Control of Hyperbranched Structure of Polycaprolactone/Poly(ethylene glycol) Polyurethane Block Copolymers by Glycerol and Their Hydrogels for Potential Cell Delivery

A series of biodegradable amphiphilic polyurethane block copolymers with hyperbranched structure were synthesized by copolymerizing poly­(ε-caprolactone) (PCL) and poly­(ethylene glycol) (PEG) together with glycerol. The copolymers were characterized, and their composition and branch length were varied with the feeding ratio between PCL, PEG, and glycerol used. Hydrogels were formed from these copolymers by swelling of water at low polymer concentrations. The hydrogels were thixotropic, and their dynamic viscoelastic properties were dependent on the copolymer composition, branch length, and polymer concentration. Hydrolytic degradation of the hydrogels was evaluated by mass loss and changes in molecular structures. The porous morphology of the hydrogels provided good permeability for gas and nutrition. Together with the tunable rheological properties, the hydrogels were found to be suitable for 3D living cell encapsulation and delivery. The morphology of the solid copolymers was semicrystalline, while the hydrogels were totally amorphous without crystallinity, providing a mild aqueous environment for living cells. When the encapsulated cells were recovered from the hydrogels followed by subculture, they showed good cell viability and proliferation ability. The results indicate that the hyperbranched copolymers hydrogels developed in this work may be promising candidates for potential injectable cell delivery application

Exploring the spatial dimensions of nanotechnology development in China: the effects of funding and spillovers

<p>This paper investigates the factors driving nanotechnology development in Chinese regions. Advanced regions of China have spearheaded the country’s rapid growth in nanotechnology, aided by substantial support from the government. While this head start could potentially perpetuate regional inequalities through agglomeration economies, the results suggest that knowledge spillovers exert a substantially greater impact in peripheral regions compared with the advanced ones, and may thus be compensating for the limited institutional support they receive and their weak technological capabilities. This research contributes to the regional innovation literature by highlighting that a formal scientific network can counteract the forces of agglomeration economies and spur innovation in peripheral regions.</p

Exploring the spatial dimensions of nanotechnology development in China: the effects of funding and spillovers

<p>This paper investigates the factors driving nanotechnology development in Chinese regions. Advanced regions of China have spearheaded the country’s rapid growth in nanotechnology, aided by substantial support from the government. While this head start could potentially perpetuate regional inequalities through agglomeration economies, the results suggest that knowledge spillovers exert a substantially greater impact in peripheral regions compared with the advanced ones, and may thus be compensating for the limited institutional support they receive and their weak technological capabilities. This research contributes to the regional innovation literature by highlighting that a formal scientific network can counteract the forces of agglomeration economies and spur innovation in peripheral regions.</p

FRONT MATTER

Legacy description not available</p

Oxygenic Enrichment in Hybrid Ruthenium Sulfide Nanoclusters for an Optimized Photothermal Effect

Transition-metal dichalcogenide (TMD)-based nanomaterials have been extensively explored for the photonic therapy. To the best of our knowledge, near-infrared (NIR) light is a requirement for the photothermal therapy (PTT) to achieve the feature of deep-tissue penetration, whereas no obvious absorption peaks existing in the NIR region for existing TMD nanomaterials limit their therapeutic efficacy. As one category of TMD nanomaterials, ruthenium sulfide-based nanomaterials have been less exploited in biomedical applications including tumor therapy so far. Here, we develop a facile biomineralization-assisted bottom-up strategy to synthesize oxygenic hybrid ruthenium sulfide nanoclusters (RuSx NCs) by regulating the oxygen amounts and sulfur defects for the optimized PTT. By regulating the increasing initial molar ratios of Ru to S, RuSx NCs with small sizes were endowed with increasing oxygen contents and sulfur defects, leading to the photothermal conversion efficiency (PCE) increasing from 32.8 to 41.9%, which were higher than that of most small-sized inorganic photothermal nanoagents. In contrast to commercial indocyanine green, these RuSx NCs exhibited higher photostability under NIR laser irradiation. The high PCE and superior photostability allowed RuSx NCs to effectively and completely ablate cancer cells. Thus, the proposed defect engineering strategy endows RuSx NCs with an excellent photothermal effect for the PTT of tumors of living mice, which also proves the potential of further exploring the properties of RuSx NCs for future biomedical applications

