AIEgen-Enabled Multicolor Visualization for the Formation of Supramolecular Polymer Networks.

Extensive reports on the use of supramolecular polymer networks (SPNs) in self-healing materials, controlled release system and degradable products have led more researchers to tap their potential owing to the unique properties. Yet, the attendant efforts in the visualization through conventional luminescence methods during the formation of SPNs have been met with limited success. Herein, we designed a special type of SPNs prepared by PPMU polymer chains containing pyrene benzohydrazonate (PBHZ) molecules as AIEgens for the multicolor visualization with naked eyes. The complete detection of the formation process of the networks relied on the PBHZ molecules with aggregation-induced ratiometric emission (AIRE) effect, which enabled the fluorescence of the polymer networks transits from blue to cyan, and then to green with the increasing crosslinking degree derived from the hydrogen bonds between 2-ureido-4-pyrimidone (UPy) units of the polymer chains. Additionally, we certificated the stimuli-responsiveness of the obtained SPNs, and the fluorescence change, as well as observing the morphology transition. The AIEgen-enabled multicolor visualization of the formation of SPNs may provide better understanding of the details of the crosslinking interactions in the microstructural evolution, giving more inspiration for the multifunctional products based on SPNs.

A Strategy Based on Aggregation-Induced Ratiometric Emission to Differentiate Molecular Weight of Supramolecular Polymers.

Molecular weight has an important bearing on the properties of supramolecular polymers. However, the intuitive differentiation of the molecular weight of supramolecular polymers remains challenging. Given this situation, establishing a reliable relationship between fluorescence properties and molecular weight may be a promising strategy. Herein, we prepared a supramolecular monomer M1 with aggregation-induced ratiometric emission characteristics. With the increasing M1 concentration (0.100-100 mM), the average degree of polymerization (DPDOSY ) rose from 1.00 to 293. Meanwhile, the color changed from dark blue to cyan, finally to yellow-green in the same concentration range. Hence, the intuitive relationship between DPDOSY and fluorescence colors was constructed, allowing the visual differentiation of molecular weight. Moreover, the fluorescence color could be regulated by introducing a competitive molecule to induce the depolymerization of supramolecular polymers.

Differential physical, rheological, and biological properties of rapid in situ gelable hydrogels composed of oxidized alginate and gelatin derived from marine or porcine sources.

Marine derived gelatin is not known to associate with any communicable diseases to mammals and could be a reasonable substitute for gelatin derived from either bovine or porcine sources. The low melting point of marine gelatin (8 degrees C) also offers greater formulation flexibility than mammalian derived gelatins. However, the sub-optimal physical properties of marine gelatin generally limit the interest to further develop it for biomedical applications. This study aimed at investigating the feasibility of using oxidized alginate (Oalg) as a high activity macromolecular crosslinker of marine gelatin to formulate in situ gelable hydrogels with the goal of enhancing the latter's physical properties. The performance of Oalg/marine gelatin hydrogel was compared to Oalg/porcine gelatin hydrogel; in general, the physicomechanical properties of both hydrogels were comparable, with the hydrogels containing porcine gelatin exhibiting moderately higher mechanical strengths with shorter gelation times, smaller size pores, and higher swelling ratios. On the contrary, the biological performances of the two hydrogels were significantly difference. Cells cultured in the marine gelatin derived hydrogel grew significantly faster, with greater than 60% more cells by 7 days and they exhibited more spread-out conformations as compared those cultured in the porcine derived hydrogel. Production of ECM by cells cultured in the Oalg/marine gelatin hydrogel was up to 2.4 times greater than that of in the Oalg/porcine gelatin hydrogel. The biodegradation rate of the hydrogel formulated from marine gelatin was greater than its counterpart prepared from porcine gelatin. These differences have important implications in the biomedical applications of the two hydrogels.

Porcine-derived xenogeneic bone/poly(glycolide-co-lactide-co-caprolactone) composite and its affinity with rat OCT-1 osteoblast-like cells.

Porcine-derived xenogeneic bone (PDXB) was derived from cancellous bone of adult porcine. Its morphology and structure were characterized by SEM, FTIR and XRD. A series of composite films consisting of PDXB and poly(glycolide-co-lactide-co-caprolactone) (PGLC) polymer were prepared. Because of the introduction of PGLC polymer, the PDXB/PGLC composites especially PDXB/PGLC(30/70) and PDXB/PGLC(50/50) showed good processability and mechanical properties. In addition, the hydrophilicity of the composites was enhanced as well since the PDXB component was hydrophilic. Osteoblast-like cells (OCT-1) were used as an in-vitro model to assess the affinity of the PDXB/PGLC composites. It was found that compared with the pure PGLC film, PDXB/PGLC(30/70) and PDXB/PGLC(50/50) composite films promoted cell attachment, proliferation and ALP (alkaline phosphatase) activity obviously. In addition, the cells preferred growing on the areas of exposed PDXB. It was considered that the hydrophilicity, osteoconductivity and appropriate surface roughness (Sa=3.30, 4.00 microm) induced by PDXB facilitate cell growth. However, the introduction of too much PDXB, such as PDXB/PGLC(70/30) film, would obtain an adverse effect on the cell growth since the value of Sa was up to 7.33 microm. It indicated that only the composites with appropriate surface topography could favor cell growth. Surface topography probably has a more important effect on cell growth process than surface chemistry.

