Tissue engineered conduits have great promise for bridging peripheral nerve defects by providing physical guiding and biological cues. A flexible method for integrating support cells into a conduit with desired architectures is wanted. Here, a 3D-printing technology is adopted to prepare a bio-conduit with designer structures for peripheral nerve regeneration. This bio-conduit is consisted of a cryopolymerized gelatin methacryloyl (cryoGelMA) gel cellularized with adipose-derived stem cells (ASCs). By modeling using 3D-printed “lock and key” moulds, the cryoGelMA gel is structured into conduits with different geometries, such as the designed multichannel or bifurcating and the personalized structures. The cryoGelMA conduit is degradable and could be completely degraded in 2-4 months in vivo. The cryoGelMA scaffold supports the attachment, proliferation and survival of the seeded ASCs, and up-regulates the expression of their neurotrophic factors mRNA in vitro. After implanted in a rat model, the bio-conduit is capable of supporting the re-innervation across a 10 mm sciatic nerve gap, with results close to that of the autografts in terms of functional and histological assessments. The study describes an indirect 3D-printing technology for fabricating cellularized designer conduits for peripheral nerve regeneration, and could lead to the development of future nerve bio-conduits for clinical use.
It remains highly challenging to identify small molecule‐based photothermal agents with a high photothermal conversion efficiency (PTCE). Herein, we adopt a double bond‐based molecular motor concept to develop a new class of small photothermal agents to break the current design bottleneck. As the double‐bond is twisted by strong twisted intramolecular charge transfer (TICT) upon irradiation, the excited agents can deactivate non‐radiatively through the conical intersection (CI) of internal conversion, which is called photoinduced nonadiabatic decay. Such agents possess a high PTCE of 90.0 %, facilitating low‐temperature photothermal therapy in the presence of a heat shock protein 70 inhibitor. In addition, the behavior and mechanism of NIR laser‐triggered molecular motions for generating heat through the CI pathway have been further understood through theoretical and experimental evidence, providing a design principle for highly efficient photothermal and photoacoustic agents.
A robust platform is developed to assemble sub-10 nm organic aggregation-induced emission (AIE) particles using four different AIE luminogens (AIEgens) with emissions from green to the second near-infrared window (NIR-II). They are called AIE quantum dots (QDs) to distinguish from typical AIE dots which are larger than 25 nm. Compared with AIE dots that are larger than 25 nm, AIE QDs allow more efficient cellular uptake and imaging without surface modification of any membrane-penetrating peptides or other targeting molecules. NIR-II AIEgens, which have nearly no background fluorescence from organisms, are used to demonstrate that AIE QDs can achieve high contrast at the tumor as small as 80 mm 3 and evade the liver more efficiently than AIE dots. AIE QDs hold a good promise for sensitive and precise diagnosis of the latent solid tumor in clinical medicine with much lower offtargeting to the liver than AIE dots.
We report that carbonate esters could turn hydrophobic camptothecin (CPT)-unsaturated fatty acid prodrugs into nanoaggregates in aqueous solution. The active CPT could be rapidly released once triggered by a reductive stimulus when a carbonate ester was combined with a disulfide bond, resulting in a potent in vivo antitumor activity.
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