Molecular switches: Highly efficient acido- and photoswitchable frequency doublers (see scheme) based on the indolinooxazolidine core are studied by means of hyper-Rayleigh experiments and quantum-chemical calculations.To optimize the nonlinear optical (NLO) contrast, a series of indolinooxazolidine derivatives with electron-withdrawing substituents in the para position on the indolinic residue have been synthesized. Their linear and nonlinear optical properties have been characterized by UV-visible absorption and hyper-Rayleigh scattering measurements, as well as by ab initio calculations. The two-way photo- or pH-triggered switching mechanism has been demonstrated by comparing the absorption spectra of the zwitterionic and protonated open forms (POF). Hyper-Rayleigh measurements have revealed that the second-order NLO contrast between the closed indolinooxazolidine and the open pi-conjugated colored forms remain very large upon substitution. Theory and measurements show that for the POFs the amplitude of the first hyperpolarizability follows the Hammett parameters of the withdrawing groups. However, because the measurements are performed in resonance, to recover this behavior, elaborate procedures including homogeneous and inhomogeneous broadenings, as well as single-mode vibronic structures are necessary to extrapolate to the static limit.

In this study, two different biomaterials were fabricated and their potential use as a bilayer scaffold for skin tissue engineering applications was assessed. The upper layer biomaterial was a Poly(ε-caprolactone-co-lactide)/Poloxamer (PLCL/Poloxamer) nanofiber membrane fabricated using electrospinning technology. The PLCL/Poloxamer nanofibers (PLCL/Poloxamer, 9/1) exhibited strong mechanical properties (stress/strain values of 9.37±0.38 MPa/187.43±10.66%) and good biocompatibility to support adipose-derived stem cells proliferation. The lower layer biomaterial was a hydrogel composed of 10% dextran and 20% gelatin without the addition of a chemical crosslinking agent. The 5/5 dextran/gelatin hydrogel displayed high swelling property, good compressive strength, capacity to present more than 3 weeks and was able to support cells proliferation. A bilayer scaffold was fabricated using these two materials by underlaying the nanofibers and casting hydrogel to mimic the structure and biological function of native skin tissue. The upper layer membrane provided mechanical support in the scaffold and the lower layer hydrogel provided adequate space to allow cells to proliferate and generate extracellular matrix. The biocompatibility of bilayer scaffold was preliminarily investigated to assess the potential cytotoxicity. The results show that cell viability had not been affected when cocultured with bilayer scaffold. As a consequence, the bilayer scaffold composed of PLCL/Poloxamer nanofibers and dextran/gelatin hydrogels is biocompatible and possesses its potentially high application prospect in the field of skin tissue engineering.

In the management of accelerating wound healing, moist environments play an important role. Compared with other scaffolds of various forms, hydrogels can maintain a moist environment in the wound area. They are cross-linked hydrophilic polymeric networks that resemble natural soft tissues and extracellular matrices. Among them, injectable hydrogels have attracted great attention in wound repair, as they can be injected into irregular-shaped skin defects and formed in situ to shape the contour of different dimensions. The excellent compliance makes hydrogels easy to adapt to the wound under different conditions of skin movement. Here, we oxidized hydroxyethyl starch (O-HES) and modified carboxymethyl chitosan (M-CMCS) to fabricate an in situ forming hydrogel with excellent self-recoverable extensibility−compressibility, biocompatibility, biodegradability, and transparency for accelerating wound healing. The oxidation degree of O-HES was 74%. The amino modification degree of M-CMCS was 63%. M-CMCS/O-HES hydrogels were formed through the Schiff base reaction. The physicochemical properties of M-CMCS/O-HES hydrogels with various ratios were investigated, and M-CMCS/O-HES hydrogel with a volume ratio of 5:5 exhibited appropriate gelation time, notable water-retaining capacity, self-recoverable conformal deformation, suitable biodegradability, and good biocompatibility for wound-healing application. Then, skin wound-healing experimental studies were carried out in Sprague−Dawley rats with fullthickness skin defects. Significant outcomes were achieved in the M-CMCS/O-HES hydrogel-treated group including higher wound closure percentage, more granulation tissue formation, faster epithelialization, and decreased collagen deposition. These findings demonstrate that using the obtained M-CMCS/O-HES hydrogels is a promising therapeutic strategy for wound healing.

Autoimmune deficiency and destruction in either βcell mass or function can cause insufficient insulin levels and, as a result, hyperglycemia and diabetes. Thus, promoting β-cell proliferation could be one approach toward diabetes intervention. In this report we describe the discovery of a potent and selective DYRK1A inhibitor GNF2133, which was identified through optimization of a 6-azaindole screening hit. In vitro, GNF2133 is able to proliferate both rodent and human β-cells. In vivo, GNF2133 demonstrated significant dose-dependent glucose disposal capacity and insulin secretion in response to glucosepotentiated arginine-induced insulin secretion (GPAIS) challenge in rat insulin promoter and diphtheria toxin A (RIP-DTA) mice. The work described here provides new avenues to disease altering therapeutic interventions in the treatment of type 1 diabetes (T1D).

Hydrogels play a very important role in cartilage tissue engineering. Here, we oxidized dextran (Odex) and modified gelatin (Mgel) to fabricate a fast forming hydrogel without the addition of a chemical crosslinking agent. The dynamic gelling process was measured through rheological measurements. The microstructure was examined by lyophilizing to get porous scaffolds. Biological assessment was performed through CCK-8 assays by using synovium-derived mesenchymal cells (SMSCs) at 1, 3, 7 and 14 days. In vivo evaluation for application in cartilage tissue engineering was performed 8 weeks after subcutaneous injection of SMSCloaded Odex/Mgel hydrogels combined with TGF-b3 in the dorsa of nude mice. According to the results, a fast forming hydrogel was obtained by simply modifying dextran and gelatin. Moreover, the Odex/Mgel hydrogel exhibited good biocompatibility in cultures of SMSCs and a homogeneous distribution of live cells was achieved inside the hydrogels. After 8 weeks, newly formed cartilage was achieved in the dorsa of nude mice; no inflammatory reaction was observed and high production of GAGs was shown. The method provides a strategy for the design and fabrication of fast in situ forming hydrogels. The Odex/ Mgel hydrogel could be used for the regeneration of cartilage in tissue engineering.

Hemostasis in orthopedic osteotomy or bone cutting requires different methods and materials. The bleeding of bone marrow can be mostly stopped by bone wax. However, the wax cannot be absorbed, which leads to artificial prosthesis loosening, foreign matter reaction, and infection. Here, a bioactive glass/chitosan/carboxymethyl cellulose (BG/CS/CMC) composite scaffold was designed to replace traditional wax. WST-1 assay indicated the BG/CS/CMC composite resulted in excellent biocompatibility with no cytotoxicity. In vivo osteogenesis assessment revealed that the BG/CS/CMC composite played a dominant role in bone regeneration and hemostasis. The BG/CS/CMC composite had the same hemostasis effect as bone wax; in addition its biodegradation also led to the functional reconstruction of bone defects. Thus, BG/CS/CMC scaffolds can serve as a potential material for bone repair and hemostasis in critical-sized bone defects.

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