Current Trend and New Opportunities for Multifunctional Bio-Scaffold Fabrication via High-Pressure Foaming.

Biocompatible and biodegradable foams prepared using the high-pressure foaming technique have been widely investigated in recent decades as porous scaffolds for in vitro and in vivo tissue growth. In fact, the foaming process can operate at low temperatures to load bioactive molecules and cells within the pores of the scaffold, while the density and pore architecture, and, hence, properties of the scaffold, can be finely modulated by the proper selection of materials and processing conditions. Most importantly, the high-pressure foaming of polymers is an ideal choice to limit and/or avoid the use of cytotoxic and tissue-toxic compounds during scaffold preparation. The aim of this review is to provide the reader with the state of the art and current trend in the high-pressure foaming of biomedical polymers and composites towards the design and fabrication of multifunctional scaffolds for tissue engineering. This manuscript describes the application of the gas foaming process for bio-scaffold design and fabrication and highlights some of the most interesting results on: (1) the engineering of porous scaffolds featuring biomimetic porosity to guide cell behavior and to mimic the hierarchical architecture of complex tissues, such as bone; (2) the bioactivation of the scaffolds through the incorporation of inorganic fillers and drugs.

Bubble Rupture and Bursting Velocity of Complex Fluids.

We analyzed bubble rupture and hole opening dynamics in a non-Newtonian fluid by investigating the retraction process of thin films after inflation at different blowing rates. The experiments were modeled through a dimensional analysis, with the aim of establishing a general approach on the bubble rupture dynamics and discerning the role of viscous, elastic, surface, and inertial forces on the opening velocity, according to the nature of the specific fluid. A new mathematical model, which includes all possible contributions to the hole opening dynamics, was proposed, to the best of our knowledge for the first time. The experimental evidence on the opening velocity as a function of the inflation rate was found to be in good agreement with the prediction of the model. The sensitivity of our modeling was tested by comparing our results with the existing models of retracting velocity.

Competition between CO2-philicity and Mixing Entropy Leads to CO2 Solubility Maximum in Polyether Polyols.

In carbon dioxide-blown polymer foams, the solubility of carbon dioxide (CO2) in the polymer profoundly shapes the structure and, consequently, the physical properties of the foam. One such foam is polyurethane-commonly used for thermal insulation, acoustic insulation, and cushioning-which increasingly relies on CO2 to replace environmentally harmful blowing agents. Polyurethane is produced through the reaction of isocyanate and polyol, of which the polyol has the higher capacity for dissolving CO2. While previous studies have suggested the importance of the effect of hydroxyl end groups on CO2 solubility in short polyols (<1000 g/mol), their effect in polyols with higher molecular weight (≥1000 g/mol) and higher functionality (>2 hydroxyls per chain)-as are commonly used in polyurethane foams-has not been reported. Here, we show that the solubility of CO2 in polyether polyols decreases with molecular weight above 1000 g/mol and decreases with functionality using measurements performed by gravimetry-axisymmetric drop-shape analysis. The nonmonotonic effect of molecular weight on CO2 solubility results from the competition between effects that reduce CO2 solubility (lower mixing entropy) and effects that increase CO2 solubility (lower ratio of hydroxyl end groups to ether backbone groups). To generalize our measurements, we modeled the CO2 solubility using a perturbed chain-statistical associating fluid theory (PC-SAFT) model, which we validated by showing that a density functional theory model based on the PC-SAFT free energy accurately predicted the interfacial tension.

Developing Insulating Polymeric Foams: Strategies and Research Needs from a Circular Economy Perspective.

Insulating polymeric foams have an important role to play in increasing energy efficiency and therefore contributing to combating climate change. Their development in recent years has been driven towards the reduction of thermal conductivity and achievement of the required mechanical properties as main targets towards sustainability. This perception of sustainability has overseen the choice of raw materials, which are often toxic, or has placed research efforts on optimizing one constituent while the other necessary reactants remain hazardous. The transition to the circular economy requires a holistic understanding of sustainability and a shift in design methodology and the resulting research focus. This paper identifies research needs and possible strategies for polymeric foam development compatible with Circular Product Design and Green Engineering, based on an extensive literature review. Identified research needs include material characterization of a broader spectrum of polymer melt-gas solutions, ageing behavior, tailoring of the polymer chains, detailed understanding and modeling of the effects of shear on cell nucleation, and the upscaling of processing tools allowing for high and defined pressure drop rates.

