Polycaprolactone Membrane Research Articles

Preliminary Investigation of a Sacrificial Process for Fabrication of Polymer Membranes with Sub-Micron Thickness

ABSTRACTHere we present a single mask sacrificial molding process that allows ultrathin 2-dimensional membranes to be fabricated using biocompatible polymeric materials. For initial investigations, polycaprolactone (PCL) was chosen as a model material. The process is capable of creating 250-500 nm thin, through-hole PCL membranes with various geometries, pore-sizes and spatial features approaching 2.5 micrometers using contact photolithography. The technique uses a mold created from two layers of lift-off resist (LOR). The upper layer is patterned, while the lower layer acts as a sacrificial release layer for the polymer membrane. For mold fabrication, photoresist on top of the layers of lift-off resist is patterned using conventional photolithography. During development the mask pattern is transferred onto the first LOR layer and the photoresist is removed using acetone, leaving behind a thin mold. The mold is filled with a solution of the desired polymer. Subsequently, both the patterned and lower LOR layers are dissolved by immersion in an alkaline solution. The membrane can be mounted onto support structures pre-release to facilitate handling.

Silica coating of the pore walls of a microporous polycaprolactone membrane to be used in bone tissue engineering

Polycaprolactone/silica microporous hybrid membranes were produced in two steps: A microporous polycaprolactone membrane with an interconnected porosity of 80% was obtained via a freeze extraction procedure, then silica was formed by a sol-gel reaction inside the micropores using tetraethyl orthosilicate, TEOS, as silica precursor. It is shown that silica forms a thin coating layer homogeneously distributed over the pore walls when sol-gel reaction is catalyzed by hydrochloric acid, while it forms submicron spherical particles when using basic catalyzer. Some physical properties and the viability and osteoblastic differentiation of bone marrow rat mesenchymal stem cells cultured on pure and hybrid membranes were studied.

Nanofibers Implant Functionalized by Neural Growth Factor as a Strategy to Innervate a Bioengineered Tooth

Current strategies for jaw reconstruction require multiple procedures, to repair the bone defect, to offer sufficient support, and to place the tooth implant. The entire procedure can be painful and time-consuming, and the desired functional repair can be achieved only when both steps are successful. The ability to engineer combined tooth and bone constructs, which would grow in a coordinated fashion with the surrounding tissues, could potentially improve the clinical outcomes and also reduce patient suffering. A unique nanofibrous and active implant for bone-tooth unit regeneration and also the innervation of this bioengineered tooth are demonstrated. A nanofibrous polycaprolactone membrane is functionalized with neural growth factor, along with dental germ, and tooth innervation follows. Such innervation allows complete functionality and tissue homeostasis of the tooth, such as dentinal sensitivity, odontoblast function, masticatory forces, and blood flow.

Silica coating of the pore walls of a microporous polycaprolactone membrane to be used in bone tissue engineering

Silica coating of the pore walls of a microporous polycaprolactone membrane to be used in bone tissue engineering

Fibro‐porous polycaprolactone membrane containing extracts of Biophytum sensitivum: A prospective antibacterial wound dressing

AbstractA fibro‐porous wound dressing with antibacterial activity was fabricated from polycaprolactone (PCL) solution containing crude extract of biophytum sensitivum (BS) a potential antibacterial herbal drug. Scanning electron microscopy revealed the smooth fibrous morphology of the PCL membrane, whereas the drug‐loaded PCL formed fibers with more interconnective junctions with an average fiber diameter between 1 and 3 μm. Physical characterization of the membrane revealed that it has excellent mechanical stability, water vapor transmission rate and that it promotes water uptake. The release characteristics by total immersion method in phosphate buffer and acetate buffer displayed an increase in drug release with time. Finally, the antibacterial activity of the membrane was tested against standard strains of Staphylococcus aureus and Escherichia coli. PCL membranes loaded with the drug extracts were able to inhibit the growth of bacterial strains which indicated that this fibro‐porous membrane could act as a potential wound‐dressing material to treat various wounds. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013

Chitosan and polycaprolactone membranes patterned via electrospinning: Effect of underlying chemistry and pattern characteristics on epithelial/fibroblastic cell behavior

