A self-healing thermogelling polymer with tunable transparency based on biomolecule alginate grafting phenylboronic acid.

Thermogelling polymers with transparency, structure stability and biocompatibility are promising for biomedicine application. In this study, a thermogelling polymer P-C5PEG with tunable transparency was developed by the reaction between alternating copolymer C5PEG and chemically modified biomolecule Alg-PBA via boronic ester bonds. The sol-to-gel transition of P-C5PEG aqueous solution sensitively responded to changes in temperature, and the critical value could be adjusted between 15 and 40 °C by varying the content of C5PEG and Alg-PBA. As the weight ratio of Alg-PBA to C5PEG was over 0.3, the transparency of as-synthesized hydrogel kept above 75 % at 37 °C. Meanwhile, immersion P-C5PEG hydrogel in CaCl2 solution significantly increased its mechanical strength by 3 times due to chelation effect. The shear-resistance and self-healing properties were ensured by dynamic boronic ester bonds due to the protective effect of hydrophobic gel network. As a drug delivery, P-C5PEG hydrogel had a swelling rate of 3748.7 ± 103 % in PBS and could continuously release fluorescein sodium within 24 h. Moreover, the in vitro degradability and cytotoxicity of P-C5PEG was confirmed. Finally, the mechanisms behind the thermogelling property and tunable transparency were revealed. Overall, this thermogelling P-C5PEG polymer, with tunable transparency and thermo-responsiveness, exhibits great potential for biomedicine application.

Compressible Hydrogels with Stabilized Chirality from Thermoresponsive Helical Dendronized Poly(phenylacetylene)s.

Fabrication of chiral hydrogels from thermoresponsive helical dendronized phenylacetylene copolymers (PPAs) carrying three-fold dendritic oligoethylene glycols (OEGs) is reported. Three different temperatures, i.e. below or above cloud point temperatures (Tcps) of the copolymers, and under freezing condition, were utilized, affording thermoresponsive hydrogels with different morphologies and mechanical properties. At room temperature, transparent hydrogels were obtained through crosslinking among different copolymer chains. Differently, opaque hydrogels with much improved mechanical properties were formed at elevated temperatures through crosslinking from the thermally dehydrated and collapsed copolymer aggregates, leading to heterogeneity for the hydrogels with highly porous morphology. While crosslinking at freezing temperature synergistically through ice templating, these amphiphilic dendronized copolymers formed hydrogels with highly porous lamellar structures, which exhibited remarkable compressible properties as human articular cartilage with excellent fatigue resistance. Amphiphilicity of the dendronized copolymers played a pivotal role in modulating the network formation during the gelation, as well as morphology and mechanical performance of the resulting hydrogels. Through crosslinking, these dendronized copolymers featured with typical dynamic helical conformations were transformed into hydrogels with unprecedently stabilized helicities due to the restrained chain mobilities in the three-dimensional networks.

An injectable thermoresponsive-hydrogel for lamellar keratoplasty: In-situ releases celastrol and hampers corneal scars.

Corneal stromal fibrosis is a common cause of visual impairment resulting from corneal injury, inflammation and surgery. Therefore, there is an unmet need for inhibiting corneal stromal fibrosis. However, bioavailability of topical eye drops is very low due to the tear and corneal barriers. In situ delivery offers a unique alternative to improve efficacy and minimize systemic toxicity. Herein, a drug delivery platform based on thermoresponsive injectable hydrogel/nano-micelles composite with in situ drug-controlled release and long-acting features is developed to prevent corneal scarring and reduce corneal stromal fibrosis in lamellar keratoplasty. The in-situ gelation hydrogels enabled direct delivery of celastrol to the corneal stroma. In vivo evaluation with a rabbit anterior lamellar keratoplasty model showed that hydrogel/micelles platform could effectively inhibit corneal stromal fibrosis. This strategy achieves controlled and prolonged release of celastrol in the corneal stroma of rabbit. Following a single corneal interlamellar injection, celastrol effectively alleviated fibrosis via mTORC1 signal promoting autophagy and inhibiting TGF-ß1/Smad2/3 signaling pathway. Overall, this strategy demonstrates promise for the clinical application of celastrol in preventing corneal scarring and reducing corneal stromal fibrosis post-lamellar keratoplasty, highlighting the potential benefits of targeted drug delivery systems in ocular therapeutics.

