Hydrogels are required to have high mechanical properties, biocompatibility, and an easy fabrication process for biomedical applications. Double-network hydrogels, although strong, are limited because of the complicated preparation steps and toxic materials involved. In this study, we report a simple method to prepare tough, in situ forming polyethylene glycol (PEG)–agarose double-network (PEG–agarose DN) hydrogels with good biocompatibility. The hydrogels display excellent mechanical strength. Because of the easily in situ forming method, the resulting hydrogels can be molded into any form as needed. In vitro and in vivo experiments illustrate that the hydrogels exhibit satisfactory biocompatibility, and cells can attach and spread on the hydrogels. Furthermore, the residual amino groups in the network can also be functionalized for various biomedical applications in tissue engineering and cell research.Keywords: agarose; biocompatible; double network; hydrogels; PEG;

Implant-associated infections in orthopaedic surgeries are very critical as they may hinder bone healing, cause implant failure and even progress to osteomyelitis. Drug-eluting implants for local delivery of antibiotics at surgical sites are thought to be promising in preventing infections. Herein, the antibiotic vancomycin was encapsulated in a poly(ethylene glycol) (PEG)-based hydrogel film that was covalently bound to Ti implants and subsequently covered by a PEG-poly(lactic-co-caprolactone) (PEG-PLC) membrane. Additionally, crosslinked starch (CSt) was mixed with the hydrogel because its porous microstructure is able to inhibit hydrogel swelling and thus slow down drug release. The release behavior could be regulated by the drug loading and the coating thickness. The vancomycin-loaded Ti implants showed no initial burst release, offering a sustained drug release for nearly 3 weeks in vitro and more than 4 weeks in vivo. In a rabbit model of S. aureus infection, the implants with a 4 mg vancomycin loading significantly reduced the inflammatory reaction and exhibited a good antimicrobial capability. The immobilization of the antibiotic-loaded polymeric coatings on orthopaedic implants can offer a sustainable drug release with no initial burst release and maintain an effective concentration for a longer time, so it is expected to be an effective strategy to treat and prevent local bone infections.

Currently, the major issues in the treatment of osteoarticular tuberculosis (TB) after implant placement are low drug concentration at the infected focus and drug resistance resulting from the long-term chemotherapy. The application of drug-loaded polymeric multilayers on implantable devices offers a promising solution to the problems. Herein, a poly(ethylene glycol)-based hydrogel film embedded with isoniazid (INH)-loaded alginate microparticles was fixed to Ti implants via adhesive polydopamine, subsequently capped by poly(lactic-co-glycolic acid) membranes for the sustained and localized delivery of the anti-TB drug. The antibacterial efficacy of the released INH was confirmed by a 4.5 ± 0.8 cm inhibition zone formed in the fourth week after inoculation of Mycobacterium tuberculosis. The INH-loaded Ti implants showed no toxicity to the osteoblast cell and provided a consistent drug release for nearly one week in vitro. The release profile in vivo showed a high local concentration and low systemic exposure. The local INH concentration could be kept higher than its minimum inhibitory concentration over a period of 8 weeks, which proves that it is a promising strategy to improve the severe osteoarticular TB treatment.

In recent years, hydroxyapatite (HAp) and β-tricalcium phosphate (TCP) were extensively used to prepare composite scaffolds for bone repair. However, due to a lack of systematical evaluation of HAp and TCP composite scaffolds for bone repair, their distinctions on bone regeneration in vivo have not been clearly clarified to date. In this study, we constructed HAp and TCP composite poly(lactic-co-glycolic acid) (PLGA) scaffolds with the same contents of HAp and TCP and similar structures and porosities, and systematically investigated their performance in the repair of rabbits’ calvarial bone defects. The HAp/PLGA scaffold possessed stronger mechanical property and higher cell proliferation than the TCP/PLGA scaffold, endowing it with better performance of bone regeneration at an early stage. Since TCP could greatly neutralize degraded acidic products and be slowly absorbed in vivo to release occupied room for new bone growth compared to HAp, the TCP/PLGA scaffold yielded more intact new bone for long-term repair of the defects. Our results clearly demonstrate that TCP is a superior bioceramic for bone tissue engineering, showing promise for the perfect repair of bone defects via tissue engineering.

Motivated by the demand for high-performance soft materials for applications in catalysis, drug delivery and biomedical materials, the development of smart hydrogels that possess both biocompatibility and stimulus responsiveness has been highly desirable. Here, we demonstrated a facile method to construct a multi-responsive supramolecular hydrogel by the formation of host–guest complexes between the tadpole-shaped PEG-POSS-(CD)7 polymer and Azo-SS-Azo dimer. Incorporation of rigid POSS units furnished supramolecular cross-linked networks with high mechanical strength. The reversible gel–sol phase transition of supramolecular hydrogels could be induced by temperature, light and redox while the Azo derivatives could induce a quick gel–sol transition. These novel supramolecular hydrogels also possessed a favorable self-healing ability and better biocompatibility, which endowed the smart hydrogels with potential practical and real-life applications that will be beneficial for further development of more intelligent materials with desired functionalities.