FRONT MATTER

Legacy description not available</p

Supramolecular Anchoring of DNA Polyplexes in Cyclodextrin-Based Polypseudorotaxane Hydrogels for Sustained Gene Delivery

A cyclodextrin-based supramolecular hydrogel system with supramolecularly anchored active cationic copolymer/plasmid DNA (pDNA) polyplexes was studied as a sustained gene delivery carrier. A few biodegradable triblock copolymers of methoxy-poly­(ethylene glycol)-<i>b</i>-poly­(ε-caprolactone)-<i>b</i>-poly­[2-(dimethylamino)­ethyl methacrylate] (MPEG-PCL-PDMAEMA) with well-defined cationic block lengths were prepared to condense pDNA. The MPEG-PCL-PDMAEMA copolymers exhibit good ability to condense pDNA into 275–405 nm polyplexes with hydrophilic MPEG in the outer corona. The MPEG corona imparted greater stability to the pDNA polyplexes and also served as an anchoring segment when the pDNA polyplexes were encapsulated in α-CD-based supramolecular polypseudorotaxane hydrogels. More interestingly, the resultant hydrogels were able to sustain release of pDNA up to 6 days. The pDNA was released in the form of polyplex nanoparticles as it was bound electrostatically to the cationic segment of the MPEG-PCL-PDMAEMA copolymers. The bioactivity of the released pDNA polyplexes at various durations was further investigated. Protein expression level of pDNA polyplexes released over the durations was comparable to that of freshly prepared PEI polyplexes. Being thixotropic and easily prepared without using organic solvent, this supramolecular <i>in situ</i> gelling system has immense potential as an injectable carrier for sustained gene delivery

Control of PLA Stereoisomers-Based Polyurethane Elastomers as Highly Efficient Shape Memory Materials

Poly­(lactic acid) (PLA) has received increasing attention in the development of shape memory polymers (SMPs) due to its excellent physical properties and good biocompatibility. However, the intrinsically increased crystallinity of PLA at higher deformation ratios still remains a significant challenge, which remarkably restricts the chain mobility and reduces shape recovery efficiency. Being different from other types of biodegradable polymers, the diverse isomeric forms of PLA have provided great opportunities for modulation of PLA toward a favorable property by incorporating different PLA stereoisomers in one macromolecular architecture. In this paper, we report a completely amorphous PLA poly­(ester urethane) elastomer that exhibits excellent shape fixity (>99%) and shape recovery (>99%) in a time frame of seconds. By means of adjusting the stereoisomeric ratios and control over architecture, the resultant poly­(PLLA/PDLLA urethane)­s (PLDU) elastomers show a single glass transition temperature (<i>T</i>_g), as the only thermal event, in the range of 38–46 °C in a predictable manner. The elastic moduli of PLDU elastomers display a 100-fold loss during the sharp transition from a glassy to a rubbery state with temperature alternation across their corresponding <i>T</i>_g, indicating a successful manipulation of the thermo-mechanical properties by temperature as required in thermally induced SMPs. In addition, all samples display a typical elastomeric behavior with elongation at break (ε_b) greater than 400%. The effect of the stereoisomer content on the tensile modulus and elastic mechanical behavior were also systematically investigated. Together with the prominent degradation property, the new PLDU elastomers developed in this study show great potential for biomedical applications as shape memory implants

Poly(ethylene glycol) Conjugated Poly(lactide)-Based Polyelectrolytes: Synthesis and Formation of Stable Self-Assemblies Induced by Stereocomplexation

