Mechanically tunable photo-cross-linkable bioinks for osteogenic differentiation of MSCs in 3D bioprinted constructs

3D bioprinting technique renders a plausible solution to tissue engineering applications, mainly bone tissue regeneration, which could provide the microenvironment with desired physical, chemical, and mechanical properties. However, the mechanical and structural stability of current natural polymers is a critical issue in the fabrication of bone tissue-engineered scaffolds. To overcome these issues, we have developed 3D bioprintable semi-synthetic polymers derived from natural (sodium alginate, A) and synthetic (polyethylene glycol, PEG) biopolymers. In order to enhance the cross-linking properties and biocompatibility, we have functionalized these polymers with acrylate and methacrylate chemical moieties. These selected combination of natural and synthetic polymers improved the mechanical strength due to the synergistic effect of covalent as well as ionic bond formation in the hydrogel system, which is evident from the tested tensile data. Further, the feasibility of 3D bioprinting of acrylate and methacrylate functionalized PEG and hydrogels have been tested for the biocompatibility of the fabricated structures with human umbilical cord mesenchymal stem cells (UMSCs). Further, these bioprinted scaffolds were investigated for osteogenic differentiation of UMSCs in two types of culture conditions: namely, i) with osteoinduction media (with OIM), ii) without osteoinduction media (w/o OIM). We have examined the osteoinductivity of scaffolds with the activity of alkaline phosphatase (ALP) content, and significant changes in the ALP activity was observed with the stiffness of developed materials. The extent osteogenic differentiation was observed by alizarin red staining and reverse transcription PCR analysis. Elevated levels of ALP, RUNX2 and COL1 gene expression has been observed in without OIM samples on week 1 and week 3. Further, our study showed that the synthesized alginate methacrylate (AMA) without osteoinduction supplement with young's modulus of 0.34 MPa has a significant difference in ALP quantity and gene expression over the other reported literature. Thus, this work plays a pivotal role in the development of 3D bioprintable and photo-cross-linkable hydrogels in osteogenic differentiation of mesenchymal stem cells. © 2021 Elsevier B.V

[2 + 2 + 2] Cyclotrimerization with Propargyl Halides as Copartners: Formal Total Synthesis of the Antitumor Hsp90 Inhibitor AT13387

Heat shock protein 90 (Hsp90) inhibitors play a remarkable role in cellular growth, and they were shown to exhibit antitumor activity. The Hsp90 inhibitor AT13387 (onalespib) is under clinical trials for the treatment of refractory gastrointestinal stromal tumors. Recently, it was demonstrated that this compound also exhibits inhibition against bladder cancer. Here, we report isoindoline- and isoindolinone-based (halomethyl)­benzenes via a [2 + 2 + 2] cyclotrimerization in the presence of catalytic amounts of Mo­(CO)₆. This strategy has been extended to synthesize the key precursor of the Hsp90 inhibitor, AT13387

Hexacyclo[7.5.1.01,6.06,13.08,12.010,14]pentadecane-7,15-dione

The structure of the title cage compound, C15H16O2, comprises eight fused rings, viz. one four-membered, four five-membered and three six-membered. One of the internal C—C bonds is unusually long for a cyclobutane bond length [1.607 (3) Å] and is comparable with the equivalent value of 1.598 (4) Å in the unsaturated homolog hexacyclo[7.4.2.01,9.03,7.04,14.06,15]pentadeca-10,12-diene-2,8-dione

Two directional approach to spirocycles containing bicyclo[2.2.2]octane system <em>via</em> a [2+2+2] co-trimerization and Diels-Alder reaction

1231-1236A simple and atom economic/step economic route for the synthesis of bis-armed spirocycles including bis-armed spirosulfone derivative containing bicyclo[2.2.2]octane ring system by utilizing a MW assisted Mo(CO)6 catalyzed two-directional [2+2+2] co-trimerization and the [4+2] cycloaddition reaction as key steps, is reported