PEG-related adhesives are limited in clinical use because they are easy to swell and cannot support the cell growth. In this study, we produced a series of POSS-modified PEG adhesives with high adhesive strength. Introduction of inorganic hydrophobic POSS units decreased the swelling of the adhesives and enhanced cell adhesion and growth. The in vitro cytotoxicity and in vivo inflammatory response experiments clearly demonstrated that the adhesives were nontoxic and possessed excellent biocompatibility. Compared with the sutured wounds, the adhesive-treated wounds showed an accelerated healing process in wounded skin model of the Bama miniature pig, demonstrating that the POSS-modified PEG adhesive is a promising candidate for wound closure.

Inspired by the highly ordered nanostructure of bone, nanodopant composite biomaterials are gaining special attention for their ability to guide bone tissue regeneration through structural and biological cues. However, bone malformation in orthopedic surgery is a lingering issue, partly due to the high surface energy of traditional nanoparticles contributing to aggregation and inhomogeneity. Recently, carboxyl-functionalized synthetic polymers have been shown to mimic the carboxyl-rich surface motifs of non-collagenous proteins in stabilizing hydroxyapatite and directing intrafibrillar mineralization in-vitro. Based on this biomimetic approach, it is herein demonstrated that carboxyl functionalization of poly(lactic-co-glycolic acid) can achieve great material homogeneity in nanocomposites. This ionic colloidal molding method stabilizes hydroxyapatite precursors to confer even nanodopant packing, improving therapeutic outcomes in bone repair by remarkably improving mechanical properties of nanocomposites and optimizing controlled drug release, resulting in better cell in-growth and osteogenic differentiation. Lastly, better controlled biomaterial degradation significantly improved osteointegration, translating to highly regular bone formation with minimal fibrous tissue and increased bone density in rabbit radial defect models. Ionic colloidal molding is a simple yet effective approach of achieving materials homogeneity and modulating crystal nucleation, serving as an excellent biomimetic scaffolding strategy to rebuild natural bone integrity.

•A facile method to fabricate the pH-responsive vesicle with AIE features based on a tadpole-shaped PEG750-POSS-(TPE)7 polymer.•Incorporation of the rigid cage-shaped POSS units to highly restrict TPE intramolecular rotation and powerfully improve AIE effects in aggregate state.•A unique shape-transformation from homogenous vesicles to spherical TPE NPs by acid-induced decomposition-assembly process.•A controlled size-growth of the TPE NPs by manipulation of acid soaking time.•Good compatibility and excellent photostability of AIE-active TPE NPs for long-term live cell imaging.Self-assembly schemes provide a simple and tunable approach to creating a myriad of well-defined nanostructures from design of macromolecules in bulk, thin film and solution environments. Here we demonstrated a facile method to construction of tetraphenylethylene nanoparticles (TPE NPs) by decomposition-assembly from pH-responsive and AIE-characteristic vesicles, which were self-assembled by an amphiphilic PEG750-POSS-(TPE)7 polymer in aqueous solutions. The introduction of Schiff base bonds furnished the fluorescent polymersomes with unique pH responsiveness that is stable under physiological conditions but quickly degradable in acidic environments. Interestingly, the luminous vesicles were transformed into spherical TPE NPs in a solution of lower pH on account of the synergetic combination of cleavage rate of the Schiff base bonds and guidance effect of the entangled tadpole-shaped polymeric chains. The AIE feature of TPE molecule was completely retained in the TPE NPs. Compared to the pH-responsive PEG750-POSS-(TPE)7 vesicles, these AIE-active TPE NPs possessed stable morphology and adjustable size by manipulation of the incubation time. These TPE NPs can be quickly internalized into the tumors through endocytosis pathway and retain strong blue luminescence inside the living cells for a long period, presenting the good photostability and biological imaging property. Cytotoxicity assay revealed that TPE NPs were biocompatible and thus can be utilized for long-term live cell imaging and biomedical applications.Download high-res image (385KB)Download full-size image