Superlubricity Achieved by a Transparent Poly(vinylpyrrolidone) Composite Hydrogel with Glycerol Ethoxylate in Ocular Conditions.

Efficient and stable ocular lubrication is pivotal in safeguarding eye tissues from wear, especially under repetitive strain due to frequent blinking. Hydrogels have been reported to possess adjustable mechanical properties, biocompatibility, durability, and elevated water content and extensive utilization in medical fields. In this work, a kind of visible photo-cross-linking poly(vinylpyrrolidone) (PVP) hydrogel was designed and synthesized using 1-vinyl-2-pyrrolidone (NVP) and poly(ethylene glycol) diacrylate (PEGDA). To optimize the structure and improve the lubrication performance of hydrogels, we prepared and investigated glycerol ethoxylate (GE)-introduced composite hydrogels (GE/PVP). The results show that the addition of 3 wt % GE helped the hydrogel to form a uniform and dense porous matrix and reduce the frictional coefficient (COF) by over 50%, achieving superlubricity (COF ≈ 0.005). However, with the excessive increase of GE (6 wt %), the structure of the hydrogel is destroyed, inducing pore walls to thin and expand. After that, a lubrication mechanism of the GE/PVP composite hydrogel was proposed, in which the addition of GE reduced the surface tension of the hydrogel, enhanced the hydration ability of the hydrogel, and thus decreased the friction between sliding surfaces. Besides, the cytotoxicity tests show that the composite hydrogels possess good biocompatibility. Overall, the as-synthesized hydrogels hold great potential as lubricating medium for use in ocular applications.

Thermosensitive Triblock Copolymer for Slow-Release Lubricants under Ocular Conditions.

The ocular environment is crucial for a biological lubrication system. An unstable condition of tear film may cause a series of ocular diseases due to serious friction, such as dry eye syndrome, which has drawn extensive attention nowadays. In this study, an in vitro biocompatible superlubricity system, containing thermogelling copolymers (PCGA-PEG-PCGA) and slow-release lubricant (PEG 300/Tween 80), was constructed. First, the sol-gel transition temperature and gel strength of PCGA-PEG-PCGA were adjusted based on the ocular environment by regulating the length of PCGA blocks. Furthermore, the copolymer hydrogel exhibited a reliable slow-release property within 10 days and showed low cytotoxicity. Then, the superlubricity (coefficient of friction of approximately 0.005) was achieved with its released PEG 300/Tween 80 aqueous solution at the sliding velocity range of 1-100 mm s-1 and pressure range of 10-22 kPa. However, the lubrication behaviors varied, while PEG 300 chains and Tween 80 micelles were demonstrated to form a multilayer and a single layer adsorption structure on the sliding surface, respectively. On the whole, the composite lubrication systems, especially the one composed of Tween 80, showed excellent tribological properties owing to the stable slow-release and full hydration effects under ocular conditions, which hold great potential for improving ocular lubrication and maintaining human visual health.

Microfluidic Fabrication of Gelatin Acrylamide Microgels through Visible Light Photopolymerization for Cell Encapsulation.

Gelatin-based microgels are intriguing for various biomedical applications, which are conventionally prepared through photopolymerization of gelatin methacrylamide (GelMA). Here, we report on the modification of gelatin through acrylamidation to form gelatin acrylamide (GelA) with different substitution degrees, which was found to exhibit fast photopolymerization kinetics, better gelation, steady viscosity at elevated temperatures, and satisfying biocompatibility when compared to GelMA. By the online photopolymerization strategy with a home-made microfluidic setting, microgels of uniform sizes from GelA by blue light were obtained and their swollen properties were investigated. Compared to the microgels from GelMA, they showed an enhanced cross-linking degree and have better shape stability when swollen in water. Cell toxicities of the hydrogels from GelA and cell encapsulation from the corresponding microgels were investigated, which were found to exhibit superior properties than those from GelMA. We therefore believe that GelA has potential for constructing scaffolds for bioapplications and can be an excellent substitute for GelMA.

