Solvent-free Fabrication Research Articles

Solvent-free fabrication of thermally conductive insulating epoxy composites with boron nitride nanoplatelets as fillers.

A solvent-free method for the fabrication of thermally conductive epoxy-boron nitride (BN) nanoplatelet composite material is developed in this study. By this method, polymer composites with nearly any filler fractions can be easily fabricated. The maximum thermal conductivity reaches 5.24 W/mK, which is 1,600% improvement in comparison with that of pristine epoxy material. In addition, the as-fabricated samples exhibit excellent overall performances with great mechanical property and thermal stability well preserved.

Solvent free production of porous PDLLA/calcium carbonate composite scaffolds improves the release of bone growth factors.

Incorporation of alkaline nano-/microparticles for neutralization of acidic degradation products into degradable polymer foams requires the use of organic solvents, which may compromise biocompatibility and may be associated with biological hazards. The aim of the present study was to develop and validate a solvent-free method to produce porous poly (DL-lactic acid)/calcium carbonate composite scaffolds (PDLLA/CaCO3) for controlled release of incorporated osteogenic growth factors. Composite PDLLA/CaCO3 granules were produced using a milling process and compared to composite material fabricated through a solution precipitation process using organic solvents. Particle size and mineral content were comparable in both groups. Supercritical carbon dioxide pressure was used to incorporate rhBMP2 into both composites. Gas foaming resulted in comparable pore structures in both groupsexhibiting a homogenous distribution of CaCO3 microparticles in the polymer scaffolds. The elasticity modulus of both types of scaffolds was not significantly different whereas the bending strength of the solvent-free produced scaffolds was significantly lower. The pH values remained constant between 6.90 and 7.25 during degradation of both composites. Release of BMP2 was significantly higher and the induction of alkaline phosphatase was more reliable in the group of scaffolds produced without organic solvents. Solvent-free fabrication of composite PDLLA/CaCO3 scaffolds for controlled release of bone growth factors through gas foaming significantly enhances the release of growth factors and improves the biological efficacy of the incorporated growth factors.

Solvent-free fabrication of polyHIPE microspheres for controlled release of growth factors.

The growth factor bone morphogenetic protein 2 (BMP-2) is utilized in surgical procedures to improve bone regeneration; however, current treatments deliver BMP-2 at amounts greater than 100,000 fold of physiological levels, which increases treatment costs and risk of side effects. Drug-eluting microcarriers developed to improve these therapies have faced significant commercialization challenges including particle size distributions, solvent removal, low encapsulation efficiency, and bioactivity loss. In this study, a solvent-free method is presented for fabrication of uniform polyHIPE microspheres for controlled growth factor release. Emulsion templating principles and fluid dynamics were used to fabricate uniform particles with tunable particle size (200-800 μm) and pore size (10-30 μm). The ability to independently tune particle and pore size is expected to provide excellent control of release kinetics. Overall, this solvent-free method for making porous microspheres displays strong promise for the controlled release of BMP-2 and other growth factors.

Solvent-Free Fabrication of Tissue Engineering Scaffolds With Immiscible Polymer Blends

A completely organic solvent-free fabrication method is developed for tissue engineering scaffolds by gas foaming of immiscible polylactic acid (PLA) and sucrose blends, followed by water leaching. PLA scaffolds with above 90% porosity and 25–200 µm pore size were fabricated. The pore size and porosity was controlled with process parameters including extrusion temperature and foaming process parameters. Dynamic mechanical analysis showed that the extrusion temperature could be used to control the scaffold strength. Both unfoamed and foamed scaffolds were used to culture glioblastoma (GBM) cells M059 K. The results showed that the cells grew better in the foamed PLA scaffolds. The method presented in the paper is versatile and can be used to fabricate tissue engineering scaffolds without any residual organic solvents.

Solvent‐Free Directed Patterning of a Highly Ordered Liquid Crystalline Organic Semiconductor via Template‐Assisted Self‐Assembly for Organic Transistors

Highly ordered organic semiconductor micropatterns of the liquid-crystalline small molecule 2,7-didecylbenzothienobenzothiophene (C10 -BTBT) are fabricated using a simple method based on template-assisted self-assembly (TASA). The liquid crystallinity of C10 -BTBT allows solvent-free fabrication of high-performance printed organic field-effect transistors (OFETs).