Recently, nanoparticles self-assembled from amphiphilic supramolecular linear-dendritic block copolymers (LDBCs) have attracted great interest, since the combination of linear and dendritic polymers can incorporate the unique properties of the different segments but avoid some inherent drawbacks of dendrimers, not to mention that the components can be flexibly adjusted to enrich their functionality. In this study, LDBCs formed by host–guest recognition of polyacetal dendrimers with a β-cyclodextrin core and adamantane-terminated zwitterionic poly(sulfobetaine) could self-assemble into micelles and vesicles by varying the hydrophilic/hydrophobic ratio. Owing to the acid-labile characteristic of the dendritic segments, the micelles and vesicles were degradable and could release their payloads in a pH-responsive manner. The incorporation of zwitterionic linear segments gave the micelles and vesicles a charge-reversal ability and excellent resistivity to protein absorption, leading to higher affinity to cell membranes than conventional PEG-coated nanoparticles. In addition, the potential of these nanoparticles as anticancer drug carriers was preliminarily evaluated by using doxorubicin as a model drug and the results indicated that the DOX-loaded micelles and vesicles exhibited remarkable anticancer activity. This study cast a new light on the application of dendrimers and these micelles and vesicles constructed from LDBCs may be promising candidates as anticancer drug delivery platforms for cancer therapy.

Immediate hemorrhage control and infection prevention are pivotal for saving lives in critical situations such as battlefields, natural disasters, traffic accidents, and so on. In situ hydrogels are promising candidates, but their mechanical strength is often not strong enough for use in critical situations. In this study, we constructed three hydrogels with different amounts of Schiff-base moieties from 4-arm-PEG-NH2, 4-arm-PEG-NHS, and 4-arm-PEG-CHO in which vancomycin was incorporated as an antimicrobial agent. The hydrogels possess porous structures, excellent mechanical strength, and high swelling ratio. The cytotoxicity studies indicated that the composite hydrogel systems possess good biocompatibility. The Schiff bases incorporated improve the adhesiveness and endow the hydrogels with bacteria-sensitivity. The in vivo hemostatic and antimicrobial experiments on rabbits and pigs demonstrated that the hydrogels are able to aid in rapid hemorrhage control and infection prevention. In summary, vancomycin-loaded hydrogels may be excellent candidates as hemostatic and antibacterial materials for first aid treatment of the wounded in critical situations.

We demonstrate a facile approach to constructing aggregation induced emission (AIE) fluorescent vesicles assembled using a PEG–POSS–(TPE)7 polymer. The narrow wall thickness provides an ideal confined space for creating fluorescence resonance energy transfer (FRET) systems between TPE donors and encapsulated FITC or DOX acceptors.

Cationic polymer vectors have received increasing attention for gene delivery in biotechnology over the past 2 decades, but few polymer vectors were used in clinical applications due to their low gene transfection efficacy. One of the major reasons is that the conventional cationic polymers can induce the increasing of intracellular reactive oxygen species (ROS) concentration and oxidative stress, which reduces the gene transfection efficacy. Here, we create a novel class of thioether dendron-branched polymer conjugate and self-assemble this conjugate into bioreducible cationic nanomicelles with disulfide bond connecting the thioether core to the cationic shell. The obtained nanomicelles have a unique ROS self-scavenging ability, thereby dramatically improving gene transfection efficacy.Keywords: bioreducible nanomicelles; gene delivery; reactive oxygen species; self-assemble; self-scavenge

We report a method of utilizing a UV-triggered thiol–disulfide exchange reaction for constructing biodegradable hydrogels with tailored properties from a water-soluble comb-like polymer of P(EMA-SS-PEG), a polyethylene glycol grafted poly(ethyl methacrylate) derivative with the disulfide linkage as the grafting point. This photochemical method provides precise spatiotemporal control over the structures and properties of disulfide-crosslinked hydrogels. By varying the irradiation time, we facilely adjust the crosslinking degree of hydrogels, thereby regulating their morphology, mechanical properties, hydrophilic properties, and swelling ratio. The photochemical method can easily fabricate macro-/micro-customized patterned hydrogels, indicating its precise spatial control on the photochemical gelation process. In addition, the tailor-made biodegradable hydrogels can achieve tunable absorption and release behaviors of RB dyes, proving their potential application in controlled drug delivery.

•Starch microcapsules were used as low-cost carriers for the release of pesticides.•Starch microcapsules were mass produced and favorable for practical application.•The size of microcapsules were uniform and easily adjustable.•The release behavior could be tuned by particle size and drug content.In recent years, starch microparticles have gained interest in many fields. However, low production, uncontrollable size, and varying size distribution hinder their practical application. Here, we adopt a premix membrane emulsification (PME) method to prepare starch microcapsules at high production rates. The process conditions were optimized to fabricate uniform microcapsules with controllable sizes and narrow size distribution (PDI < 0.1). Through encapsulating avermectin (Av), a kind of water-insoluble pesticide, into the shell of the microcapsules in situ during the process, we developed a pesticide delivery system that enabled a controlled and consistent release of Av over a period of 2 weeks. Kinetic analysis indicated that the mechanisms of Av release involved non-Fickian and Case-II transport. The diameters (0.70–4.8 μm) of the microcapsules and Av contents (16–47%) were adjusted to achieve suitable release profiles. The results will lay the foundation for further field experiments.

