Bovine Serum Albumin Effect on Collapsing PNIPAM Chains in Aqueous Solutions: Spin Label and Spin Probe Study.

The influence of bovine serum albumin (BSA) on collapsing poly(N-isopropylacrylamide) (PNIPAM) chains was studied with turbidimetry and spin probe and spin label electron paramagnetic resonance spectroscopy. An increased ratio of collapsed chains in aqueous solutions in the narrow temperature region near the LCST appeared in the presence of 2.5-10 wt% BSA. The spin probe EPR data indicate that the inner cavities of the BSA dimers are probably responsive to the capture of small hydrophobic or amphiphilic molecules, such as TEMPO nitroxyl radical. The observed features of the structure and dynamics of inhomogeneities of aqueous PNIPAM-BSA solutions, including their mutual influence on the behavior of the polymer and protein below the LCST, should be considered when developing and investigating PNIPAM-based drug delivery systems.

Resveratrol's Impact on the Chondrogenic Reagents' Effects in Cell Sheet Cultures of Wharton's Jelly-Derived MSCs.

Human Wharton's jelly mesenchymal stem cells (hWJ-MSCs) are of great interest in tissue engineering. We obtained hWJ-MSCs from four patients, and then we stimulated their chondrogenic phenotype formation in vitro by adding resveratrol (during cell expansion) and a canonical Wnt pathway activator, LiCl, as well as a Rho-associated protein kinase inhibitor, Y27632 (during differentiation). The effects of the added reagents on the formation of hWJ-MSC sheets destined to repair osteochondral injuries were investigated. Three-dimensional hWJ-MSC sheets grown on P(NIPAM-co-NtBA)-based matrices were characterized in vitro and in vivo. The combination of resveratrol and LiCl showed effects on hWJ-MSC sheets similar to those of the basal chondrogenic medium. Adding Y27632 decreased both the proportion of hypertrophied cells and the expression of the hyaline cartilage markers. In vitro, DMSO was observed to impede the effects of the chondrogenic factors. The mouse knee defect model experiment revealed that hWJ-MSC sheets grown with the addition of resveratrol and Y27632 were well integrated with the surrounding tissues; however, after 3 months, the restored tissue was identical to that of the naturally healed cartilage injury. Thus, the combination of chondrogenic supplements may not always have additive effects on the progress of cell culture and could be neutralized by the microenvironment after transplantation.

Visible-Light-Induced Cationic Polymerization of Isobutylene: A Route toward the Synthesis of End-Functional Polyisobutylene.

The visible-light-induced cationic polymerization of isobutylene with a dimanganese decacarbonyl (Mn2(CO)10)/diphenyl iodonium hexafluorophosphate (Ph2I+PF6-) photoinitiating system in a CH2Cl2/n-hexane mixture at -30 °C was reported. It was shown that polymerization is initiated by chloromethylisobutyl carbocations generated by the oxidation of chloromethylisobutyl radicals by Ph2I+PF6-. The latter are formed via chlorine abstraction from solvent (CH2Cl2) by MnCO5· radicals, which are generated by the photoinduced decomposition of Mn2(CO)10, followed by single isobutylene addition. This initiating system allowed us to synthesize valuable low molecular weight polyisobutylene with a relatively low polydispersity (Mn = 2000-3000 g mol-1; D < 1.7) and high content of exo-olefin end groups (up to 90%). The molecular weight of polyisobutylenes could be easily controlled in the range from 2000 to 12000 g mol-1 by changing the diphenyl iodonium salt concentration. Poly(ß-pinene) with Mn = 5000 g mol-1 and D ∼ 2.0 was successfully synthesized using the same photoinitiating system.

Phosphazene Functionalized Silsesquioxane-Based Porous Polymer as Thermally Stable and Reusable Catalyst for Bulk Ring-Opening Polymerization of ε-Caprolactone.

The bulk ring-opening polymerization (ROP) of ε-caprolactone using phosphazene-containing porous polymeric material (HPCP) has been studied at high reaction temperatures (130-150 °C). HPCP in conjunction with benzyl alcohol as an initiator induced the living ROP of ε-caprolactone, affording polyesters with a controlled molecular weight up to 6000 g mol-1 and moderate polydispersity (Ð~1.5) under optimized conditions ([BnOH]/[CL] = 50; HPCP: 0.63 mM; 150 °C). Poly(ε-caprolactone)s with higher molecular weight (up to Mn = 14,000 g mol-1, Ð~1.9) were obtained at a lower temperature, at 130 °C. Due to its high thermal and chemical stability, HPCP can be reused for at least three consecutive cycles without a significant decrease in the catalyst efficiency. The tentative mechanism of the HPCP-catalyzed ROP of ε-caprolactone, the key stage of which consists of the activation of the initiator through the basic sites of the catalyst, was proposed.

