Photocrosslinkable Poly Research Articles

Photocrosslinking of sulfonated poly(arylene ether sulfone) in a swollen state

Novel photocrosslinkable sulfonated poly(arylene ether sulfone)s containing chalcone moieties in the polymer backbone (SPAEF) were synthesized from 4,4′-dihydroxychalcone (4DHC), 4,4′-difluoro-diphenylsulfone-3,3′-disulfonate (SDFDPS) and decafluorobiphenyl (DFBP). We introduced a new strategy to crosslink photosensitive polymer electrolyte membranes by UV irradiation in a swollen state in order to preserve the interconnected hydrophilic channels in the hydrated SPAEF electrolyte membrane. Photocrosslinked membranes showed desired effects of improved mechanical properties with significantly low methanol diffusion coefficient, while maintaining high proton conductivity. SPAEF membranes after the photocrosslinking exhibited a proton/methanol selectivity of 7.6 × 105 S s cm−3 at 30 °C, which is 21 times higher than that of Nafion® 117. This novel photocrosslinking strategy also improved oxidative and hydrolytic stabilities of polymer membranes which are desirable for direct methanol fuel cell application.

Encoding cell-instructive cues to PEG-based hydrogels via triple helical peptide assembly

Effective synthetic tissue engineering scaffolds mimic the structure and composition of natural extracellular matrix (ECM) to promote optimal cellular adhesion, proliferation, and differentiation. Among many proteins of the ECM, collagen and fibronectin are known to play a key role in the scaffold's structural integrity as well as its ability to support cell adhesion. Here, we present photocrosslinked poly(ethylene glycol) diacrylate (PEGDA) hydrogels displaying collagen mimetic peptides (CMPs) that can be further conjugated to bioactive molecules via CMP-CMP triple helix association. Pre-formed PEGDA-CMP hydrogels can be encoded with varying concentration of cell-signaling CMP-RGD peptides similar to cell adhesive fibronectin decorating the collagen fibrous network by non-covalent binding. Furthermore, the triple helix mediated encoding allows facile generation of spatial gradients and patterns of cell-instructive cues across the cell scaffold that simulate distribution of insoluble factors in the natural ECM.

Thermally responsive rolling of thin gel strips with discrete variations in swelling

The process by which spatial variations in growth transform two-dimensional elastic membranes into three-dimensional shapes is both a fundamentally interesting mechanism of shape selection and a powerful tool for the preparation of responsive materials. From the perspective of lithographic patterning of thin gel sheets, it is most straightforward to prepare materials consisting of discrete regions with different degrees of swelling. However, the sharp variations in swelling at the boundaries between such regions make it impossible for the sheet to adopt a configuration that is free of in-plane stresses everywhere. Thus, the deformation of such materials is not well understood. Here, we consider the geometrically simple case of a photo-crosslinkable poly(N-isopropylacrylamide) copolymer patterned into thin rectangular strips divided into one high- and one low-swelling region. When swelled in an aqueous medium at 22 °C, the sheet rolls into a three-dimensional shape consisting of two nearly cylindrical regions connected by a transitional neck. Heating to 50 °C leads to fully reversible de-swelling back to a flat configuration. We propose a scaling argument based on a balance between stretching and bending energies that relates the curvature of the 3D shape to the width and thickness of the strip, find good agreement with experimental data and numerical simulations, and further demonstrate how this simple geometry provides a powerful route for the fabrication of self-folding stimuli-responsive micro-devices.