Controlled porous structures, adjustable surface properties and good mechanical properties are essential for hydrogels in promoting cell adhesion and growth. In this work, we developed four armed poly(ethylene glycol) (4-arm-PEG) hydrogels crosslinked by poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs). Branched polyethyleneimine (b-PEI) was employed for aminolysis of PLGA to engineer 300, 530 and 1000 nm NPs with a nitrogen contents of 11.7%, 9.4% and 9.7%. Hybrid hydrogels were formed by crosslinking amino-packed NPs with polymeric chains of 4-arm-PEG-NHS. By manipulating the NP and PEG contents as well as the NP sizes, the pore sizes could be tailored from 10–20 μm to 20–40 μm and 100–200 μm, and the maximal compressive strength could be optimized to 0.37 MPa. Cytotoxicity trials indicated the hydrogels were almost non-toxic and biocompatible. Cell adhesion evaluation testified higher amino contents and a smaller proportion of PEG led to more cell attachment. These results demonstrated that this kind of hybrid hydrogel may be a suitable candidate for further biomedical applications in tissue engineering.

Here we demonstrate a type of pH and reduction dual-sensitive biodegradable micelles, which were self-assembled by a cationic polymer in an aqueous solution. Due to tumor cells or tissues showing low pH and high reduction concentration, these micelles possessed specific tumor targetability and maximal drug-release controllability inside tumor cells upon changes in physical and chemical environments, but presented good stability at physiological conditions. CCK-8 assay showed that the DOX-loaded micelles had a similar cytotoxicity for MCF-7 tumor cells as free DOX, and blank micelles had a very low cytotoxicity to the cells. Fluorescent microscopy observation revealed that the drug-loaded micelles could be quickly internalized by endosomes to inhibit cancer cell growth. These results indicated these biodegradable micelles, as a novel and effective pH- and redox-responsive nanocarrier, have a potential to improve drug delivery and enhance the antitumor efficacy.

Michael addition polymerizations of amines and acrylic monomers are versatile approaches to biomaterials for various applications. A combinatorial library of poly(β-amino ester)s and diverse poly(amido amine)s from diamines and diacrylates or bis(acrylamide)s have been reported, respectively. Furthermore, novel linear and hyperbranched polymers from Michael addition polymerizations of trifunctional amines and acrylic monomers significantly enrich this category of biomaterials. In this Review, we focus on the biomaterials from Michael addition polymerizations of trifunctional amines and acrylic monomers. First we discuss how the polymerization mechanisms, which are determined by the reactivity sequence of the three types of amines of trifunctional amines, i.e., secondary (2°) amines (original), primary (1°) amines, and 2° amines (formed), are affected by the chemistry of monomers, reaction temperature, and solvent. Then we update how to design and synthesize linear and hyperbranched polymers based on the understanding of polymerization mechanisms. Linear polymers containing 2° amines in the backbones can be obtained from polymerizations of diacrylates or bis(acrylamide)s with equimolar trifunctional amine, and several approaches, e.g., 2A2+BB′B″, A3+2BB′B′, A2+BB′B″, to hyperbranched polymers are developed. Further through molecular design of monomers, conjugation of functional species to 2° amines in the backbones of linear polymers and the abundant terminal groups of hyperbranched polymers, the amphiphilicity of polymers can be adjusted, and additional stimuli, e.g., thermal, redox, reactive oxidation species (ROS), and light, responses can be integrated with the intrinsic pH response. Finally we discuss the applications of the polymers for gene/drug delivery and bioimaging through exploring their self-assemblies in various motifs, e.g., micelles, polyplexes particles/nanorings and hydrogels. Redox-responsive hyperbranched polymers can display 300 times higher in vitro gene transfection efficiency and provide a higher in vivo siRNA efficacy than PEI. Also redox-responsive micelle carriers can improve the efficacy of anticancer drug and the bioimaging contrast. Further molecular design and optimization of this category of polymers together with in vivo studies should provide safe and efficient biomaterials for clinical applications.