Aluminum Salen Complexes Modified with Unsaturated Alcohol: Synthesis, Characterization, and Their Activity towards Ring-Opening Polymerization of ε-Caprolactone and D,L-Lactide.

A highly efficient one-step approach to the macromonomer synthesis using modified aluminum complexes as catalysts of ring-opening polymerization (ROP) of ε-caprolactone and D,L-lactide was developed. The syntheses, structures, and catalytic activities of a wide range of aluminum salen complexes, 3a-c, functionalized with unsaturated alcohol (HO(CH2)4OCH=CH2) are reported. X-Ray diffraction studies revealed a tetragonal pyramidal structure for 3c. Among the complexes 3a-c, the highest activity in bulk ROP of ε-caprolactone and D,L-lactide was displayed by 3b, affording polyesters with controlled molecular weights at low monomer to initiator ratios (Mn up to 15,000 g mol-1), relatively high polydispersities (Ð~1.8) and high number-average functionalities (Fn up to 85%).

Structure and Dynamics of Inhomogeneities in Aqueous Solutions of Graft Copolymers of N-Isopropylacrylamide with Lactide (P(NIPAM-graft-PLA)) by Spin Probe EPR Spectroscopy.

Coil-to-globule transition and dynamics of inhomogeneities in aqueous solutions of graft copolymers of NIPAM with different content of oligolactide groups were studied using spin probe continuous wave EPR spectroscopy. The technique of the suppressing of TEMPO as spin probe by spin exchange with Cu2+ ions was applied. This approach allowed us to detect individual EPR spectra of the probe in collapsed globules and estimate its magnetic and dynamic parameters reliably. The formation of inhomogeneities at temperatures lower than the volume phase transition temperature measured via transmission, and differential scanning calorimetry was fixed. An increase in oligolactide content in copolymers leads to the formation of looser globules, allowing for the exchange of the probe molecules between the globules and the external solution.

Macromolecular crowding transforms regenerative medicine by enabling the accelerated development of functional and truly three-dimensional cell assembled micro tissues.

Scaffold-free in vitro organogenesis exploits the innate ability of cells to synthesise and deposit their own extracellular matrix to fabricate tissue-like assemblies. Unfortunately, cell-assembled tissue engineered concepts require prolonged ex vivo culture periods of very high cell numbers for the development of a borderline three-dimensional implantable device, which are associated with phenotypic drift and high manufacturing costs, thus, hindering their clinical translation and commercialisation. Herein, we report the accelerated (10 days) development of a truly three-dimensional (338.1 ± 42.9 µm) scaffold-free tissue equivalent that promotes fast wound healing and induces formation of neotissue composed of mature collagen fibres, using human adipose derived stem cells seeded at only 50,000 cells/cm2 on an poly (N-isopropylacrylamide-co-N-tert-butylacrylamide (PNIPAM86-NTBA14) temperature-responsive electrospun scaffold and grown under macromolecular crowding conditions (50 µg/ml carrageenan). Our data pave the path for a new era in scaffold-free regenerative medicine.

Biomaterials Based on Carbon Nanotube Nanocomposites of Poly(styrene-b-isobutylene-b-styrene): The Effect of Nanotube Content on the Mechanical Properties, Biocompatibility and Hemocompatibility.