Liquid crystalline and photocrosslinkable poly(4,4′‐stilbeneoxy) alkylarylphosphates

AbstractThree series of liquid crystalline and photocrosslinkable poly(4,4′‐stilbeneoxy) alkylarylphosphates were synthesized from various 4,4′‐bis(m‐hydroxyalkyloxy)stilbenes (m = 2, 4, 6, 8, 10) and arylphosphorodichloridates in chloroform by solution polycondensation method. Polarized optical microscope (POM) and differential scanning calorimetry (DSC) observations revealed that polymers containing less than four methylene spacer groups did not exhibit liquid crystalline (LC) texture, possibly due to smaller microdomain and restricted movement of the mesogen. In contrast, polymers containing more than four methylene spacer group established LC texture, which has been attributed to the larger monodomain and free movement of mesogens. Thermogravimetric analysis (TGA) data indicated that thermal stability and char yield decreased with increasing flexible methylene spacer groups, increased significantly for biphenyloxy and 1‐naphthyloxy containing polymers than that of phenyloxy containing polymers ascribed to increasing aromaticity, size, and number of aromatic rings. Photocrosslinking of stilbene containing polymers has been shown to proceed via 2π‐2π cycloaddition reaction by Ultra‐violet (UV) and fluorescence. The rate photocrosslinking has been found to increase with increasing number of methylene group in the main chain. The aromaticity of the side chain also increases the rate of crosslinking. POLYM. ENG. SCI., 2012. © 2011 Society of Plastics Engineers

Photocrosslinked poly(ester anhydride)s for peptide delivery: Effect of oligomer hydrophobicity on PYY3-36 delivery

The treatment for many diseases can be improved by developing more efficient peptide delivery technologies, for example, biodegradable polymers. In this work, photocrosslinked poly(ester anhydride)s based on functionalized poly(ε-caprolactone) oligomers were investigated for their abilities to achieve controlled peptide delivery. The effect of oligomer hydrophobicity on erosion and peptide release from poly(ester anhydride)s was evaluated by developing a sustained subcutaneous delivery system for an antiobesity drug candidate, peptide YY3-36 (PYY3-36). Oligomer hydrophobicity was modified with alkenylsuccinic anhydrides containing a 12-carbon alkenyl chain. PYY3-36 was mixed as a solid powder with methacrylated poly(ester anhydride) precursors, and this mixture was photocrosslinked at room temperature to form an implant for subcutaneous administration in rats. The oligomer hydrophobicity controlled the polymer erosion and PYY3-36 release as the increased hydrophobicity via the alkenyl chain prolonged polymer erosion in vitro and sustained in vivo release of PYY3-36. In addition, photocrosslinked poly(ester anhydride)s increased the bioavailability of PYY3-36 by up to 20-fold in comparison with subcutaneous administration of solution, evidence of remarkably improved delivery. In conclusion, this work demonstrates the suitability of photocrosslinked poly(ester anhydride)s for use in peptide delivery.

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.

The influence of stereolithographic scaffold architecture and composition on osteogenic signal expression with rat bone marrow stromal cells

Scaffold design parameters, especially physical construction factors such as mechanical stiffness of substrate materials, pore size of 3D porous scaffolds, and channel geometry, are known to influence the osteogenic signal expression and subsequent differentiation of a transplanted cell population. In this study of photocrosslinked poly(propylene fumarate) (PPF) and diethyl fumarate (DEF) scaffolds, the effect of DEF incorporation ratio and pore size on the osteogenic signal expression of rat bone marrow stromal cells (BMSCs) was investigated. Results demonstrated that DEF concentrations and pore sizes that led to increased scaffold mechanical stiffness also upregulated osteogenic signal expression, including bone morphogenic protein-2 (BMP-2), fibroblast growth factors-2 (FGF-2), transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor (VEGF), and Runx2 transcriptional factor. Similar scaffold fabrication parameters supported rapid BMSC osteoblastic differentiation, as demonstrated by increased alkaline phosphatase (ALP) and osteocalcin expression. When scaffolds with random architecture, fabricated by porogen leaching, were compared to those with controlled architecture, fabricated by stereolithography (SLA), results showed that SLA scaffolds with the highly permeable and porous channels also have significantly higher expression of FGF-2, TGF-β1, and VEGF. Subsequent ALP expression and osteopontin secretion were also significantly increased in SLA scaffolds. Based upon these results, we conclude that scaffold properties provided by additive manufacturing techniques such as SLA fabrication, particularly increased mechanical stiffness and high permeability, may stimulate dramatic BMSC responses that promote rapid bone tissue regeneration.