A series of telechelic supramolecular amphiphiles [POSS–Azo8@(β-CD–PDMAEMA)1→8] was accomplished by orthogonally coupling the multiarm host polymer β-cyclodextrin–poly(dimethylaminoethyl methacrylate) (β-CD–PDMAEMA) with an octatelechelic guest molecule azobenzene modified-polyhedral oligomeric silsesquioxanes (POSS–Azo8) under different host–guest ratios. These telechelic supramolecular amphiphiles possess a rigid core and flexible corona. Increasing the multiarm host polymer coupled onto the rigid POSS core made the molecular architecture tend to be symmetrical and spherical. POSS–Azo8@[β-CD–PDMAEMA]1→8 could self-assemble into diverse morphologies evolving from spherical micelles, wormlike micelles, and branched aggregates to bowl-shaped vesicles. Distinct from the traditional linear amphiphilic polymers, we discovered that the self-assembly of POSS–Azo8@[β-CD–PDMAEMA]1→8 was dominantly regulated by their molecular architectures instead of hydrophilicity, which has also been verified using computer simulation results.

•An aqueous microcapsule formulation was yielded via premix membrane emulsification.•The loading content of Lambda–Cyhalothrin was higher than 40%.•The sizes of microcapsule systems were tunable from 0.68 to 4.6 μm.•The stable microcapsule formulation showed high efficacy on plutella xylostella.Conventional pesticides usually need to be used in more than recommended dosages due to their loss and degradation, which results in a large waste of resources and serious environmental pollution. Encapsulation of pesticides in biodegradable carriers is a feasible approach to develop environment-friendly and efficient controlled-release delivery system. In this work, we fabricated three kinds of polylactic acid (PLA) carriers including microspheres, microcapsules, and porous microcapsules for controlled delivery of Lambda–Cyhalothrin (LC) via premix membrane emulsification (PME). The microcapsule delivery system had better water dispersion than the other two systems. Various microcapsules with a high LC contents as much as 40% and tunable sizes from 0.68 to 4.6 μm were constructed by manipulating the process parameters. Compared with LC technical and commercial microcapsule formulation, the microcapsule systems showed a significantly sustained release of LC for a longer period. The LC release triggered by LC diffusion and matrix degradation could be optimally regulated by tuning LC contents and particle sizes of the microcapsules. This multi-regulated release capability is of great significance to achieve the precisely controlled release of pesticides. A preliminary bioassay against plutella xylostella revealed that 0.68 μm LC-loaded microcapsules with good UV and thermal stability exhibited an activity similar to a commercial microcapsule formulation. These results demonstrated such an aqueous microcapsule delivery system had a great potential to be further explored for developing an effective and environmentally friendly pesticide-release formulation.

Here we have demonstrated a facile method for construction of self-assembled nanoparticles with excellent fluorescent properties by the synergetic combination of unique AIE effects and tadpole-shaped polymers. The introduction of acid-sensitive Schiff base bonds furnished the polymeric vesicles and micelles with unique pH responsiveness that can possess maximal drug-release controllability inside tumor cells upon changes in physical and chemical environments, but present good stability under physiological conditions. Having benefited from the efficient fluorescence resonance energy transfer (FRET), the DOX-loaded fluorescent aggregates were employed for intracellular imaging and self-localization in surveillance of systemic DOX delivery. Cytotoxicity assay of the DOX-loaded aggregates indicated a fast internalization and a high cellular proliferation inhibition to MCF-7 cells while the PEG-POSS-(TPE)7 nanoparticles displayed no cytotoxicity, exhibiting excellent biocompatibility and biological imaging properties. These results indicated that these biodegradable nanoparticles, as a class of effective pH-responsive and visible nanocarriers, have the potential to improve smart drug delivery and enhance the antitumor efficacy for biomedical applications.

An ideal tissue engineering scaffold should imitate physical and biochemical cues of natural extracellular matrix and have interconnected porous structures with high porosity to provide adequate space for cell seeding, growth and proliferation, as well as nutrient delivery and metabolized product elimination. In this study, we examined the feasibility of fabricating microtubule-orientated poly(lactide-co-glycolide) (PLGA) scaffolds with interconnected pores (denoted as MOIP-PLGA) by an improved thermal-induced phase separation technique. We successfully constructed MOIP-PLGA using 1,4-dioxane as the first solvent and benzene or water with lower freezing point as the second solvent. Especially, when water was used, the MOIP-PLGA had higher porosity and it could guide rabbit aortic smooth muscle cells (SMCs) to better grow along the microtubule direction of the scaffold. Comparing with microtubule-orientated scaffold without interconnected pores (denoted as MONIP-PLGA), the proliferation and viability of SMCs cultured on MOIP-PLGA were higher. Moreover, basic fibroblast growth factor could be effectively bound on MOIP-PLGA by a plasma treatment technique and the growth factor could be slowly released in vitro, maintaining bioactivity.