Dendronized Gelatin-Mediated Synthesis of Gold Nanoparticles.

Thermoresponsive dendronized gelatins (GelG1) or gelatin methacrylates (GelG1MA) were used as precursors to modulate the efficient reduction of Au(III) to form stable gold nanoparticles (AuNPs) through UV irradiation. These dendronized gelatins were obtained through the amidation of gelatin or gelatin methacrylates with dendritic oligoethylene glycols (OEGs). Crowded OEG dendrons along the gelatin backbones create a hydrophobic microenvironment, which promotes the reduction of Au(III). Gelatin backbones act as ligands through the electron-rich groups to facilitate the reduction, while the dendritic OEGs provide shielding effects through crowding to form a hydrophobic microenvironment, which not only enhances the reduction but also stabilize the formed AuNPs through encapsulation. The effects of dendron coverage on the dendronized biomacromolecules and their thermoresponsiveness on the reduction kinetics were examined. Dendronized gelatin/AuNPs hydrogels were further prepared through the in situ photo-crosslinking of GelG1MA. The modification of natural macromolecules through dendronization presented in this report facilitates a novel platform for the environmentally friendly synthesis of noble metal nanoparticles, which may form a new strategy for developing smart nano-biosensors and nano-devices.

Tailoring the Hydrophilicity for Delayed Condensation Frosting in Antifogging Coatings.

In the last few decades, numerous studies have focused on designing suitable hydrophilic materials to inhibit surface-induced fog or frost under extreme conditions. As fogging and condensation frosting on a film involves molecular interaction with water prior to forming discrete droplets on the surface, it is essential to control the extent of a film to strongly bind with water molecules for antifogging coatings. While the water contact angle measurement is commonly used to probe the hydrophilicity of a film, it oftentimes fails to predict the antifogging and antifrosting performance as this value only reflects the wettability of a given surface to water droplet. In this work, a polysaccharide-based film composed of chitosan (CHI) and carboxymethyl cellulose (CMC) is used as the model system and oligo(ethylene glycol) (OEG) moieties are additionally introduced to study the effect of OEG moieties on antifogging and condensation frosting. We show that the film containing OEG-grafted CHI exhibits excellent frost-resistant capability due to the OEG moieties in the film that serve as active sites for water molecules to strongly interact in a nonfreezable state.

Thermoresponsive dendritic oligoethylene glycols.

Monodispersed molecules of low molar masses showing thermoresponsiveness are appealing both for mechanism investigation of the thermally-modulated dehydration and aggregation on molecular levels and for designing functional intelligent materials. In the present report, thermoresponsive properties of a homologous series of monodispersed dendritic macromolecules carrying three-, four- or six-fold dendritic oligoethylene glycol (OEG) segments were investigated. These dendritic macromolecules carry either methoxyl or ethoxyl terminals, and have different cores (alcohol, methyl ester or methacryloyl) to exhibit different overall hydrophilicity. They show characteristic thermoresponsive properties with sharp phase transitions when suitable structural units are combined. Three structural factors determine their phase transition temperatures, including the cores, branching density and peripheral terminals. Thermally-induced collapse and aggregation are monitored with temperature-varied NMR spectroscopy at the microscale level and optical microscopy at the macroscale level. At elevated temperature, these dendritic macromolecules undergo fast exchange between the dehydrated and the hydrated states. These dendritic macromolecules afford structure-dependent confinement to guest dyes through their multi-valent interactions.