Development of Photocrosslinkable Urethane-Doped Polyester Elastomers for Soft Tissue Engineering.

Finding an ideal biomaterial with the proper mechanical properties and biocompatibility has been of intense focus in the field of soft tissue engineering. This paper reports on the synthesis and characterization of a novel crosslinked urethane-doped polyester elastomer (CUPOMC), which was synthesized by reacting a previously developed photocrosslinkable poly (octamethylene maleate citrate) (POMC) prepolymers (pre-POMC) with 1,6-hexamethylene diisocyanate (HDI) followed by thermo- or photo-crosslinking polymerization. The mechanical properties of the CUPOMCs can be tuned by controlling the molar ratios of pre-POMC monomers, and the ratio between the prepolymer and HDI. CUPOMCs can be crosslinked into a 3D network through polycondensation or free radical polymerization reactions. The tensile strength and elongation at break of CUPOMC synthesized under the known conditions range from 0.73±0.12MPa to 10.91±0.64MPa and from 72.91±9.09% to 300.41±21.99% respectively. Preliminary biocompatibility tests demonstrated that CUPOMCs support cell adhesion and proliferation. Unlike the pre-polymers of other crosslinked elastomers, CUPOMC pre-polymers possess great processability demonstrated by scaffold fabrication via a thermally induced phase separation method. The dual crosslinking methods for CUPOMC pre-polymers should enhance the versatile processability of the CUPOMC used in various conditions. Development of CUPOMC should expand the choices of available biodegradable elastomers for various biomedical applications such as soft tissue engineering.

The effect of the Hofmeister series on the deswelling isotherms of poly(N-isopropylacrylamide) and poly(N,N-diethylacrylamide)

The influence of Na2SO4, NaCl, NaBr, and NaI was studied on the deswelling isotherms of thin films of photo-crosslinked poly(N-isopropylacrylamide) and poly(N,N-diethylacrylamide) to help elucidate the mechanisms by which ions of the Hofmeister series affect the solubility of neutral, amide-based polymers. The films were characterized with both ellipsometry and FTIR to determine both water content and the frequency of the CO, N–H, and CH3 vibrations associated with the polymers. When compared at the same water content, the frequency of the N–H bend in poly(NIPAAm) red-shifts in the order I− > Cl− > Br− > SO42−. The red-shift is consistent with disrupted hydrogen bonding of the N–H moiety due to an ion–dipole attraction. The CO stretch on the other hand is insensitive to the ion, suggesting that the ion pairs primarily with the partially positive end of the HN–CO dipole. For poly(DEAAm), which lacks an N–H moiety, the CO stretch is now sensitive to the ion, with the trend following the order of the ion in the Hofmeister series. Both of these findings signify that I− > Cl− > Br− > SO42− with respect to the strength of the ion–dipole interaction. Moreover, the ion–dipole interaction is stronger in poly(NIPAAm) than poly(DEAAm), suggesting that the specificity of the Hofmeister ions arises from the effect of vicinal groups on the amide dipole.

Synthesis and manufacture of photocrosslinkable poly(caprolactone)-based three-dimensional scaffolds for tissue engineering applications