Here we demonstrate a simple and straightforward approach to prepare POSS-embedded hyperbranched (HB-POSS) polymers with customized molecular weights and sizes just by controlling the polymerization time. The polymers can be further used for building amphiphilic polymers, presenting morphological transition from micelle to vesicle in aqueous solution.

It was recently reported that ethanolamine-functionalized poly(glycidyl methacrylate) (PGEA) possesses great potential applications in gene therapy due to its good biocompatibility and high transfection efficiency. Importing responsivity into PGEA vectors would further improve their performances. Herein, a series of responsive star-shaped vectors, acetaled β-cyclodextrin-PGEAs (A-CD-PGEAs) consisting of a β-CD core and five PGEA arms linked by acid-labile acetal groups, were proposed and characterized as therapeutic pDNA vectors. The A-CD-PGEAs owned abundant hydroxyl groups to shield extra positive charges of A-CD-PGEAs/pDNA complexes, and the star structure could decrease charge density. The incorporation of acetal linkers endowed A-CD-PGEAs with pH responsivity and degradation. In weakly acidic endosome, the broken acetal linkers resulted in decomposition of A-CD-PGEAs and morphological transformation of A-CD-PGEAs/pDNA complexes, lowering cytotoxicity and accelerating release of pDNA. In comparison with control CD-PGEAs without acetal linkers, A-CD-PGEAs exhibited significantly better transfection performances.Keywords: acetal linker; acid-lability; biodegradation; gene vector; star-shaped;

Well-designed agents for enhanced multimodal imaging have attracted great interests in recent years. In this work, we adopted a premix membrane emulsification (PME) method to prepare uniform PEGylated poly(lactic-co-glycolic acid) (PLGA) microcapsules (MCs) with superparamagnetic Fe3O4 nanoparticles (NPs) embedded in the shell (Fe3O4@PEG–PLGA MCs) for ultrasound (US)/magnetic resonance (MR) bimodal imaging. Compared to Fe3O4@PLGA MCs without PEGylation, Fe3O4@PEG–PLGA MCs could more stably and homogeneously disperse in physiological solutions. In vitro and in vivo trials demonstrated that Fe3O4@PEG–PLGA MCs (∼3.7 μm) with very narrow size distribution (PDI = 0.03) could function as efficient dual-modality contrast agents to simultaneously enhance US and MR imaging performance greatly. In vitro cell toxicity and careful histological examinations illustrated no appreciable cytotoxicity and embolism of Fe3O4@PEG–PLGA MCs to mice even at high dose. The uniform composite MCs developed here can act as clinical bimodal contrast agents to improve hybrid US/MR imaging contrast, which is promising for accurate diagnosis and real-time monitoring of difficult and complicated diseases.Keywords: contrast agents; Fe3O4 nanoparticles; magnetic resonance imaging; PEG−PLGA microcapsules; ultrasound imaging

Herein, we report a feasible method to prepare a tadpole-shaped PEG-POSS-(Azo)7 polymer. The polymer self-assembled into a large vesicle in aqueous solution, undergoing reversible smooth-curling transformation responsive to UV and dark conditions. Incorporating POSS units into the azopolymer furnished quick trans–cis isomerization along a cubic orientation. The orientational isomerization formed some pores on the vesicular membrane and endowed the highly sensitive photoresponsive property. Encapsulation of various fluorescent dyes affected the hydrophilic/hydrophobic ratio of self-assemblies, causing their morphological transition from vesicles to micelles. Response to UV irradiation, the quick trans–cis isomerization resulted in rapid release of the encapsulated dyes. The intriguing photoresponsive property renders this kind of tadpole-shaped POSS hybrid azopolymer a potential for application in controlled release of drug.

Three types of azobenzene-based telechelic guest polymers, PEG-azo, azo-PEG-azo, and PEG-azo4, were synthesized by a facile method. Subsequently, a series supramolecular amphiphiles with three distinct topological structures (hemitelechelic, ditelechelic, and quadritelechelic) were constructed through coupling with host polymer β-cyclodextrin-poly(l-lactide) (β-CD-PLLA) by combined host–guest complexation. Research on the self-assembly behavior of these amphiphiles demonstrated that the variation in self-assembly was tuned by the synergistic interaction of hydrophilicity and the curvature of the polymer chains, and very importantly, the topological structure of amphiphiles demonstrated effective control of the self-assembly behavior.

Here, we demonstrate the first known approach to create G1 and G2 POSS dendrimers with 9 and 65 POSS units, and 56 and 392 terminal vinyl groups from a 1 → 7 branching monomer in only one and three steps.