A series of pH-responsive amphiphilic poly­(<i>N</i>,<i>N</i>-dimethylaminoethyl methacrylate)-<i>block</i>-poly­(d-lactic acid)-<i>block</i>-poly­(<i>N</i>,<i>N</i>-dimethylaminoethyl methacrylate) conjugated with poly­(ethylene glycol) (D-PDLA-D@PEG) and D-PLLA-D@PEG copolymers were synthesized using a combination of ring-opening polymerization and atom-transfer radical polymerization followed by sequential quaternization of PDMAEMA chains and azide–alkyne click reaction with alkyne-end PEG. Gel permeation chromatography, nuclear magnetic resonance, and Fourier transform infrared spectroscopy results demonstrate the successful synthesis of the copolymers, and the conjugated PEG percentages in the copolymers can be tuned by the feeding ratios in the quaternization reaction. Conjugating PEG onto the PDMAEMA segments also successfully facilitated the D-PDLA-D@PEG, D-PLLA-D@PEG, and its corresponding 1:1 D/L mixtures to be dissolved directly in aqueous solution at the desired concentration range without using any organic solvents unlike the copolymers without PEG conjugation (D-PDLA-D and D-PLLA-D). We demonstrate control over micellar size, charge, and stability via three different preparation pathways, i.e., solution pH, percentages of PEG conjugation in the copolymers, and formation of PLA stereocomplex in micellar core. Static and dynamic light scattering studies demonstrate that the size of the core–shell micelles increases when the solution pH is reduced due to the protonation of the PDMAEMA segments that caused the osmotic pressure within the micelle to increase until the micelles reached a maximum size. It is interesting to note that the micelles formed by 1:1 D/L mixtures have larger swelling ratios as well as aggregation number and hydrodynamic radius that do not change significantly with pH and dilution, respectively, as compared to micelles formed from individual D or L forms of the copolymers. The enhanced stability of the pH-responsive micelles prepared by direct dissolution of the 1:1 D/L mixtures of the PEG conjugated PLA-based polyelectrolytes in aqueous medium is attributed to the stereocomplex formation between PLLA and PDLA in the micellar core as confirmed by wide-angle X-ray scattering measurements

Facile Layer-by-Layer Self-Assembly toward Enantiomeric Poly(lactide) Stereocomplex Coated Magnetite Nanocarrier for Highly Tunable Drug Deliveries

A highly tunable nanoparticle (NP) system with multifunctionalities was developed as drug nanocarrier via a facile layer-by-layer (LbL) stereocomplex (SC) self-assembly of enantiomeric poly­(l-lactic acid) (PLLA) and poly­(d-lactic acid) (PDLA) in solution using silica-coated magnetite (Fe₃O₄@SiO₂) as template. The poly­(lactide) (PLA) SC coated NPs (Fe₃O₄@SiO₂@-SC) were further endowed with different stimuli-responsiveness by controlling the outermost layer coatings with respective pH-sensitive poly­(lactic acid)-poly­(2-dimethylaminoethyl methacrylate) (PLA-D) and temperature-sensitive poly­(lactic acid)-poly­(<i>N</i>-isopropylacrylamide) (PLA-N) diblock copolymers to yield Fe₃O₄@SiO₂@SC-D and Fe₃O₄@SiO₂@SC-N NPs, respectively, while the superparamagnetic properties of Fe₃O₄ were maintained. TEM images show a clearly resolved core–shell structure with a silica layer and sequential PLA SC co/polymer coating layers in the respective NPs. The well-designed NPs possess a size distribution in a range of 220–270 nm and high magnetization of 70.8−72.1 emu/g [Fe₃O₄]. More importantly, a drug release study from the as-constructed stimuli-responsive NPs exhibited sustained release profiles and the rates of release can be tuned by variation of external environments. Further cytotoxicity and cell culture studies revealed that PLA SC coated NPs possessed good cell biocompatibility and the doxorubicin (DOX)-loaded NPs showed enhanced drug delivery efficiency toward MCF-7 cancer cells. Together with the strong magnetic sensitivity, the developed hybrid NPs demonstrate a great potential of control over the drug release at a targeted site. The developed coating method can be further optimized to finely tune the nanocarrier size and operating range of pHs and temperatures for in vivo applications