It is known that the body can efficiently repair hard tissue (bone) micro fractures by suturing the defect through the deposition of minerals resulting in an area that is stronger post-injury. Larger defects, however, generally cause more trouble since the body is incapable of repairing them. Bone defects can occur as a result of congenital abnormalities, trauma, or disease. Traditional methods for addressing these defects have involved the use of acellular cadaverous bone or autologous bone. Both contain innate prob- lems associated with them; the former method can result in disease transmission, as well as very low integration with the host due to the lack of viable cells while the latter is associated with two surgical sites and morbidity at the donor site. Alternative methods have been developed, but no method has yet provided a satisfactory solution. As a result, resear- chers and the medical community are turning toward the promising fields of biomaterial development and tissue engineering to develop new materials and me- thods of bone regeneration. In this work, a design of experiments (DOE) approach was performed to ren- der commercially available biodegradable polymers (Poly(caprolactone)-diol/triol) photocrosslinkable and resultantly manufacturable using stereolithography (SL), a rapid prototyping technology. To perform the investigations, a commercial SL system (Viper HA, 3D Systems, Valencia, CA) equipped with a solid state laser system (355 nm wavelength) was used to manu-facture synthesized poly(caprolactone) trifuma- rate (PCLtF) 3D porous constructs. Results of the work conducted produced constructs which provided pro- mising chemical and biological results for the in- tended application.

Compartmentalized Photoreactions within Compositionally Anisotropic Janus Microstructures

We demonstrate spatially controlled photoreactions within bicompartmental microparticles and microfibers. Selective photoreactions are achieved by anisotropic incorporation of photocrosslinkable poly(vinyl cinnamate) in one compartment of either colloids or microfibers. Prior to photoreaction, bicompartmental particles, and fibers were prepared by EHD co-jetting of two compositionally distinct polymer solutions. Physical and chemical anisotropy was confirmed by confocal laser scanning microscopy, Fourier-transformed infrared spectroscopy, and scanning electron microscopy. The data indicate adjustment of polymer concentrations of the jetting solutions to be the determining factors for particle and fiber structures. Subsequent exposure of poly(vinyl cinnamate)-based particles and fibers to UV light at 254 nm resulted in spatially controlled crosslinking. Treatment of the crosslinked bicompartmental colloids with chloroform produced half-moon shaped objects. These hemishells exhibited a distinct porous morphology with pore sizes in the range of 70 nm. Based on this novel synthetic approach, Janus-type particles and fibers can be prepared by EHD co-jetting and can be selectively photocrosslinked without the need for masks or selective laser writing.

Photosensitive poly(ether sulfone)s for thiol/ene UV curable coatings: synthesis, characterization and crosslinking

AbstractNovel photocrosslinkable poly(ether sulfone)s copolymers with allyl pendants (AS-PES) have been synthesized from 3,3’-diallyl-4,4’-dihydroxydiphenyl sulfone (DA-DHDPS), 4,4’-dihydroxydiphenyl sulfone (DHDPS) and 4,4’- dichlorophenylsulfone (DCDPS). The resulting polymers could be photocrosslinked in the presence of thiol at room temperature. The crosslinking process was monitored by “Real Time Fourier Transform Infrared Spectroscopy” (RTIR). It proves that a small amount (1.0 wt%) of the thiol crosslinker addition is sufficient to form a chemical network under UV irradiation. After UV curing, AS-PES-20 coating showed high Tg, good thermal stability and excellent resistance to the acid, salt, and alkali. Accordingly, this method could successfully provide a new approach to make rapidly photocrosslinking poly(ether sulfone) coatings without losing their good thermal properties.

Photo-crosslinked poly(trimethylene carbonate)-fumarate/n-vinyl pyrrolidone networks for the controlled release of proteins

Photo-crosslinked poly(trimethylene carbonate)-fumarate/n-vinyl pyrrolidone networks for the controlled release of proteins

Osmotic-driven Release of Papaverine Hydrochloride From Novel poly(decane-co-tricarballylate) Elastomeric Matrices