Role of Air Bubble Inclusion on Polyurethane Reaction Kinetics.

In this study, we investigated the influence of mixing conditions on the foaming process of water blown polyurethane (PU) foams obtained at different mixing speeds (50, 500, 1000 and 2000 rpm). In particular, the morphological evolution during the foaming process, in terms of the bubble size and bubble density, was studied via optical observations, while the effects on the reaction kinetics were monitored using in situ FTIR spectroscopy. At the slow mixing speed (50 rpm), no air bubbles were included and the early foaming process was characterized by the formation of new bubbles (CO2 nucleation), provided by the blowing reaction. Later on, it was observed that the coalescence affected the overall foaming process, caused by the gelling reaction, which was inhibited by the indigent mixing conditions and could not withstand the bubbles expansion. As a result, a PU foam with a coarse cellular structure and an average bubble size of 173 µm was obtained. In this case, the bubbles degeneration rate, dN/dt, was -3095 bubble·cm-3·s-1. On the contrary, at 500 rpm, air bubbles were included into the PU reaction system (aeration) and no formation of new bubbles was observed during the foaming process. After this, the air bubbles underwent growth caused by diffusion of the CO2 provided by the blowing reaction. As the gelling reaction was not strongly depleted as in the case at 50 rpm, the coalescence less affected the bubble growth (dN/dt = -2654 bubble·cm-3·s-1), leading to a PU foam with an average bubble size of 94 µm. For the foams obtained at 1000 and 2000 rpm, the bubble degeneration was first affected by coalescence and then by Ostwald ripening, and a finer cellular structure was observed (with average bubble sizes of 62 µm and 63 µm for 1000 rpm and 2000 rpm, respectively). During the first foaming stage, the coalescence was less predominant in the bubble growth (with dN/dt values of -1838 bubble·cm-3·s-1 and -1601 bubble·cm-3·s-1, respectively) compared to 50 rpm and 500 rpm. This occurrence was ascribed to the more balanced process between the bubble expansion and the PU polymerization caused by the more suitable mixing conditions. During the late foaming stage, the Ostwald ripening was only responsible for the further bubble degeneration (with dN/dt values of -89 bubble·cm-3·s-1 and -69 bubble·cm-3·s-1, respectively).

Flowering in bursting bubbles with viscoelastic interfaces.

The lifetime of bubbles, from formation to rupture, attracts attention because bubbles are often present in natural and industrial processes, and their geometry, drainage, coarsening, and rupture strongly affect those operations. Bubble rupture happens rapidly, and it may generate a cascade of small droplets or bubbles. Once a hole is nucleated within a bubble, it opens up with a variety of shapes and velocities depending on the liquid properties. A range of bubble rupture modes are reported in literature in which the reduction of a surface energy drives the rupture against inertial and viscous forces. The role of surface viscoelasticity of the liquid film in this colorful scenario is, however, still unknown. We found that the presence of interfacial viscoelasticity has a profound effect in the bubble bursting dynamics. Indeed, we observed different bubble bursting mechanisms upon the transition from viscous-controlled to surface viscoelasticity-controlled rupture. When this transition occurs, a bursting bubble resembling the blooming of a flower is observed. A simple modeling argument is proposed, leading to the prediction of the characteristic length scales and the number and shape of the bubble flower petals, thus paving the way for the control of liquid formulations with surface viscoelasticity as a key ingredient. These findings can have important implications in the study of bubble dynamics, with consequences for the numerous processes involving bubble rupture. Bubble flowering can indeed impact phenomena such as the spreading of nutrients in nature or the life of cells in bioreactors.

Classification and Production of Polymeric Foams among the Systems for Wound Treatment.

This work represents an overview on types of wounds according to their definition, classification and dressing treatments. Natural and synthetic polymeric wound dressings types have been analyzed, providing a historical overview, from ancient to modern times. Currently, there is a wide choice of materials for the treatment of wounds, such as hydrocolloids, polyurethane and alginate patches, wafers, hydrogels and semi-permeable film dressings. These systems are often loaded with drugs such as antibiotics for the simultaneous delivery of drugs to prevent or cure infections caused by the exposition of blood vessel to open air. Among the presented techniques, a focus on foams has been provided, describing the most diffused branded products and their chemical, physical, biological and mechanical properties. Conventional and high-pressure methods for the production of foams for wound dressing are also analyzed in this work, with a proposed comparison in terms of process steps, efficiency and removal of solvent residue. Case studies, in vivo tests and models have been reported to identify the real applications of the produced foams.