Thermoresponsive Supramolecular Assemblies from Dendronized Amphiphiles To Form Fluorescent Spheres with Tunable Chirality.

Balance between self-association of structural units and self-repulsion from crowding-induced steric hindrance accounts for the supramolecular assembly of the amphiphilic entities to form ordered structures, and solvation provides a toolbox to conveniently modulate the assemblies through differential interactions to various structural units. Here we report solvation-modulated supramolecular chiral assembly in aqueous solutions of amphiphilic dendronized tetraphenylethylenes (TPEs) with three-folded dendritic oligoethylene glycols (OEGs) through dipeptide Ala-Gly linkage. These dendronized amphiphiles can form supramolecular spheres with enhanced supramolecular chirality, which is tunable and dependent on solvation. These nanosized spherical aggregates exhibit thermoresponsive behavior, and their cloud point temperatures are dependent on mixed solvent of water and THF. The phase transition temperatures increase with water fractions due to water-driven shifting of OEG moieties from interiors of the aggregates to their peripheries. Furthermore, the thermally induced dehydration and collapse of OEG moieties mediate the reversible aggregation and deaggregation between the spheres, imparting tunable aggregation-induced fluorescent emission (AIE) and supramolecular chirality. Both experimental results and molecular dynamic simulations have highlighted that reversible chirality transformations of the amphiphilic dendronized assemblies mediated by solvation through change solvent quality or thermally dehydration are dependent on the balance between interactions of OEG dendrons with TPE moieties and with the solvent molecules.

Thermo-Gelling Dendronized Chitosans as Biomimetic Scaffolds for Corneal Tissue Engineering.

Biomimetic scaffolds with transparent, biocompatible, and in situ-forming properties are highly desirable for corneal tissue engineering, which can deeply fill corneal stromal defects with irregular shapes and support tissue regeneration. We here engineer a novel class of corneal scaffolds from oligoethylene glycol (OEG)-based dendronized chitosans (DCs), whose aqueous solutions show intriguing sol-gel transitions triggered by physiological temperature, resulting in highly transparent hydrogels. Gelling points of these hydrogels can be easily tuned, and furthermore, their mechanical strengths can be significantly enhanced when injected into PBS at 37 °C instead of pure water. In vitro tests indicate that these DC hydrogels exhibit excellent biocompatibility and can promote proliferation and migration of keratocyte. When applied in the rabbit eyes with corneal stromal defects, in situ formed DC hydrogels play a positive effect for new tissue regeneration. Overall, this thermo-gelling DCs possess appealing features as corneal tissue substitutes with their excellent biocompatibility and unprecedented thermoresponsiveness.

Upper Critical Solution Temperature-Type Responsive Cyclodextrins with Characteristic Inclusion Abilities.

Water-soluble and thermoresponsive macrocycles with stable inclusion toward guests are highly valuable to construct stimuli-responsive supramolecular materials for versatile applications. Here, we develop such macrocycles - ureido-substituted cyclodextrins (CDs) which exhibit unprecedented upper critical solution temperature (UCST) behavior in aqueous media. These novel CD derivatives showed good solubility in water at elevated temperature, but collapsed from water to form large coacervates upon cooling to low temperature. Their cloud points are greatly dependent on concentration and can be mediated through oxidation and chelation with silver ions. Significantly, the amphiphilicity of these CD derivatives is supportive to host-guest binding, which affords them inclusion abilities to guest dyes. The inclusion complexation remained nearly intact during thermally induced phase transitions, which is in contrast to the switchable inclusion behavior of lower critical solution temperature (LCST)-type CDs. Moreover, ureido-substituted CDs were exploited to co-encapsulate a pair of guest dyes whose fluorescence resonance energy transfer process can be switched by the UCST phase transition. We therefore believe these novel thermoresponsive CDs may form a new strategy for developing smart macrocycles and allow for exploring smart supramolecular materials.

Multiple-Responsive Dendronized Hyperbranched Polymers.

