We present the first cell-attachable and visible-light-crosslinkable bioinks based on gelatin methacryloyl (GelMA) with eosin Y (EY) photoinitiation for stereolithography three-dimensional (3D) bioprinting. To develop a visible-light-crosslinkable hydrogel, we systematically studied five combinations of GelMA and EY photoinitiator with various concentrations. Their mechanical properties, microstructures, and cell viability and confluency after encapsulation were investigated rigorously to elucidate the effects of the EY and GelMA macromer concentrations on the characteristics of the hydrogel. Experimental results show that the compressive Young's modulus and pore size are positively affected by the concentration of EY, whereas the mass swelling ratio and cell viability are negatively affected. Increasing the concentration of GelMA helps in improving the compressive Young's modulus and cell attachment. We further employed the developed visible-light-based stereolithography bioprinting system to print the patterned cell-laden hydrogels to demonstrate the bioprinting applications of the developed hydrogel. We observed good cell proliferation and the formation of a 3D cellular network inside the printed pattern at day 5, which proves the great feasibility of using EY-GelMA as the bioinks for biofabrication and tissue engineering.

A direct laser bioprinting (DLBP) system is introduced in this work. The DLBP system applies visible-laser-induced photo-crosslinking at a wavelength of 405 nm using the photoinitiator VA-086. It is shown that such a system can fabricate vertical structures with fine features (less than 50 µm) and high cell viability (greater than 95%). Experimental characterizations and theoretical simulations are presented, and good agreement is seen between the experiments and theory. The DLBP system is applied to the fabrication of (1) cell-laden hydrogel microgrids, (2) hydrogel microwells, as well as a test of (3) cell encapsulation, and (4) cell seeding. The DLBP system is found to be a promising tool for bioprinting.

Divergent bicycle paths: A chemodivergent desymmetrization occurs after an initial enantioselective carbometalation step. The reaction brings a solution to the challenging problem of the enantioselective ring‐opening of diazabicyclo[2.2.1]heptanes to obtain arylated cyclopentenamines (see scheme, right). An alternative reaction pathway was discovered in which CH insertion/1,4‐metal migration occurs to give reductive arylation products (left).

Although ketone enamines are widely used in organic synthesis, aldehyde enamines are rarely employed due to the limitations of their preparation using known methods (need for acid or base, excess of amine, and/or elevated temperature). We have successfully developed rapid and particularly mild condensation conditions (1 h, 0 degrees C, 1.2 equiv of amine) leading to di- and trisubstituted enamines with excellent conversion (84-100%). Remarkably high chemoselectivity was observed with complete discrimination between aldehyde and ketone, among other functional groups positively tested.

[reaction: see text] Vilsmeier-Haack type cyclizations proved to be particularly efficient for generating parts of the polycyclic cores of many alkaloids, although only monocyclizations have so far been reported. With the goal of rapidly and efficiently constructing polycyclic alkaloids, we decided to exploit the Vilsmeier-Haack reaction by utilizing iminium ions successively generated and trapped with tethered nucleophiles. To develop such a strategy, we had to set the first cyclization. This constitutes a great challenge in itself because amide activation conditions are usually not compatible with tethered nucleophiles, except for indoles and aromatic rings which have already been reported. This paper describes the comprehensive study of intramolecular addition of silyl enol ethers, allylsilanes, and enamines to chemoselectively activated formamides, aliphatic amides, and lactams. Good to excellent yields were obtained for the 5-exo, 6-exo, and 6-endo modes of cyclization. Moreover, we demonstrated that the species in solution after the cyclization are iminium ions. This is highly encouraging for the development of bis-cyclization strategies. An expeditious total synthesis of (+/-)-tashiromine is also reported.

An enantio-, regio-, and diastereoselective rhodium(I)-catalyzed desymmetrization of a meso-cyclic allylic dicarbonate with organoboronic acid nucleophiles is described. The rhodium(I) catalyst formed in situ from [Rh(cod)OH]2 and Xyl-P-PHOS allowed the S(N)2' allylic substitution product to be obtained with a range of arylboronic acids in enantiomeric excesses of up to 92% with regioselectivities of up to >20:1.

Stereolithography-based bioprinting offers advantages in resolution and rapid printing time, and thus has received major attention in recent years. However, traditional stereolithography-based bioprinting utilizes an ultraviolet light which may cause mutagenesis and carcinogenesis of cells. In this paper, we present a new visible light crosslinkable bioink that is based on cell-adhesive gelatin. The bioink consists of Eosin Y (EY) based photoinitiator and gelatin methacrylate (GelMA) pre-polymer solution. We examined the feasibility of using visible light from a commercial beam projector to pattern the EY-GelMA bioink. We measured the absorbance of bioink to characterize its sensitivity to visible light and performed bioprinting to test its ability to promote cell adhesion. It is found that the EY-GelMA bioink has an absorption peak at roughly 522 nm, and that it can be successfully crosslinked by visible light from the commercial projector. We performed the bioprinting experiments and visualized the cell morphology using nuclei/F-actin staining. Experimental results show that most of the cells attached to the EY-GelMA bioink after five days' culturing. Ultimately, the EY-GelMA bioink can support both visible light crosslinking and cell adhesion, offering great potential in bioprinting and tissue engineering.

Hyaluronic acid is a native extra-cellular matrix derivative that promises unique properties, such as anti-inflammatory response and cell-signaling with tissue-specific applications under its bioactive properties. Here, we investigate the importance of the duration of synthesis to obtain photocrosslinkable methacrylated hyaluronic acid (MeHA) with high degree of substitution. MeHA with high degree of substitution can result in rapid photocrosslinking and can be used as a bioink for stereolithographic (SLA) three dimensional 3D bioprinting. Increased degree of substitution results Our findings show that a ten-day synthesis results in an 88% degree of methacrylation (DM), whereas three-day and five-day syntheses result in 32% and 42% DM, respectively. The rheological characterization revealed an increased rate of photopolymerization with increasing DM. Further, we developed a hybrid bioink to overcome the non-cell-adhesive nature of MeHA by combining it with gelatin methacryloyl (GelMA) to fabricate 3D cell-laden hydrogel scaffolds. The hybrid bioink exhibited a 55% enhancement in stiffness compared to MeHA only and enabled cell-adhesion while maintaining high cell viability. Investigations also revealed that the hybrid bioink was a more suitable candidate for stereolithography (SLA) 3D bioprinting than MeHA because of its mechanical strength, printability, and cell-adhesive nature. This research lays out a firm foundation for the development of a stable hybrid bioink with MeHA and GelMA for first-ever use with SLA 3D bioprinting.