Modelling Sorption Thermodynamics and Mass Transport of n-Hexane in a Propylene-Ethylene Elastomer.

Optimization of post polymerization processes of polyolefin elastomers (POE) involving solvents is of considerable industrial interest. To this aim, experimental determination and theoretical interpretation of the thermodynamics and mass transport properties of POE-solvent mixtures is relevant. Sorption behavior of n-hexane vapor in a commercial propylene-ethylene elastomer (V8880 VistamaxxTM from ExxonMobil, Machelen, Belgium) is addressed here, determining experimentally the sorption isotherms at temperatures ranging from 115 to 140 °C and pressure values of n-hexane vapor up to 1 atm. Sorption isotherms have been interpreted using a Non Random Lattice Fluid (NRLF) Equation of State model retrieving, from data fitting, the value of the binary interaction parameter for the n-hexane/V8880 system. Both the cases of temperature-independent and of temperature-dependent binary interaction parameter have been considered. Sorption kinetics was also investigated at different pressures and has been interpreted using a Fick's model determining values of the mutual diffusivity as a function of temperature and of n-hexane/V8880 mixture composition. From these values, n-hexane intra-diffusion coefficient has been calculated interpreting its dependence on mixture concentration and temperature by a semi-empiric model based on free volume arguments.

Axisymmetric bare freestanding films of highly viscous liquids: Preparation and real-time investigation of capillary leveling.

HYPOTHESIS: Thin liquid films are important in many scientific fields. In particular, films with both the surface layers exposed to a different fluid phase, known as freestanding films, are relevant in the ambit of foams and emulsions. Hence, there is a great interest in developing novel techniques allowing to form large and stable freestanding liquid films and to follow their dynamics. EXPERIMENTS: We develop a novel opto-mechanical tool allowing to perform and study the preparation and the capillary leveling flow of axisymmetric bare freestanding liquid films. The tool is composed by a customized motorized iris diaphragm and by an innovative joint imaging setup combining digital holography and white light color interferometry that enables real-time measurement of film thickness over a large field of view. The dynamics of films made of a model Newtonian fluid, i.e., high-viscosity silicone oil, is studied. Direct numerical simulations and a hydrodynamic model based on the lubrication theory are used to support the experimental results. FINDINGS: Iris opening induces the formation of large circular freestanding films with a stepped profile. Once iris opening is stopped, the films undergo a capillary leveling flow tending to flatten their profile. The leveling flow follows the theoretical scaling given by Ilton et al. [1]. We prove through numerical simulations that an equi-biaxial extensional flow occurs at the film center. Furthermore, we observe the formation and dynamics of dimples in bare freestanding films for the first time.

Testing Surgical Face Masks in an Emergency Context: The Experience of Italian Laboratories during the COVID-19 Pandemic Crisis.

The first wave of the COVID-19 pandemic brought about a broader use of masks by both professionals and the general population. This resulted in a severe worldwide shortage of devices and the need to increase import and activate production of safe and effective surgical masks at the national level. In order to support the demand for testing surgical masks in the Italian context, Universities provided their contribution by setting up laboratories for testing mask performance before releasing products into the national market. This paper reports the effort of seven Italian university laboratories who set up facilities for testing face masks during the emergency period of the COVID-19 pandemic. Measurement set-ups were built, adapting the methods specified in the EN 14683:2019+AC. Data on differential pressure (DP) and bacterial filtration efficiency (BFE) of 120 masks, including different materials and designs, were collected over three months. More than 60% of the masks satisfied requirements for DP and BFE set by the standard. Masks made of nonwoven polypropylene with at least three layers (spunbonded-meltblown-spunbonded) showed the best results, ensuring both good breathability and high filtration efficiency. The majority of the masks created with alternative materials and designs did not comply with both standard requirements, resulting in suitability only as community masks. The effective partnering between universities and industries to meet a public need in an emergency context represented a fruitful example of the so-called university "third-mission".