Nanocomposites based on poly(styrene-block-isobutylene-block-styrene) (SIBS) and single-walled carbon nanotubes (CNTs) were prepared and characterized in terms of tensile strength as well as bio- and hemocompatibility. It was shown that modification of CNTs using dodecylamine (DDA), featured by a long non-polar alkane chain, provided much better dispersion of nanotubes in SIBS as compared to unmodified CNTs. As a result of such modification, the tensile strength of the nanocomposite based on SIBS with low molecular weight (Mn = 40,000 g mol-1) containing 4% of functionalized CNTs was increased up to 5.51 ± 0.50 MPa in comparison with composites with unmodified CNTs (3.81 ± 0.11 MPa). However, the addition of CNTs had no significant effect on SIBS with high molecular weight (Mn~70,000 g mol-1) with ultimate tensile stress of pure polymer of 11.62 MPa and 14.45 MPa in case of its modification with 1 wt% of CNT-DDA. Enhanced biocompatibility of nanocomposites as compared to neat SIBS has been demonstrated in experiment with EA.hy 926 cells. However, the platelet aggregation observed at high CNT concentrations can cause thrombosis. Therefore, SIBS with higher molecular weight (Mn~70,000 g mol-1) reinforced by 1-2 wt% of CNTs is the most promising material for the development of cardiovascular implants such as heart valve prostheses.

Inhomogeneities in PNIPAM Aqueous Solutions: The Inside View by Spin Probe EPR Spectroscopy.

Coil to globule transition in poly(N-isopropylacrylamide) aqueous solutions was studied using spin probe continuous-wave electronic paramagnetic resonance (CW EPR) spectroscopy with an amphiphilic TEMPO radical as a guest molecule. Using Cu(II) ions as the "quencher" for fast-moving radicals in the liquid phase allowed obtaining the individual spectra of TEMPO radicals in polymer globule and observing inhomogeneities in solutions before globule collapsing. EPR spectra simulations confirm the formation of molten globules at the first step with further collapsing and water molecules coming out of the globule, making it denser.

A Hydrophobic Derivative of Ciprofloxacin as a New Photoinitiator of Two-Photon Polymerization: Synthesis and Usage for the Formation of Biocompatible Polylactide-Based 3D Scaffolds.

A hydrophobic derivative of ciprofloxacin, hexanoylated ciprofloxacin (CPF-hex), has been used as a photoinitiator (PI) for two-photon polymerization (2PP) for the first time. We present, here, the synthesis of CPF-hex and its application for 2PP of methacrylate-terminated star-shaped poly (D,L-lactide), as well a systematic study on the optical, physicochemical and mechanical properties of the photocurable resin and prepared three-dimensional scaffolds. CPF-hex exhibited good solubility in the photocurable resin, high absorption at the two-photon wavelength and a low fluorescence quantum yield = 0.079. Structuring tests showed a relatively broad processing window and revealed the efficiency of CPF-hex as a 2PP PI. The prepared three-dimensional scaffolds showed good thermal stability; thermal decomposition was observed only at 314 °C. In addition, they demonstrated an increase in Young's modulus after the UV post-curing (from 336 ± 79 MPa to 564 ± 183 MPa, which is close to those of a cancellous (trabecular) bone). Moreover, using CPF-hex as a 2PP PI did not compromise the scaffolds' low cytotoxicity, thus they are suitable for potential application in bone tissue regeneration.

Design of cross-linked polyisobutylene matrix for efficient encapsulation of quantum dots.

Photoluminescent quantum dots (QDs) are a prominent example of nanomaterials used in practical applications, especially in light-emitting and light-converting devices. Most of the current applications of QDs require formation of thin films or their incorporation in solid matrices. The choice of an appropriate host material capable of preventing QDs from degradation and developing a process of uniform incorporation of QDs in the matrix have become essential scientific and technological challenges. In this work, we developed a method of uniform incorporation of Cu-Zn-In-S (CZIS) QDs into a highly protective cross-linked polyisobutylene (PIB) matrix with high chemical resistance and low gas permeability. Our approach involves the synthesis of a methacrylate-terminated three-arm star-shaped PIB oligomeric precursor capable of quick formation of a robust 3D polymer network upon exposure to UV-light, as well as the design of a special ligand introducing short PIB chains onto the surface of the QDs, thus providing compatibility with the matrix. The obtained cross-linked QDs-in-polymer composites underwent a complex photostability test in air and under vacuum as well as a chemical stability test. These tests found that CZIS QDs in a cross-linked PIB matrix demonstrated excellent photo- and chemical stability when compared to identical QDs in widely used polyacrylate-based matrices. These results make the composites developed excellent materials for the fabrication of robust, stable and durable transparent light conversion layers.

Biocompatible Nanocomposites Based on Poly(styrene-block-isobutylene-block-styrene) and Carbon Nanotubes for Biomedical Application.

