermal insulation

Due to the low density, low thermal conductivity and low water absorption, porous glass-ceramics have demonstrated excellent performance for thermal insulation. Closed pore structure can greatly reduce the thermal conductivity and convection as well as achieve high mechanical strength. However, yet it is difficult to realize closed pore structure due to the critical preparation condition. Here we use Fe₂O₃, which is the by-product of copper tailings, to optimize the pores structures of the porous glass-ceramics and facilitate the formation of uniform closed pore structure. The porous glass-ceramics were prepared by melting-quenching method, followed by sufficiently foaming through powder sintering route with SiC powders as foaming agent. The foaming process, micro structure, pore structure and thermal insulation performance were directly observed by heating microscope, scanning electron microscope (SEM), X-ray computed tomography and infrared thermal imager. The results show that the addition of Fe₂O₃ modified the depolymerization degree of the glass network and increased the numbers of non-bridged oxygen, decreasing the foaming temperature. The resultant closed pore structure showed a better thermal insulating performance than open pore structure. Accordingly, we achieved a low thermal conductivity of 0.19 W·m^?1·K^?1 with the highest specific strength of 19.55 MPa·g^?1·cm^?3 based on closed pore structure.     

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     

Bi-/multi-modal pore formation of PLGA/hydroxyapatite composite scaffolds by heterogeneous nucleation in supercritical CO2 foaming

Scaffolds with multimodal pore structure are essential to cells differentiation and proliferation in bone tissue engineering.Bi-/multi-modal porous PLGA/hydroxyapatite composite scaffolds were prepared by supercritical CO_2 foaming in which hydroxyapatite acted as heterogeneous nucleation agent.Bimodal porous scaffolds were prepared under certain conditions,i.e.hydroxyapatite addition of 5%,depressurization rate of 0.3 MPa·min~(-1),soaking temperature of 55℃,and pressure of 9 MPa.And scaffolds presented specific structure of small pores(122 μm±66 μm)in the cellular walls of large pores(552μm±127μm).Furthermore,multimodal porous PLGA scaffolds with micro-pores(37 μm±11 μm)were obtained at low soaking pressure of 7.5 MPa.The interconnected porosity of scaffolds ranged from(52.53±2.69)% to(83.08±2.42)%by adjusting depressurization rate,while compression modulus satisfied the requirement of bone tissue engineering.Solvent-free CO_2 foaming method is promising to fabricate bi-/multi-modal porous scaffolds in one step,and bioactive particles for osteogenesis could serve as nucleation agents.     

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