[Validation of surgical masks during COVID19 emergency: activities at the University of Napoli Federico II]. / Validazione di maschere chirurgiche nella fase di emergenza COVID19: l'esperienza dell'Università degli Studi di Napoli Federico II.

SUMMARY: During COVID-19 pandemic crisis, Italian Government has approved Law Decree no. 18 of 17 march 2020, in which art. 15 allows enterprises to produce, import and commercialize surgical masks notwithstanding the current rules of product certification. It is just required that the interested enterprises send to the Italian National Institute of Health a selfcertification in which they declare the technical characteristics of the masks and that masks are produced according to the safety requirements. In this context, a technical-scientific unit was established at the University of Napoli Federico II to provide interested enterprises with state-of-the-art consultancy, testing and measurement services, adhering to rigorous scientific protocols. Characterization tests were carried out on 163 surgical masks and/or materials for their construction and they have enabled the identification of pre-screening criteria to simplify the procedure for evaluating surgical masks using methods for assessing the filtration efficiency of particles and aerosols. Based on experimental results, it has been observed that a filtration efficiency for particles with sizes larger that 650 nm (PFE>650) exceeding 35% might guarantees a bacterial filtration efficiency (BFE) higher than 95% while BFE values higher than 98% are obtained when the PFE>650 is larger than 40%. PFE measurement is extremely simpler with respect to BFE, the latter being time-consuming and requiring specific equipment and methods for its realization. Many tested materials have shown the capability to assure high filtration efficiencies but Spundonded-Meltblown-Spunbonded (SMS), that are layers of non-woven fabric with different weights of Meltblown, can simultaneously guarantee high particle filtration efficiencies with pressure drop values (breathability) in the limits to classify the surgical masks as Type II/IIR. In fact, the fabric products analyzed so far have not been able to simultaneously guarantee adequate BFE and breathability values. On the contrary, Spunbonds of adequate weights can virtually verify both requirements and accredit themselves as possible materials for the production of surgical masks, at least of Type I. Further studies are needed to verify the possibility of producing low-cost, reusable surgical masks that could meet the criteria of circular economy.

Tuning the three-dimensional architecture of supercritical CO2 foamed PCL scaffolds by a novel mould patterning approach.

In tissue engineering, the use of supercritical CO2 foaming is a valuable and widespread choice to design and fabricate porous bioactive scaffolds for cells culture and new tissue formation in three dimensions. Nevertheless, the control of scaffold pores size, shape and spatial distribution with foaming technique remains, to date, a critical limiting step. To mimic the biomimetic structure of tissues like bone, blood vessels and nerve tissues, we developed a novel supercritical CO2-foaming approach for the preparation of dual-scale, dual-shape porous polymeric scaffolds with pre-defined arrays of micro-channels within a foamed porosity. The scaffolds were prepared by foaming the polymer inside polytetrafluoroethylene moulds having precisely designed arrays of pillars and obtained by computer-aided micromachining technique. Polycaprolactone was chosen as model polymer for scaffolds fabrication and the effect of mould patterning and scCO2 foaming conditions on scaffolds morphology, structural properties and biocompatibility was addressed and discussed. The results reported in this study demonstrated that the proposed approach enabled the preparation of polycaprolactone scaffolds with dual-scale, dual-shape porosity. In particular, by saturating the polymer with CO2 at 38 °C, 10 MPa and 1 h and by selecting 2 s as the venting time, scaffolds with ordered arrays of aligned channels, diameters ranging from 500 to 1000 µm, were obtained. Furthermore, the channels spatial distribution was controlled by defining mould patterning while the size of foamed pores was modulated by saturation and foaming temperatures and venting time control. The prepared scaffolds evidenced overall porosity up to 95%, with 100% interconnectivity and compression moduli in the 4 to 5 MPa range. Finally, preliminary in vitro cell culture tests evidenced that the scaffolds were biocompatible and that the micro-channels promoted and guided cells adhesion and colonization into the scaffolds core.

Quantitative imaging of the complexity in liquid bubbles' evolution reveals the dynamics of film retraction.