Electrospinning was used as an effective route to pattern chitosan (CS) and polycaprolactone (PCL) membranes with submicron fibers having different chemical structure (PCL or PCL/collagen) and physical characteristics (size: between ≈200 and 550 nm; randomly oriented or aligned form). While the PCL fibers with diameters in the same range (≈200 nm) were patterned on both of CS and PCL membranes to evaluate the influence of the underlying membrane chemistry, only CS membranes were patterned with PCL fibers having different sizes simply by changing the electrospinning conditions to investigate the effects of pattern characteristics. Furthermore, collagen was added to the PCL fiber structure to change the chemical composition of the fibers in a cell-attractive way. Two cell lines with different morphologies, fibroblastic MC3T3-E1 preosteoblasts and epithelial Madine Darby Bovine Kidney (MDBK) cells, were cultured on the patterned membranes. The observation of cellular behavior in terms of cell morphology and F-actin synthesis was realized by scanning electron microscopy and confocal microscopy analysis during the first 12 h of culture period. The viability of cells was controlled by MTT assay through 96 h of cell culture. The cell culture studies indicated that the leading aspect for the morphology change on patterned membranes was the fiber orientation. The aligned topography controlled the morphology of cells both on CS and PCL membranes. In the presence of collagen in the fiber structure, F-actin filament synthesis increased for MC3T3-E1 and MDBK cell lines.

Integrating sol–gel with cold plasmas modified porous polycaprolactone membranes for the drug-release of silver-sulfadiazine and ketoprofen

A controlled release system composed of surface modified porous polycaprolactone (PCL) membranes combined with a layer of tetraorthosilicate (TEOS)–chitosan sol–gel was reported in this study. PCL is a hydrophobic, semi-crystalline, and biodegradable polymer with a relatively slow degradation rate. The drugs chosen for release experiments were silver-sulfadiazine (AgSD) and ketoprofen which were impregnated in the TEOS–chitosan sol–gel. The surface modification was achieved by O2 plasma and the surfaces were characterized by water contact angle (WCA) measurements, atomic force microscope (AFM), scanning electron microscope and electron spectroscopy for chemical analysis (ESCA). The results showed that the release of AgSD on O2 plasma treated porous PCL membranes was prolonged when compared with the pristine sample. On the contrary, the release rate of ketoprofen revealed no significant difference on pristine and plasma treated PCL membranes. The prepared PCL membranes showed good biocompatibility for the wound dressing biomaterial applications.

Preparation of stimuli responsive polycaprolactone membranes of controllable porous morphology via combined atom transfer radical polymerization, ring-opening polymerization and thiol–yne click chemistry

Linear di-block copolymers of poly(N-isopropylacrylamide) (PNIPAM) with a center disulfide linkage were prepared by atom transfer radical polymerization (ATRP) of N-isopropylacrylamide (NIPAM) using a bifunctional disulfide-based initiator. The center disulfide bond was cleaved by reduction with excess DL-1,4-dithiothreitol (DTT) to form thiols. The resulting thiol-terminated PNIPAM chains were conjugated to alkyne-terminated poly(e-caprolactone) (PCL) via UV-initiated thiol–yne click reaction to produce the PCL-click-PNIPAM AB2-type copolymers. The PCL-click-PNIPAM copolymers were cast by phase inversion in an aqueous medium into microporous membranes of well-defined and uniform pores. The PNIPAM content in the PCL-click-PNIPAM copolymers could be used to control the pore size and porosity of the resulting membranes. The PCL-click-PNIPAM-b-PNaSS membrane was prepared via surface-initiated ATRP of sodium 4-styrenesulfonate (NaSS) from the PCL-click-PNIPAM membrane and pore surfaces. The temperature and electrolyte responsive characteristics of the PCL-click-PNIPAM and PCL-click-PNIPAM-b-PNaSS membranes were illustrated in the swelling behavior and controlled glucose transport through the membranes. These stimuli responsive membranes with controllable morphology and low cytotoxicity have potential applications in biomedical engineering, drug delivery and tissue engineering.