Size-controlled conformal nanofabrication of biotemplated three-dimensional TiO2 and ZnO nanonetworks

A solvent-free fabrication of TiO2 and ZnO nanonetworks is demonstrated by using supramolecular nanotemplates with high coating conformity, uniformity, and atomic scale size control. Deposition of TiO2 and ZnO on three-dimensional nanofibrous network template is accomplished. Ultrafine control over nanotube diameter allows robust and systematic evaluation of the electrochemical properties of TiO2 and ZnO nanonetworks in terms of size-function relationship. We observe hypsochromic shift in UV absorbance maxima correlated with decrease in wall thickness of the nanotubes. Photocatalytic activities of anatase TiO2 and hexagonal wurtzite ZnO nanonetworks are found to be dependent on both the wall thickness and total surface area per unit of mass. Wall thickness has effect on photoexcitation properties of both TiO2 and ZnO due to band gap energies and total surface area per unit of mass. The present work is a successful example that concentrates on nanofabrication of intact three-dimensional semiconductor nanonetworks with controlled band gap energies.

Foaming of PCL/clay nanocomposites with supercritical CO2 mixtures: The effect of nanocomposite fabrication route on the clay dispersion and the final porous structure

Supercritical fluids have been established as alternative foaming agents in various polymers as well as nanocomposite systems. Most recently, supercritical carbon dioxide (scCO2) has also been used in some studies as a medium of clay dispersion in the polymer matrix providing a solvent-free fabrication route for nanocomposites. In this work, this latter route was followed for the development of porous poly(ɿ-caprolactone) (PCL)/clay nanocomposites after pressure quench. Similarly, PCL/clay nanocomposites were also prepared using the solvent casting and melt blending methods and were then processed with scCO2 with the batch foaming technique (isothermal pressure quench) to produce their porous counterparts. Poor clay dispersion and non-uniform porous structures were observed when pure CO2 was used as a dispersion medium for nanocomposite preparation and as a blowing agent, respectively. On the contrary, polymer intercalation and more uniform cell structures were produced when CO2⿿ethanol mixtures were used as blowing agents.

Solvent Free Fabrication of Micro and Nanostructured Drug Coatings by Thermal Evaporation for Controlled Release and Increased Effects

Nanostructuring of drug delivery systems offers many promising applications like precise control of dissolution and release kinetics, enhanced activities, flexibility in terms of surface coatings, integration into implants, designing the appropriate scaffolds or even integrating into microelectronic chips etc. for different desired applications. In general such kind of structuring is difficult due to unintentional mixing of chemical solvents used during drug formulations. We demonstrate here the successful solvent-free fabrication of micro-nanostructured pharmaceutical molecules by simple thermal evaporation (TE). The evaporation of drug molecules and their emission to a specific surface under vacuum led to controlled assembling of the molecules from vapour phase to solid phase. The most important aspects of thermal evaporation technique are: solvent-free, precise control of size, possibility of fabricating multilayer/hybrid, and free choice of substrates. This could be shown for twenty eight pharmaceutical substances of different chemical structures which were evaporated on surfaces of titanium and glass discs. Structural investigations of different TE fabricated drugs were performed by atomic force microscopy, scanning electron microscopy and Raman spectroscopy which revealed that these drug substances preserve their structurality after evaporation. Titanium discs coated with antimicrobial substances by thermal evaporation were subjected to tests for antibacterial or antifungal activities, respectively. A significant increase in their antimicrobial activity was observed in zones of inhibition tests compared to controls of the diluted substances on the discs made of paper for filtration. With thermal evaporation, we have successfully synthesized solvent-free nanostructured drug delivery systems in form of multilayer structures and in hybrid drug complexes respectively. Analyses of these substances consolidated that thermal evaporation opens up the possibility to convert dissoluble drug substances into the active forms by their transfer onto a specific surface without the need of their prior dissolution.

Solvent-free fabrication of three dimensionally aligned polycaprolactone microfibers for engineering of anisotropic tissues

Fabrication of aligned microfiber scaffolds is critical in successful engineering of anisotropic tissues such as tendon, ligaments and nerves. Conventionally, aligned microfiber scaffolds are two dimensional and predominantly fabricated by electrospinning which is solvent dependent. In this paper, we report a novel technique, named microfiber melt drawing, to fabricate a bundle of three dimensionally aligned polycaprolactone microfibers without using any organic solvent. This technique is simple yet effective. It has been demonstrated that polycaprolactone microfibers of 10μm fiber diameter can be directly drawn from a 2mm orifice. Orifice diameter, temperature and take-up speed significantly influence the final linear density and fiber diameter of the microfibers. Mechanical test suggests that mechanical properties such as stiffness and breaking force of microfiber bundles can be easily adjusted by the number of fibers. In vitro study shows that these microfibers are able to support the proliferation of human dermal fibroblasts over 7days. In vivo result of Achilles tendon repair in a rabbit model shows that the microfibers were highly infiltrated by tendon tissue as early as in 1month, besides, the repaired tendon have a well-aligned tissue structure under the guidance of aligned microfibers. However whether these three dimensionally aligned microfibers can induce three dimensionally aligned cells remains inconclusive.