The dynamics and stability of thin liquid films have fascinated scientists over many decades. Thin film flows are central to numerous areas of engineering, geophysics, and biophysics and occur over a wide range of lengths, velocities, and liquid property scales. In spite of many significant developments in this area, we still lack appropriate quantitative experimental tools with the spatial and temporal resolution necessary for a comprehensive study of film evolution. We propose tackling this problem with a holographic technique that combines quantitative phase imaging with a custom setup designed to form and manipulate bubbles. The results, gathered on a model aqueous polymeric solution, provide unparalleled insight into bubble dynamics through the combination of a full-field thickness estimation, three-dimensional imaging, and a fast acquisition time. The unprecedented level of detail offered by the proposed methodology will promote a deeper understanding of the underlying physics of thin film dynamics.

Elasticity in Bubble Rupture.

When a Newtonian bubble ruptures, the film retraction dynamics is controlled by the interplay of surface, inertial, and viscous forces. In case a viscoelastic liquid is considered, the scenario is enriched by the appearance of a new significant contribution, namely, the elastic force. In this paper, we investigate experimentally the retraction of viscoelastic bubbles inflated at different blowing rates, showing that the amount of elastic energy stored by the liquid film enclosing the bubble depends on the inflation history and in turn affects the velocity of film retraction when the bubble is punctured. Several viscoelastic liquids are considered. We also perform direct numerical simulations to support the experimental findings. Finally, we develop a simple heuristic model able to interpret the physical mechanism underlying the process.

Microcellular foaming of arabinoxylan and PEGylated arabinoxylan with supercritical CO2.

In this study, arabinoxylan extracted from barley husks was reacted with polyethylene glycol (PEG) of various molecular weights to introduce an internal plasticizer into the polymer matrix. A successful PEGylation reaction was identified using FTIR and elemental analysis. Thermal and mechanical properties were studied using dynamic mechanical analysis, which revealed that the attachment of PEG chains reduced the glass transition temperature by up to 25°C. Foaming experiments were conducted under different test conditions in a batch foaming process with supercritical CO2 in a thermoregulated and pressurized cylinder. The foams were evaluated using SEM by studying the morphology of the samples foamed at different temperatures. The unmodified arabinoxylan sample was found to produce the best foam morphology, though the PEGylated samples could be produced at lower temperatures than could the unmodified arabinoxylan. This was interpreted as due to the decrease in the glass transition temperature.

Raman Line Imaging of Poly(ε-caprolactone)/Carbon Dioxide Solutions at High Pressures: A Combined Experimental and Computational Study for Interpreting Intermolecular Interactions and Free-Volume Effects.

In the present study, a Raman line-imaging setup was employed to monitor in situ the CO2 sorption at elevated pressures (from 0.62 to 7.10 MPa) in molten PCL. The method allowed the quantitative measurement of gas concentration in both the time-resolved and the space-resolved modes. The combined experimental and theoretical approach allowed a molecular level characterization of the system. The dissolved CO2 was found to occupy a volume essentially coincident with its van der Waals volume and the estimated partial molar volume of the probe did not change with pressure. Lewis acid-Lewis base interactions with the PCL carbonyls was confirmed to be the main interaction mechanism. The geometry of the supramolecular complex and the preferential interaction site were controlled more by steric than electronic effects. On the basis of the indications emerging from Raman spectroscopy, an equation of state thermodynamic model for the PCL-CO2 system, based upon a compressible lattice fluid theory endowed with specific interactions, has been tailored to account for the interaction types detected spectroscopically. The predictions of the thermodynamic model in terms of molar volume of solution have been compared with available volumetric measurements while predictions for CO2 partial molar volume have been compared with the values estimated on the basis of Raman spectroscopy.

Supercritical CO2 foaming of thermoplastic materials derived from maize: proof-of-concept use in mammalian cell culture applications.