The bioreducible star-shaped gene vector (POSS-(SS-PDMAEMA)8) with well-defined structure and relatively narrow molecular weight distribution was synthesized via atom transfer radical polymerization (ATRP) of (2-dimethylamino)ethyl methacrylate (DMAEMA) from a polyhedral oligomeric silsesquioxane (POSS) macroinitiator. POSS-(SS-PDMAEMA)8 was composed of a biocompatible POSS core and eight disulfide-linked PDMAEMA arms, wherein the PDMAEMA chain length could be adjusted by controlling polymerization time. POSS-(SS-PDMAEMA)8 can effectively bind pDNA into uniform nanocomplexes with appropriate particle size and zeta potential. The incorporation of disulfide bridges gave the POSS-(SS-PDMAEMA)8 material facile bioreducibility. In comparison with POSS-(PDMAEMA)8 without disulfide linkage, POSS-(SS-PDMAEMA)8 exhibited much lower cytotoxicity and substantially higher transfection efficiency. The present work would provide useful information for the design of new POSS-based drug/gene carriers.Keywords: bioreducible; disulfide bond; gene transfection; POSS; vector;

An ultrasound contrast agent (UCA) plays a key role in ultrasound imaging to precisely diagnose coronary heart disease. Microcapsules composed of inner gas and shell materials are most commonly employed as ultrasound contrast agents. The ultrasonic properties of the microcapsules are significantly dependent on their size and size distribution. Herein, we prepared several uniform sized biodegradable polylactone microcapsules by combining a premix membrane emulsification technique and W/O/W method. We investigated various size-dependent factors to optimize the size and size distribution of the microcapsules. After evaluation for ultrasound imaging, ∼4 μm PLLA (poly(L-lactide)) microcapsules generated more intense ultrasound signals than PLGA7030 or PLGA5050 (poly(lactic-co-glycolic acid), the molar ratio of lactic acid and glycolic acid being 70:30 or 50:50), PEG-b-PLGA7030 (poly(ethylene glycol)-block-poly(lactic-co-glycolic acid)), PLC5050 (poly(L-lactide-co-caprolactone), the molar ratio of lactide and caprolactone being 50:50) and PEG-b-PLLA microcapsules. The signal duration of the PLLA and PEG-PLLA microcapsules could reach ca. 3 and 3.5 min continuously. The ultrasound signal intensity and duration of the signals of PLLA microcapsules were considerably stronger and longer than those of commercially available UCAs, showing that the PLLA microcapsules have a great potential as more efficient UCAs for biomedical imaging.

A star polymer, β-cyclodextrin-poly(l-lactide) (β-CD–PLLA), and a linear polymer, azobenzene–poly(ethylene glycol) (Azo–PEG), could self-assemble into a supramolecular amphiphilic copolymer (β-CD–PLLA@Azo–PEG) based on the host–guest interaction between β-CD and azobenzene moieties. This linear-star supramolecular amphiphilic copolymer further self-assembled into a variety of morphologies, including sphere-like micelle, carambola-like micelle, naan-like micelle, shuttle-like lamellae, tube-like fiber, and random curled-up lamellae, by tuning the length of hydrophilic or hydrophobic chains. The variation of morphology was closely related to the topological structure and block ratio of the supramolecular amphiphiles. These self-assembly structures could disassemble upon an ultraviolet (UV) light irradiation.

A controlled cross-linking strategy is reported for producing inorganic–organic hybrid hydrogels with tunable properties from a disulfide-linked core/shell precursor with a polyhedral oligomeric silsesquioxane (POSS) core and polyethylene glycol (PEG) shells. The strategy also creates a new approach to fabricating macroscopic nanostructured inorganic materials from direct conversion of hybrid hydrogels.

A general approach to controlled formation of microgels/nanogels is developed for producing hydrogel particles with customizable structures and properties, especially for fabricating multilayered hydrogel particles with flexibly designable structures and properties of each layer. An inverse emulsion technique is adopted to obtain micro- or nanodroplets of a disulfide-linked core/shell hyperbranched polymer. Then pH of the droplets is manipulated to trigger and control in situ core/shell separation of the polymer, dissociation of the shells, and cross-linking of the cores, in the confined space at micro/nanoscales. Loose and compact microgels/nanogels with diverse properties like particle size and swelling capacity are yielded via adjusting the gelation time. Multilayered hydrogel particles with each tailor-made layer are further prepared using the controlled in situ gelation method in association with a seed emulsion technique.