Preparation and evaluation of poly(L-lactide-co-glycolide) (PLGA) microbubbles as a contrast agent for myocardial contrast echocardiography.

A kind of absorbable PLGA microbubble-based contrast agent (PLGA microspheres with porous or hollow inner structure) was fabricated by an improved double emulsion-solvent evaporation method. The contrast efficiency was evaluated and proved both in vitro and in vivo. By adjusting the polymer concentration and volume of the inner aqueous phase during the fabrication of microbubbles, the inner structure of the microbubbles could be controlled. Both air-filled and perfluoropropane-filled microbubbles can opacify the left ventricle. However, when compared with air-filled microbubbles, perfluoropropane-filled microbubbles can produce significantly longer enhancement in left ventricle in the dog model due to the lower diffusivity and lower solubility of perfluoropropane in blood. A suspension of perfluoropropane-filled PLGA microbubbles (1.8 microm average microbubbles size, 2 x 10(8) microbubbles/mL concentration) has successfully and safely achieved myocardial opacification in closed-chest dogs. A perfusion defect was observed in both of the two dogs with acute myocardial infarction with Power Contrast Imaging (PCI) triggered technology. In the examination of contrast in both ventricular and myocardial opacification, the high mechanical index (MI) was found to have superior contrast sensitivity over the low MI for PLGA-based contrast agents.

Delivery of rosiglitazone from an injectable triple interpenetrating network hydrogel composed of naturally derived materials.

An in situ gelable and biodegradable triple-interpenetrating network (3XN) hydrogel, completely devoid of potentially cytotoxic extraneous small molecule crosslinkers, is formulated from partially oxidized dextran (Odex), teleostean and N-carboxyethyl chitosan (CEC). Both the rheological profile and mechanical strength of the 3XN hydrogel approximate the combined characteristics of the three individual hydrogels composed of the binary partial formulations (i.e., Odex/CEC, Odex/teleostean, and CEC/teleostean). The 3XN hydrogel is considerably more resistant to fibroblast-mediated degradation compared to each partial formulation in cell culture models; this is attributable to the interpenetrating triple-network structure. The presence of teleostean in the 3XN hydrogel imparts cell affinity, constituting an environment amenable to fibroblast growth. in vivo subdermal injection into mouse model shows that the 3XN hydrogel does not induce extensive inflammatory response nor is there any evidence of tissue necrosis, further confirming the non-cytotoxicity of the hydrogel and its degradation byproducts. Importantly, the capability of the 3XN hydrogel to serve as a sustained drug delivery vehicle is confirmed using rosiglitazone as a model drug. The presence of rosiglitazone profoundly changes the cell/tissue interactions with the subdermally injected 3XN hydrogel. Rosiglitazone suppresses both the inflammatory response and tissue repair in a dose-dependent manner and considerably moderated the hydrogel degradation.

A rapid, in situ gelable hydrogel composed of teleostean and alginate.

A series of in situ gelable hydrogels has been prepared from oxidized alginate (Oalg) and teleostean. The gelation process is monitored rheologically; the effects of gelling temperature, oxidation degree of alginate and weight ratio of Oalg/teleostean on gelation are investigated. The results show that the Oalg/teleostean system solidifies quickly at body temperature. Moreover, the structure of the hydrogels is highly porous, the pore sizes, as well as swelling and degradation, can be controlled by varying the cross-linking density. Both gelation time and mechanical properties of the Oalg/teleostean system can be modulated by adjusting the oxidation degree of alginate and the weight ratio of Oalg/teleostean. The potential toxicity of the hydrogels are determined by long-term in vitro viability tests and the results reveal that the hydrogels formulations are non-cytotoxic; in parallel, the Oalg/teleostean hydrogel is amenable to cell attachment, proliferation and migration.

Multi-morphological biodegradable PLGE nanoparticles and their drug release behavior.

A series of amphiphilic tri-block copolymers based on poly(lactide-co-glycolide)-b-poly(ethylene oxide)-b-poly(lactide-co-glycolide) (PLGE) with various segment ratios of PEO/PLGA and segment lengths of PEO were synthesized. Multi-morphological biodegradable nanoparticles - PLGE-NPs were fabricated by an improved emulsion/solvent evaporation technique in the absence of surfactant. By adjusting segment ratio of PLGA/PEO (w/w) and molecular weight of PEO, various morphological and nanoscale sized spheres, elliptic spheres, short rods and threads could be formed. The auto-assembling mechanism of the PLGE-NPs and influencing effectors of composition of the PLGE on morphology of the PLGE-NPs were discussed. The PLGE-NPs were biodegradable, and the factors that affected the degradation rate of the PLGE-NPs were also discussed. By using the amphiphilic PLGE polymer, the biodegradable nanoscale immunosuppressive agent - multi-morphological Cyclosporine (CsA)-loaded PLGE-NPs was fabricated. CsA release behavior of the CsA-loaded PLGE-NPs in vitro was determined, and the effect factors on CsA release behavior of the CsA-loaded PLGE-NPs were discussed.