By combining topological structures of hyperbranched polymers with dendronized polymers, a series of hyperbranched poly(acylhydrazone)s pendanted with 3-fold branched dendritic oligoethylene glycol (OEG) units were efficiently prepared through A2 + B3 polycondensation. The constituents of these dendritic polymers can be mediated through dynamic covalent acylhydrazones. Owing to the dense OEG pendants, these dendronized hyperbranched polymers are biocompatible and thermoresponsive, and their cloud points (T cps) can be modulated by the branched architecture, solution pH, and addition of a third component. Cell viability in the presence of these hyperbranched poly(acylhydrazone)s can be maintained above 80%. Based on the unique dendritic architecture with rich acylhydrazine groups, dynamic hydrogels cross-linked via acylhydrazone linkages with good mechanical property were prepared, which inherit the characteristic thermoresponsive behavior of the polymer precursors and also show remarkable self-healing properties. This novel kind of topological polymers and their corresponding hydrogels with dynamic and multiple smart properties may have promising applications as biomaterials.

Thermoresponsive double network cryogels from dendronized copolymers showing tunable encapsulation and release of proteins.

A series of double-network cryogels (DNCs) were prepared from oligoethylene glycol (OEG)-based dendronized copolymers as the first network and polyvinyl alcohol (PVA) as the second network. The dendronized copolymers were composed of dendritic OEG units, as well as triethoxysilyl, amine or carboxyl groups. The dendritic OEGs ensured characteristic thermoresponsiveness and triethoxysilyl groups were for crosslinking, while amino and carboxyl groups were designed to provide charged species for specifically interacting with proteins. PVA behaves as a mutual support which ensures the stability and mechanical properties of the cryogels. These DNCs exhibited good thermoresponsiveness and biocompatibility. Upon increasing the temperature above their cloud points (Tcps), the cryogels became dehydrated with enhanced hydrophobicity, and thus their porous structures shrank. This property was utilized to mediate encapsulation and release of proteins. The loading and release efficiencies of different proteins were found to be dominated by hydrophilic to hydrophobic transitions of the first network, and at the same time, by the properties of proteins. At room temperature, the cryogel could efficiently capture model proteins, while above Tcps, more than 80% of lysozyme could be released in 24 h with enzyme activity remaining unchanged. These series of smart cryogels based on thermoresponsive dendronized copolymers may provide promising applications for the reversible capture of enzymes or proteins.

Effects of different scaffolds on rat adipose tissue derived stroma cells.

BACKGROUND: Adipose tissue derived stroma cells (ASC's) offer for many advantages for tissue engineering strategies over mesenchymal stroma cells from other sources and ideal carrier materials have to be identified for them. The aim of this study was to demonstrate and to compare the effects of three clinically established biomaterials on proliferation and metabolic activity of rat ASC's in vitro. MATERIALS AND METHODS: Rat adipose tissue derived stroma cells (ASC's) were isolated and differentiated into distinct lineages proved by lineage specific staining and gene expression analysis (RT-PCR). The biomaterials Bio-Gide(®), Tutodent(®) Membrane and Belotero(®) Soft were tested with rat ASC's for their biocompatibility using scanning electron microscopy (SEM), cell vitality staining, cytotoxicity and proliferation tests (LDH, MTT, BrdU, WST-1). RESULTS: The collagen membrane Bio-Gide(®) resulted in a significantly higher viability and proliferation (WST-1, BrdU) compared to Tutodent(®) Membrane. No significant difference was determined in the LDH and MTT test. The hyaluronic acid gel Belotero(®) Soft showed no cytotoxicity (LDH, FDA/PI) and had no negative effects on metabolic activity (WST-1, MTT) or cell proliferation (BrdU) of ASC's. CONCLUSION: Our results indicate Bio-Gide(®) and Belotero(®) Soft as preferable carrier materials for ASC's. For the further establishment of ASC's-based treatment strategies, in vivo investigations on the tissue regeneration potential of these cell-biomaterial scaffolds should follow.