BACKGROUND: Foams are high porosity and low density materials. In nature, they are a common architecture. Some of their relevant technological applications include heat and sound insulation, lightweight materials, and tissue engineering scaffolds. Foams derived from natural polymers are particularly attractive for tissue culture due to their biodegradability and bio-compatibility. Here, the foaming potential of an extensive list of materials was assayed, including slabs elaborated from whole flour, the starch component only, or the protein fraction only of maize seeds. METHODOLOGY/PRINCIPAL FINDINGS: We used supercritical CO2 to produce foams from thermoplasticized maize derived materials. Polyethylene-glycol, sorbitol/glycerol, or urea/formamide were used as plasticizers. We report expansion ratios, porosities, average pore sizes, pore morphologies, and pore size distributions for these materials. High porosity foams were obtained from zein thermoplasticized with polyethylene glycol, and from starch thermoplasticized with urea/formamide. Zein foams had a higher porosity than starch foams (88% and 85%, respectively) and a narrower and more evenly distributed pore size. Starch foams exhibited a wider span of pore sizes and a larger average pore size than zein (208.84 vs. 55.43 µm2, respectively). Proof-of-concept cell culture experiments confirmed that mouse fibroblasts (NIH 3T3) and two different prostate cancer cell lines (22RV1, DU145) attached to and proliferated on zein foams. CONCLUSIONS/SIGNIFICANCE: We conducted screening and proof-of-concept experiments on the fabrication of foams from cereal-based bioplastics. We propose that a key indicator of foamability is the strain at break of the materials to be foamed (as calculated from stress vs. strain rate curves). Zein foams exhibit attractive properties (average pore size, pore size distribution, and porosity) for cell culture applications; we were able to establish and sustain mammalian cell cultures on zein foams for extended time periods.

Effect of supramolecular structures on thermoplastic zein-lignin bionanocomposites.

The effect of alkaline lignin (AL) and sodium lignosulfonate (LSS) on the structure of thermoplastic zein (TPZ) was studied. Protein structural changes and the nature of the physical interaction between lignin and zein were investigated by means of X-ray diffraction and Fourier transform infrared (FT-IR) spectroscopy and correlated with physical properties. Most relevant protein structural changes were observed at low AL concentration, where strong H-bondings between the functional groups of AL and the amino acids in zein induced a destructuring of inter- and intramolecular interactions in α-helix, ß-sheet, and ß-turn secondary structures. This destructuring allowed for an extensive protein conformational modification which, in turn, resulted in a strong improvement of the physical properties of the bionanocomposite.

Design of bimodal PCL and PCL-HA nanocomposite scaffolds by two step depressurization during solid-state supercritical CO(2) foaming.

This communication reports the design and fabrication of porous scaffolds of poly(ε-caprolactone) (PCL) and PCL loaded with hydroxyapatite (HA) nanoparticles with bimodal pore size distributions by a two step depressurization solid-state supercritical CO(2) (scCO(2) ) foaming process. Results show that the pore structure features of the scaffolds are strongly affected by the thermal history of the starting polymeric materials and by the depressurization profile. In particular, PCL and PCL-HA nanocomposite scaffolds with bimodal and uniform pore size distributions are fabricated by quenching molten samples in liquid N(2) , solubilizing the scCO(2) at 37 °C and 20 MPa, and further releasing the blowing agent in two steps: (1) from 20 to 10 MPa at a slow depressurization rate, and (2) from 10 MPa to the ambient pressure at a fast depressurization rate. The biocompatibility of the bimodal scaffolds is finally evaluated by the in vitro culture of human mesenchymal stem cells (MSCs), in order to assess their potential for tissue engineering applications.

Design of novel three-phase PCL/TZ-HA biomaterials for use in bone regeneration applications.

The design of bioactive scaffold materials able to guide cellular processes involved in new-tissue genesis is key determinant in bone tissue engineering. The aim of this study was the design and characterization of novel multi-phase biomaterials to be processed for the fabrication of 3D porous scaffolds able to provide a temporary biocompatible substrate for mesenchymal stem cells (MSCs) adhesion, proliferation and osteogenic differentiation. The biomaterials were prepared by blending poly(epsilon-caprolactone) (PCL) with thermoplastic zein (TZ), a thermoplastic material obtained by de novo thermoplasticization of zein. Furthermore, to bioactivate the scaffolds, microparticles of osteoconductive hydroxyapatite (HA) were dispersed within the organic phases. Results demonstrated that materials and formulations strongly affected the micro-structural properties and hydrophilicity of the scaffolds and, therefore, had a pivotal role in guiding cell/scaffold interaction. In particular, if compared to neat PCL, PCL-HA composite and PCL/TZ blend, the three-phase PCL/TZ-HA showed improved MSCs adhesion, proliferation and osteogenic differentiation capability, thus demonstrating potential for bone regeneration.