Preparation of poly(ε-caprolactone)-based tissue engineering scaffolds by stereolithography

A photocrosslinkable poly(ε-caprolactone) (PCL)-based resin was developed and applied using stereolithography. No additional solvents were required during the structure preparation process. Three-armed PCL oligomers of varying molecular weights were synthesized, functionalized with methacrylic anhydride, and photocrosslinked, resulting in high gel content networks. Stereolithography was used to build designed porous scaffolds using the resin containing PCL macromer, Irgacure 369 photoinitiator, inhibitor and dye. A suitable resin viscosity was obtained by heating the resin during the curing process. The scaffolds precisely matched the computer-aided designs, with no observable material shrinkage. The average porosity was 70.5 ± 0.8%, and the average pore size was 465 μm. The pore network was highly interconnected. The photocrosslinkable, biodegradable PCL resin is well suited for the solvent-free fabrication of tissue engineering scaffolds by stereolithography.

Biocompatibility and Mesenchymal Stem Cell Response to Poly(ɛ-Caprolactone) Nanowire Surfaces for Orthopedic Tissue Engineering

Concerns over utilizing autogenous cancellous bone grafts (such as donor-site morbidity, increased surgical time/complication rate, and restricted availability) as the gold-standard treatment for critical-sized defects in bone have motivated the development of a wide variety of sophisticated synthetic bone scaffolds in recent years. In this work, a novel solvent-free template synthesis technique was utilized to fabricate poly(epsilon-caprolactone) (PCL) nanowire surfaces as a building block for the development of three-dimensional bone scaffolds. Bone marrow-derived mesenchymal stem cells (MSCs) were used to characterize the short- and long-term in vitro biocompatibility and cellular response to these surfaces. A 4-week study in rats was conducted to assess in vivo biocompatibility as well. Short-term in vitro studies revealed that PCL nanowire surfaces enhanced MSC response in terms of survivability, viability, cytoskeleton changes, and morphology as compared with control surfaces (smooth PCL and polystyrene). In long-term in vitro studies, nanowire surfaces induced a rapid production of bone extracellular matrix by differentiated MSCs as indicated by accelerated calcium phosphate mineralization, and osteocalcin and osteopontin production. In vivo studies and histological analysis confirmed that nanowire surfaces are biocompatible. Preliminary biodegradation studies were conducted and indicated that rate of PCL biodegradation can, to some extent, be controlled through the inclusion of nanowires and ester-degrading enzymes. In addition to demonstrating enhanced short- and long-term MSC response to PCL nanowire surfaces, this work presents a simple technique for solvent-free fabrication and bioactive molecule encapsulation of biocompatible, biodegradable three-dimensional bone scaffold components and warrants further investigation.

A method for solvent-free fabrication of porous polymer using solid-state foaming and ultrasound for tissue engineering applications

Most of the existing fabrication techniques for tissue engineering scaffolds require the use of organic solvents that may never be fully removed even after long leaching hours. The residues of these organic solvents reduce the ability of biological cells to form new tissue. This paper presents an approach toward solvent-free fabrication of tissue engineering scaffolds. Interconnected porous structures were created using solid-state foaming and ultrasound. The material used in this study was polylactic acid (PLA) and the blowing agent was CO 2. In order to determine suitable process conditions, saturation and foaming studies were first conducted. Selected foam samples were then processed using pulsed ultrasound. The microstructures before and after the ultrasound processing were compared. It was shown that the inter-pore connectivity of the solid-state foams was substantially enhanced. The combined solid-state foaming and ultrasound processing provide a way to fabricate porous polymer for potential tissue engineering applications.

Solvent-free fabrication of micro-porous polyurethane amide and polyurethane-urea scaffolds for repair and replacement of the knee-joint meniscus

New porous polyurethane urea and polyurethane amide scaffolds for meniscal reconstruction have been developed in a solvent-free process. As soft segments, copolymers of 50/50 l-lactide/ ε-caprolactone have been used. After terminating the soft segment with diisocyanates, chain extension was performed with adipic acid and water. Reaction between the isocyanate groups and adipic acid or water provides carbon dioxide and results in a porous polymer. Extra hydroxyl-terminated prepolymer was added in order to regulate the amount of carbon dioxide formed in the foaming reaction. Furthermore, salt crystals ranging in size from 150 to 355 μm were added in order to induce macroporosity. The pore size was regulated by addition of surfactant and by the use of ultrasonic waves. The resulting porous polymer scaffolds exhibit good mechanical properties like a high-compression modulus of 150 kPa. Chain extension with adipic acid results in better mechanical properties due to better defined hard segments. This results from the lower nucleophilicity of carboxylic acids compared to water and alcohols. By adjusting the reaction conditions, materials in which macropores are interconnected by micropores can be obtained. On degradation only non-toxic products will be released; importantly, the materials were obtained by a simple, reproducible and solvent-free procedure.