Function of Poly (lactic-co-glycolic acid) Nanofiber in Reduction of Adhesion Bands

In this study, we investigated the anti-adhesive and anti-inflammatory effects of electrospun nanofibrous membranes made of polycaprolactone (PCL), poly-L-lactide (PLLA), poly (lactic-co-glycolic acid) (PLGA), and polyethersulfune (PES) in comparison with the oxidized-regenerated cellulose (Interceed). Using an adhesion induction model in mice, the membranes were sutured between the abdominal wall and peritoneum after surgical operation to reveal the best membrane for prevention of postoperative adhesion bands using two scoring adhesion systems. Compared with other membranes, PLGA, PCL, and Interceed membranes showed a greater ability to reduce adhesions. The lowest level of inflammation in adhesive tissues as well as cell attachment invitro was detected for PLGA nanofibrous membranes. These results suggested that in considering the FDA approved polymers, nanofibrous membranes prepared from PLGA exhibited the highest efficacy for the prevention of postoperative adhesion bands and hold promising potential for application as a new anti-adhesive agent.

Characterization of chitosan and polycaprolactone membranes designed for wound repair application

Polycaprolactone (PCL) and chitosan (Ch) are nontoxic, biocompatible, and biodegradable polymers of vast interest for wound repair. The aim of this work was to prepare Ch/PCL membranes in different proportions (90:10 and 80:20 w/w) in the presence and absence of the surfactant Pluronic F68 (PF68). The membranes were evaluated regarding morphology, thermal behavior, and viscoelastic properties. Sample swelling and degradation in phosphate-buffered saline (PBS), simulated body fluid (SBF), and fetal bovine serum (FBS) were determined by differential scanning calorimetry (DSC) and dynamical mechanical analysis (DMA), while cell toxicity to L929 and Vero fibroblasts was evaluated using the MTT reduction assay and cell proliferation, by DNA quantification and confocal laser microscopy. After 60 days in SBF, marked Ch matrix loss and advanced degradation of PCL particles were noticed by scanning electron microscopy (SEM). No significant differences in melting temperature (T m) and enthalpy (ΔH m) were detected by DSC. However, the surfactant increased the ΔH m. After 30 days, the membranes obtained in the presence of PF68 had absorbed more blood serum and were more degraded after exposure to simulated blood fluid for 30 days. All membranes had low cytotoxicity, and higher cell proliferation was noticed for samples obtained in the presence of the surfactant. In conclusion, the Ch/PCL membranes showed satisfactory degradability and biocompatibility, which enhances their potential for application in wound repair.

Performance of Surface-Modified Polycaprolactone on Growth Factor Binding, Release, and Proliferation of Smooth Muscle Cells

This study investigates the performance of surface modification of polycaprolactone (PCL) membrane on the binding and release behavior of basic fibroblast growth factor (bFGF) for in vitro proliferation of porcine eosophageal smooth muscle cells (PESMCs). The PCL membrane surfaces were treated using UV/ozone and the surface modified PCL was characterized using water contact angle measurement, X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) spectroscopy. The immobilization of bFGFs on the treated and non-treated PCL surfaces was also investigated using atomic force microscopy (AFM). It was found that the growth factor uptake on the PCL membrane was increased about 2-fold after treatment, which was attributed to significant contribution of oxygen containing polar groups resulting from UV/ozone treatment. Compared to non-treated PCL the treated PCL showed a prolonged bFGF release indicated by a linear increase over the first 3 days followed by a moderate and slow release profile. Moreover, the proliferation assay of PESMCs revealed that bFGF released from treated PCL had significantly higher proliferation than that of untreated PCL film. Thus, the UV/ozone-treated PCL membranes immobilized with bFGF accelerate the proliferation of PESMCs and may play an important role in soft tissue engineering.

Femtosecond laser machining of electrospun membranes

We demonstrate that a femtosecond laser can be used to machine arbitrary patterns and pattern arrays into free-standing electrospun polycaprolactone (PCL) membranes. We also examine the influence of various laser irradiation settings on the final microstructure of electrospun membranes. A beam fluence of 0.6J/cm2 is used to ablate holes in 100μm thick PCL membranes. The machined holes have an average diameter of 436μm and a center-to-center spacing of 1000μm. Based on these results, the femtosecond ablation of electrospun membranes shows great potential for fabricating a variety of functional tissue scaffolds. This technique will advance scaffold design by providing the ability to rapidly tailor surface morphology, while minimizing and controlling the deformation of the electrospun fibers.