We have recently reported on the synthesis, characterization and biocompatibility of a novel family of visible-light photocrosslinked poly(diol-co-tricarballylate) elastomers intended for use in drug delivery and tissue engineering applications. In this work, the osmotic-driven controlled release of the water-soluble drug, papaverine hydrochloride, from poly(decane-co-tricarballylate) elastomeric cylindrical monoliths is reported. We also examined the influence of various parameters such as the degree of prepolymer acrylation, crosslinking density and the incorporation of osmotic excipients such as trehalose on the release kinetics of the drug. The release rate of papaverine hydrochloride was found to decrease in dissolution media of higher osmotic activity as an indication of the predominant involvement of the osmotic-driven release mechanism from the elastomeric devices. The drug release rate was also found to be dependent on the degree of macromer acrylation. Furthermore, it was found that coformulating papaverine hydrochloride with trehalose increases the release rate without altering the linear nature of the drug release kinetics. A new delivery vehicle composed of biodegradable poly(decane-co-tricarballylate) elastomers was demonstrated to be a promising and effective matrix for linear, constant and controllable osmotic-driven release of drugs.

Biocompatible photocrosslinked poly(ester anhydride) based on functionalized poly(ε-caprolactone) prepolymer shows surface erosion controlled drug release in vitro and in vivo

Star-shaped poly(ε-caprolactone) oligomers functionalized with succinic anhydride were used as prepolymers to prepare photocrosslinked poly(ester anhydride) to evaluate their in vivo drug delivery functionality and biocompatibility. Thus, in this work, erosion, drug release and safety of the photocrosslinked poly(ester anhydride) were examined in vitro and in vivo. A small water-soluble drug, propranolol HCl ( M w 296 g/mol, solubility 50 mg/ml), was used as the model drug in an evaluation of the erosion controlled release. Drug-free and drug-loaded (10–60% w/w) poly(ester anhydride) discoids eroded in vitro (pH 7.4 buffer, + 37 °C) linearly within 24–48 h. A strong correlation between the polymer erosion and the linear drug release in vitro was observed, indicating that the release had been controlled by the erosion of the polymer. Similarly, in vivo studies (s.c. implantation of discoids in rats) indicated that surface erosion controlled drug release from the discoids (drug loading 40% w/w). Oligomers did not decrease cell viability in vitro and the implanted discoids (s.c., rats) did not evoke any cytokine activity in vivo. In summary, surface erosion controlled drug release and the safety of photocrosslinked poly(ester anhydride) were demonstrated in this study.

Development of d-allose sensor on the basis of three strategic enzyme reactions

Rare sugars are defined as monosaccharides and their derivatives that rarely exist in nature, according to the International Society of Rare Sugars. d-Allose (3-epi d-glucose) is one of the rare sugars, for which various physiological activities have recently been found, with increasing attention to its applications to bio-industry. Until now, however, there is no convenient method of measuring these sugars in a specific manner. For detecting d-allose, three consecutive enzyme reactions were devised by fabricating of a reaction batch chamber packed with l-rhamnose isomerase (LRI), d-tagatose 3-epimerase (DTE) and a screen-printed electrode, on which d-fructose dehydrogenase (DFDH) was immobilized. To obtain a substantial sensing system, extensive experimental parameters were optimized. These included the concentration of photo-crosslinkable poly (vinyl alcohol) bearing stilbazolium groups (PVA-SbQ), reaction ratios, and temperature of the batch chamber. By adopting the three consecutive enzyme reactions, an undesirable reverse reaction was minimized. As a result, the developed sensor system exhibited a good linear response on d-allose in the range from 0.1 to 50 mM ( r 2 = 0.998). The system has an apparent advantage over the previous chromatography approach in terms of simplicity and inexpensiveness.

Long-term stable dye-sensitized solar cells based on UV photo-crosslinkable poly(ethylene glycol) and poly(ethylene glycol) diacrylate based electrolytes

UV photo-crosslinkable polymer electrolytes based on poly(ethylene glycol) (PEG) and poly(ethylene glycol) diacrylate (PEGDA) were used in dye-sensitized solar cells (DSSCs). PEG and bifunctional PEGDA formed a crosslinked structure upon UV light illumination, confirmed by the solubility test and FTIR spectroscopy. The polymeric electrolyte was prepared by photo-polymerization after injecting the monomer electrolyte solution into the porous film in order to make close contact with the TiO 2 porous film. Under AM 1.5 (100 mW/cm 2) light irradiation for up to 20 min, a maximum 62% increase in the photo-conversion efficiency ( η%) was observed. The DSSCs with the crosslinkable PEG/PEGDA based polymer electrolyte showed improved long-term stability in comparison to those with electrolytes containing only PEG. Also, the effects of solvent on stability of the DSSCs were investigated.