In this study, we incorporated carbon nanotubes (CNTs) into poly(styrene-block-isobutylene-block-styrene) (SIBS) to investigate the physical characteristics of the resulting nanocomposite and its cytotoxicity to endothelial cells. CNTs were dispersed in chloroform using sonication following the addition of a SIBS solution at different ratios. The resultant nanocomposite films were analyzed by X-ray microtomography, optical and scanning electron microscopy; tensile strength was examined by uniaxial tension testing; hydrophobicity was evaluated using a sessile drop technique; for cytotoxicity analysis, human umbilical vein endothelial cells were cultured on SIBS-CNTs for 3 days. We observed an uneven distribution of CNTs in the polymer matrix with sporadic bundles of interwoven nanotubes. Increasing the CNT content from 0 wt% to 8 wt% led to an increase in the tensile strength of SIBS films from 4.69 to 16.48 MPa. The engineering normal strain significantly decreased in 1 wt% SIBS-CNT films in comparison with the unmodified samples, whereas a further increase in the CNT content did not significantly affect this parameter. The incorporation of CNT into the SIBS matrix resulted in increased hydrophilicity, whereas no cytotoxicity towards endothelial cells was noted. We suggest that SIBS-CNT may become a promising material for the manufacture of implantable devices, such as cardiovascular patches or cusps of the polymer heart valve.

A Catalyst Platform for Unique Cationic (Co)Polymerization in Aqueous Emulsion.

Sodium dodecyl benzene sulfonate (DBSNa) surfactants, with a polydisperse and hyperbranched structure, combined with different rare earth metal salts generate highly water-dispersible Lewis acid surfactant combined catalysts (LASCs). This platform of new complexes promotes fast, efficient cationic polymerization of industrially relevant monomers in direct emulsion at moderate temperature. The process described here does not require high shearing, long polymerization time, or large catalyst content. It allows the reproducible generation of high-molar-mass homopolymers of pMOS, styrene, and isoprene, as well as random or multiblock copolymers of the latter two, in a simple and straightforward one-pot reaction.

Cationic polymerization of vinyl monomers in aqueous media: from monofunctional oligomers to long-lived polymer chains.

Polymer latexes are easily prepared on a multimillion ton scale in industry using free radical initiated emulsion and suspension polymerizations in water, a cheap, nonviscous, heat-controlling, and environmentally benign solvent. Until recently, researchers had done little investigation into ionic polymerization because even a small amount of water would easily deactivate the conventional catalysts used in these processes. In the last decade, however, cationic polymerization in aqueous media has emerged as a new and attractive method for controlling the polymerization reactions using mild experimental conditions. This Account reviews the current science of and future outlook for cationic polymerization of vinyl monomers in aqueous media. We particularly emphasize the design and evolution of catalytic systems and the precision synthesis of functional polymers. Early work to tailor the suspension and emulsion cationic polymerizations of reactive monomers such as p-methoxystyrene and vinyl ethers used long-chain strong acids, called INISURF for their dual roles as initiators and surfactants, and lanthanide triflates. These polymerization processes shared two main features: (i) all reactions (initiation, propagation, and termination) occurred at the particle interface; (ii) synthesized polymers have limits on their molecular weight, attributed to the "critical DP" effect, related to the entry of oligomers inside the particles as they become increasingly hydrophobic. The next generation of catalysts, named "Lewis acid-surfactant combined catalysts" (LASC), shifted the polymerization locus from the interface to the inside of the monomer droplets, allowing for the production of long polymer chains. Recently, catalytic systems based on boranes, (BF(3)OEt(2), B(C(6)F(5))(3), (C(6)F(4)-1,2-[B(C(6)F(5))(2)]), and (C(6)F(4)-1,2-[B(C(12)F(8))](2))), have shown great potential in controlling the cationic polymerization in "wet" solution, containing an excess of water relative to Lewis acid, or aqueous media of such industrially important monomers as styrene, cyclopentadiene, and even isobutylene.

Oligomerization of electron-deficient vinyl monomers through an ate-complex mechanism: a new role for b(c(6) f(5) )(3) lewis Acid.

The Lewis acid B(C(6) F(5) )(3) in combination with hydrosilanes exhibits remarkable activity in the oligomerization of sulfone- and phosphonate-based monomers. This process opens new routes to high-tech silicone-based materials, i.e., thermoplastic elastomers and heat-resistant polysiloxanes.