Surface Modification of Nanoporous Poly(ϵ-caprolactone) Membrane with Poly(ethylene glycol) to Prevent Biofouling: Part I. Effects of Plasma Power and Treatment Time

Biofouling, a result of protein adsorption and cell adhesion on a surface, is detrimental to membrane performance. The objective of this study is to modify the polycaprolactone (PCL) membrane surface with poly(ethylene glycol) (PEG) to prevent fibroblast adhesion. To achieve this goal, oxygen plasma and PEG(400)-monoacrylate were used to graft the PEG onto the membrane surface through covalent bonding. Various plasma treatment conditions were investigated to optimize the PEG-grafting quality and to achieve minimum fibroblast adhesion. After the treatment, the water contact angle decreased significantly. Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) spectra indicated that PEG was successfully grafted onto the PCL membrane with the appearance of the PEG characteristic peaks. X-ray photoelectron spectroscopy (XPS) revealed that different plasma powers and treatment times changed the surface composition of membranes. To evaluate the applicability of this new strategy for the prevention of biofouling, NIH 3T3 fibroblast was used as a model biofoulant. Cell adhesion and morphology studies indicate that either lower plasma power or shorter treatment time is able to improve resistance to the cell adhesion. This simple and efficient method can be applied to inhibit biofouling on the membrane surface.

Synthesis and characterization of nanoporous polycaprolactone membranes via thermally- and nonsolvent-induced phase separations for biomedical device application

A constant and well-controlled drug release rate is of paramount importance to implantable drug delivery systems in finding the remedy against chronic diseases. This paper describes the synthesis and potential application of nanoporous poly(caprolactone) (PCL) membranes to achieve the zero-order release rate. Nanoporous PCL membranes were prepared via the combination of thermally- and nonsolvent-induced phase separations. In the membrane preparation, 1,4-dioxane and 2-methoxyethanol were used as solvent and nonsolvent, respectively, resulting in uniform nanoporous membranes and consistent lysozyme diffusion using a Teflon plate for membrane casting. Pore connectivity was improved significantly when coagulation bath temperature was lowered from 35 to 5 °C. By using a 5 °C water coagulation bath in the wet-process precipitation, the average pore size reduced from about 90 to 55 nm while increasing the casting solution concentration from 15 to 25 wt% PCL. Thus, by varying the polymer concentration of the casting solution, the lysozyme release rate was well controlled. The potential of nanoporous PCL membranes for an implantable drug delivery device to achieve the zero-order release rate was demonstrated in this study.

Peripheral Nerve Regeneration through Biodegradable Conduits Prepared Using Solvent Evaporation

The present study explored a new approach to the production of tubular conduits designed for peripheral nerve repair. Poly(L-lactic acid) (PLLA) and polycaprolactone (PCL) membranes were obtained after solvent evaporation and wrapped around a mandrel. The effectiveness of nerve regeneration was compared with that obtained with polyethylene and PCL extruded prostheses 30 and 60 days after surgery. The comparison between extruded and membrane-derived tubes clearly showed structural differences that were directly proportional to the hardness and transparency. An important factor to be considered is that the fiber count indicated that membrane-derived PCL tubes provided a significantly greater number of axons 30 days after repair. Sixty days after the procedure, the greatest regenerative performance was obtained with PCL, regardless of tube construction method. An intense imunolabeling of S100, type IV collagen, and laminin could be observed in the tissue obtained from membrane-derived PCL and PLLA groups, indicating that such constructs were able to positively stimulate Schwann cell responses. Overall, the results provided evidence that membrane-derived conduits are an alternative preparation method for tubular prostheses for peripheral nerve regeneration.

Porous membranes of PLLA–PCL blend for tissue engineering applications

Porous membranes of polycaprolactone–poly( l-lactic acid) blends were prepared by a freeze-extraction process. This procedure was able to disperse homogeneously both components despite their amorphous phases being immiscible (as proven by the fact that the glass transition temperature of PCL in the blend is independent of blend composition) and both polymers crystallize. Thus, the porous membrane consists of amorphous and crystalline phases of both components. DSC and AFM were used to characterize the microstructure of the blends, whereas SEM and gravimetric methods enabled the porosity (around 70%) and pore architecture to be determined. Compression stress–strain experiments show the characteristic behaviour of porous materials with a yield stress that rapidly drops when the PCL content increases – whereas the deformation plateau zone enlarges.