Controlled fabrication of polymer microgels by polymer-analogous gelation in droplet microfluidics

We fabricate thermo-responsive polymer microgels by combining microfluidic pre-gel emulsification with polymer-analogous gelation. This separates the microgel formation from the polymer synthesis; it combines highly controlled microfluidic templating with the great flexibility of preparative polymer chemistry, allowing each to be controlled independently. We produce monodisperse pre-gel droplets from semidilute solutions of photocrosslinkable poly(N-isopropylacrylamide) precursors. The size and morphology of these droplets can be precisely controlled by the microfluidic emulsification, provided the molecular weight of the precursor is limited. Using polymer-analogous gelation rather than monomer chain-growth gelation yields gels with a higher efficiency of crosslinking and a greater homogeneity on nano- and micrometre scales, as determined by oscillatory shear rheology, static light scattering, and optical microscopy. We also demonstrate the applicability of our method to fabricate microgel particles with well-defined concentrations of functional sites.

Poly(ɛ-caprolactone) acrylates synthesized using a facile method for fabricating networks to achieve controllable physicochemical properties and tunable cell responses

We present a facile method to synthesize photo-crosslinkable poly(ε-caprolactone) acrylates (PCLAs) and reveal tunable cell responses to photo-crosslinked PCLAs. Including three PCL diacrylates (PCLDAs) and two triacrylates (PCLTAs), PCLAs could be fabricated into polymer networks with controllable physical properties to satisfy diverse tissue-engineering needs, for example, bone and nerve regeneration. This novel synthetic method used potassium carbonate (K2CO3) as the proton scavenger other than widely used triethylamine (TEA) in order to avoid colorization and potential toxicity from the side reaction between TEA and acryloyl chloride. In addition, this new method significantly simplified the purification step of the polymer products because of the convenient separation between inorganic particles and organic polymer solution. Through combining crystallite-based physical network and crosslink-based chemical network together, we could modulate material properties and consequently control cell responses. Thermal properties such as glass transition temperature (Tg), melting temperature (Tm), and crystallinity (χc) of both uncrosslinked and crosslinked PCLAs were correlated with their mechanical and rheological properties. Surface characteristics such as surface morphology, hydrophilicity, and its capability of adsorbing serum proteins from cell culture medium were also examined for crosslinked PCLA disks. Mouse MC3T3 cells and rat Schwann precursor cell line (SPL201) cells were applied to evaluate the in vitro biocompatibility of these polymeric networks and the roles of surface chemistry, crystallinity, and stiffness in regulating cell attachment, spreading and proliferation collectively. Semi-crystalline PCLA network with the highest χc and Tm was found to support cell attachment, spreading, and proliferation best among all these five systems.

Porous Biodegradable Scaffold: Predetermined Porosity by Dissolution of Poly(ester‐anhydride) Fibers from Polyester Matrix

A novel selective leaching method for the porogenization of the biodegradable scaffolds was developed. Continuous, predetermined pore structure was prepared by dissolving fast eroding poly(epsilon-caprolactone)-based poly(ester-anhydride) fibers from the photo-crosslinked poly(epsilon-caprolactone) matrix. The porogen fibers dissolved in the phosphate buffer (pH 7.4, 37 degrees C) within a week, resulting in the porosity that replicated exactly the single fiber dimensions and the overall arrangement of the fibers. The amount of the porosity, estimated with micro-CT, corresponded with the initial amount of the fibers. The potential to include bioactive agents in the porogen fibers was demonstrated with the bioactive glass.