Currently, the major issues in the treatment of osteoarticular tuberculosis (TB) after implant placement are low drug concentration at the infected focus and drug resistance resulting from the long-term chemotherapy. The application of drug-loaded polymeric multilayers on implantable devices offers a promising solution to the problems. Herein, a poly(ethylene glycol)-based hydrogel film embedded with isoniazid (INH)-loaded alginate microparticles was fixed to Ti implants via adhesive polydopamine, subsequently capped by poly(lactic-co-glycolic acid) membranes for the sustained and localized delivery of the anti-TB drug. The antibacterial efficacy of the released INH was confirmed by a 4.5 ± 0.8 cm inhibition zone formed in the fourth week after inoculation of Mycobacterium tuberculosis. The INH-loaded Ti implants showed no toxicity to the osteoblast cell and provided a consistent drug release for nearly one week in vitro. The release profile in vivo showed a high local concentration and low systemic exposure. The local INH concentration could be kept higher than its minimum inhibitory concentration over a period of 8 weeks, which proves that it is a promising strategy to improve the severe osteoarticular TB treatment.

We demonstrate a facile approach to constructing aggregation induced emission (AIE) fluorescent vesicles assembled using a PEG–POSS–(TPE)7 polymer. The narrow wall thickness provides an ideal confined space for creating fluorescence resonance energy transfer (FRET) systems between TPE donors and encapsulated FITC or DOX acceptors.

Here we demonstrate a simple and straightforward approach to prepare POSS-embedded hyperbranched (HB-POSS) polymers with customized molecular weights and sizes just by controlling the polymerization time. The polymers can be further used for building amphiphilic polymers, presenting morphological transition from micelle to vesicle in aqueous solution.

Here, we demonstrate the first known approach to create G1 and G2 POSS dendrimers with 9 and 65 POSS units, and 56 and 392 terminal vinyl groups from a 1 → 7 branching monomer in only one and three steps.

An ideal tissue engineering scaffold should imitate physical and biochemical cues of natural extracellular matrix and have interconnected porous structures with high porosity to provide adequate space for cell seeding, growth and proliferation, as well as nutrient delivery and metabolized product elimination. In this study, we examined the feasibility of fabricating microtubule-orientated poly(lactide-co-glycolide) (PLGA) scaffolds with interconnected pores (denoted as MOIP-PLGA) by an improved thermal-induced phase separation technique. We successfully constructed MOIP-PLGA using 1,4-dioxane as the first solvent and benzene or water with lower freezing point as the second solvent. Especially, when water was used, the MOIP-PLGA had higher porosity and it could guide rabbit aortic smooth muscle cells (SMCs) to better grow along the microtubule direction of the scaffold. Comparing with microtubule-orientated scaffold without interconnected pores (denoted as MONIP-PLGA), the proliferation and viability of SMCs cultured on MOIP-PLGA were higher. Moreover, basic fibroblast growth factor could be effectively bound on MOIP-PLGA by a plasma treatment technique and the growth factor could be slowly released in vitro, maintaining bioactivity.

An ideal vascular tissue engineering scaffold should imitate physical and biochemical cues in native vessels for guiding cell growth, differentiation and tissue formation. The tunica media provides a key structure and function support for native vessels. In this study, a film-like MNP-TGF/bFGF-PLGA scaffold that simulated physical and biochemical cues of tunica media in native vessels was fabricated by soft lithography combined with solution casting and phase separation technique. The scaffold had dual surface topographies of parallel arranged microgrooves and nanofiber structures, and interconnected pores to be able to deliver nutrient and eliminate metabolized products. The TGF-β1 and bFGF immobilized on the scaffold by silica nanoparticle binding and plasma treatment technique could maintain continuous release for 10 and 7 days, respectively. The synergy effect of the dual surface topography and released growth factors endowed the MNP-TGF/bFGF-PLGA scaffold with good capacity on regulating vascular smooth muscle cell (vSMC) phenotype. Importantly, the scaffold possessed good mechanical properties and could easily be rolled into a multilayer cylindrical tube as a promising biomimic vascular tissue engineering scaffold.

In recent years, hydroxyapatite (HAp) and β-tricalcium phosphate (TCP) were extensively used to prepare composite scaffolds for bone repair. However, due to a lack of systematical evaluation of HAp and TCP composite scaffolds for bone repair, their distinctions on bone regeneration in vivo have not been clearly clarified to date. In this study, we constructed HAp and TCP composite poly(lactic-co-glycolic acid) (PLGA) scaffolds with the same contents of HAp and TCP and similar structures and porosities, and systematically investigated their performance in the repair of rabbits’ calvarial bone defects. The HAp/PLGA scaffold possessed stronger mechanical property and higher cell proliferation than the TCP/PLGA scaffold, endowing it with better performance of bone regeneration at an early stage. Since TCP could greatly neutralize degraded acidic products and be slowly absorbed in vivo to release occupied room for new bone growth compared to HAp, the TCP/PLGA scaffold yielded more intact new bone for long-term repair of the defects. Our results clearly demonstrate that TCP is a superior bioceramic for bone tissue engineering, showing promise for the perfect repair of bone defects via tissue engineering.