Surface modification of polycaprolactone membrane via layer‐by‐layer deposition for promoting blood compatibility

The polycaprolactone (PCL) membranes were successfully modified by deposition of chitosan/heparin multilayer via a simple electrostatic self-assembly method. To immobilize chitosan, a novel ternary polysaccharide derivate, chitosan-g-PCL-b-poly-(ethylene glycol) (PEG) was used coating on PCL film first, which resulted in the presence of positive charges onto PCL surface as the basis for following electrostatic self-assembly. The process of modification was monitored by X-ray photoelectron spectroscopy, static contact angle measurement, and atomic force microscopy. The chitosan-g-PCL-b-PEG/heparin complex immobilized on PCL surface presented it with increasing hydrophilicity and microphase separation structure. Then in vitro hemocompability experiments indicated that this multilayer deposition on PCL resisted the platelets adhesion and prolonged the plasma recalcification time effectively, relative to the untreated PCL. Such chitosan-g-PCL-b-PEG/heparin-modified PCL may have good potential for use in vascular tissue engineering.

Silver-Plated Electrospun Fibrous Anode for Glucose Alkaline Fuel Cells

This investigation is part of an effort to develop a low cost glucose-fueled fuel cell for portable devices. Electrospinning, a method that can produce high surface-to-volume ratio membranes, was used to fabricate micrometer-size polycaprolactone (PCL) fibrous electrocatalytic anode membranes for the oxidation of glucose in an alkaline fuel cell. The membranes were coated with silver using the electroless plating method that covered the whole surface of the fibers and gave the mat electrical conductivity and catalytic capability to oxidize glucose. The plated PCL membranes served as anodes in a fuel cell supplied with glucose and KOH electrolyte. With a mean plated fiber diameter membrane, the cell produced an open circuit voltage (OCV) of and a peak power density of . For a fiber membrane, the OCV was and the was . For comparison, a pure silver foil anode was placed in the same cell under the same conditions. In this case the OCV was and the reached . The experimental results indicate that the electrical performance of the fuel cell is proportional to the surface area of the fibrous anodes.

Artificial extracellular matrix proteins contain heparin‐binding and RGD‐containing domains to improve osteoblast‐like cell attachment and growth

Through the recombinant DNA technology, it is possible to create artificial extracellular matrix (aECM) proteins with domains chosen to modulate cellular behaviors. In this study, we constructed three aECM proteins containing both heparin-binding and RGD-containing domains (387RGDS, Tri-FN10, and TNC-FN3) produced in Escherichia coli. Promotion of MG-63 cell attachment and growth in two-dimensional (2D) cultures (tissue culture plate, polycaprolactone membrane) and 3D cultures (Cytodex 1 and Plastic Plus microcarriers) were demonstrated on these three aECM protein-coated surfaces. These three aECM proteins improved MG-63 cell attachment and growth in the order TNC-FN3 > Tri-FN10 > 387RGDS in both 2D and 3D cultures. This study is the first report of the construction of aECM proteins that contain both heparin-binding and RGD-containing domains used in osteoblast tissue engineering applications.

Effect of stiffness of polycaprolactone (PCL) membrane on cell proliferation

Polycaprolactone (PCL) has been fabricated into ultra thin membranes (5 ± 0.01 μm to 30 ± 0.01 μm) for tissue engineering applications by biaxial stretching. However, the traditional solvent casting method raises concerns pertaining toxicity. Heated roll milling technology was included into the fabrication process to achieve a solvent-free biomaterial. The ideal substrate environment that promotes cellular proliferation has been a persistent area of interest in tissue engineering. Other than being biocompatible, the issue of cell proliferation is also important and is hypothesized as a function of the stiffness of the substrate material. This paper reports on experiments carried out to investigate and verify the effect of stiffness of the PCL membrane on fibroblast cell proliferation. Results indicated that 3T3 fibroblasts, belonging to soft tissues, prefer to proliferate in a lower stiffness (0.05 ± 0.01 N/mm) environment, which is closer to its native environment.