3D printing of recombinant collagen/chitosan methacrylate/nanoclay hydrogels loaded with Kartogenin nanoparticles for cartilage regeneration.

Cartilage defects are frequently caused by trauma, illness and degradation of the cartilage. If these defects are not sufficiently treated, the joints will degrade irreversibly, possibly resulting in disability. Articular cartilage lacks blood vessels and nerves and is unable to regenerate itself, so the repair of cartilage defects is extremely challenging in clinical treatment. Tissue engineering technology is an emerging technology in cartilage repair and cartilage regeneration. 3D-printed hydrogels show great potential in cartilage tissue engineering for the fabrication of 3D cell culture scaffolds to mimic extracellular matrix. In this study, we construct a 3D-printed hydrogel loaded with nanoparticles by electrostatic interaction and photo cross-linking for the regeneration of cartilage, which has adaptable and drug-continuous release behavior. A photopolymerizable bioink was prepared using recombinant collagen, chitosan, nanoclay Laponite-XLG and nanoparticles loaded with Kartogenin (KGN). This bioink was added with KGN, a small molecule drug that promotes cartilage differentiation, and as a result, the 3D-printed CF/CM/3%LAP/KGN scaffolds obtained by extrusion printing is expected to be used for cartilage repair. It was shown that the 3D-printed scaffolds had good cytocompatibility for human bone marrow mesenchymal stem cells (hBMSCs) and exhibited excellent antimicrobial properties, the continuous release of KGN in the scaffold induced the hBMSCs differentiation into chondrocytes, which significantly enhanced the expression of collagen II and glycosaminoglycan. In vivo studies have shown that implantation of KGN-loaded scaffolds into cartilage-injured tissues promoted cartilage tissue regeneration. This study demonstrated that 3D-printed CF/CM/3%LAP/KGN scaffolds can be used for cartilage repair, which is expected to lead to new healing opportunities for cartilage injury-based diseases.

NASC 2023: Showcasing Diversity in North American Supramolecular Chemistry.

Diversity in supramolecular chemistry can showcase itself in many ways. This includes the diversity of thought and topics covered in research (from fundamental science to applications in biology and materials), as well as the diversity of people (e.g., diversity in race, gender, sexual orientation, country of origin, type of higher education institute, career stage,…). At the North American Supramolecular Chemistry (NASC) meetings, we aim to bring together the best that supramolecular chemistry has to offer in North America, create a sense of community and provide a platform for researchers at any stage of their career to present their work. NASC 2023 was the successful second edition of the NASC meeting series, and this proceedings article highlights the research and impressions of some of the speakers at NASC 2023.

A High-Affinity "Synthavidin" Receptor for Squaraine Dyes.

Strong-binding host-guest pairings in aqueous media have potential as "supramolecular glues" in biomedical techniques, complementing the widely-used (strept)avidin-biotin combination. We have previously found that squaraine dyes are bound very strongly by tetralactam macrocycles possessing anthracenyl units as cavity walls. Here we show that replacing the anthracenes with pentacyclic 5,7,12,14-tetrahydro-5,7,12,14-tetraoxapentacene (TOP) units generates receptors which bind squaraines with increased affinities (around Ka =1010  m-1 ) and improved selectivities. Binding can be followed through changes to squaraine fluorescence and absorbance. The TOP units are easy to prepare and potentially variable, while the TOP-based receptor shows improved photostability, both in itself and in complex with squaraines. The results suggest that this system could prove valuable in the further development of practical "synthavidin" chemistry.

Mixed Ligand Passivation as the Origin of Near-Unity Emission Quantum Yields in CsPbBr3 Nanocrystals.

Key features of syntheses, involving the quaternary ammonium passivation of CsPbBr3 nanocrystals (NCs), include stable, reproducible, and large (often near-unity) emission quantum yields (QYs). The archetypical example involves didodecyl dimethyl ammonium (DDDMA+)-passivated CsPbBr3 NCs where robust QYs stem from interactions between DDDMA+ and NC surfaces. Despite widespread adoption of this synthesis, specific ligand-NC surface interactions responsible for large DDDMA+-passivated NC QYs have not been fully established. Multidimensional nuclear magnetic resonance experiments now reveal a new DDDMA+-NC surface interaction, beyond established "tightly bound" DDDMA+ interactions, which strongly affects observed emission QYs. Depending upon the existence of this new DDDMA+ coordination, NC QYs vary broadly between 60 and 85%. More importantly, these measurements reveal surface passivation through unexpected didodecyl ammonium (DDA+) that works in concert with DDDMA+ to produce near-unity (i.e., >90%) QYs.

Supramolecular capture of highly polar amidosquaraine dye in water with nanomolar affinity and large turn-on fluorescence.

A supramolecular dye-capture system comprising anionic amidosquaraine guest and macrocyclic tetralactam host exhibits nanomolar affinity and "turn on" visible fluorescence. Utility is demonstrated with a new fluorescent assay for liposome leakage induced by the biomedically important enzyme phospholipase A2.

Tuning the allosteric sequestration of anticancer drugs for developing cooperative nano-antidotes.

A dual-cavity basket 16-, holding six γ-aminobutyric acids at its termini, encapsulates variously sized aromatics 2-7+, including four anthracyclines (8+-11+), driven by the hydrophobic effect and hydrogen bonding (HB). In particular, the formation of stable (K = 1012 M-2) anthracycline complexes [(8+-11+)2⊂16-], assembled into nanoparticles, occurred with positive homotropic cooperativity (α = 4K2/K1 = 1.1 ± 0.3 × 102-1.3 ± 0.7 × 103) in PBS medium. Importantly, weakening the first binding event (K1, i.e. by removing HBs) turned the second one (K2) more favorable. The finding is of interest for developing cooperative nano-antidotes acting as biodetoxifying agents.

Acetal-Functionalized Pillar[5]arene: A pH-Responsive and Versatile Nanomaterial for the Delivery of Chemotherapeutic Agents.

Acetal-functionalized pillar[5]arene (Ac-PA[5]) was prepared as a pH-responsive biomaterial. This biomaterial could be fabricated into nanoparticles with a narrow size distribution by an emulsion protocol. PA[5]-based nanoparticles were used to deliver anti-tumor drugs (paclitaxel and doxorubicin) in vitro. PA[5]-based nanoparticles were discovered to be a versatile drug delivery system (DDS) to incorporate a fluorescent dye (fluorescein) or a targeting group (folic acid) via host-guest interactions. The resulting DDS could be used for the purpose of bioimaging or targeted delivery. Acetal-functionalization renders the system acid-labile to release encapsulated cargo during cell internalization, which is confirmed by confocal laser scanning microscopy (CLSM). A folic-acid-modified DDS shows a 5.1-fold enhancement in bioactivity in vitro due to the targeting effect. This DDS is a platform to conveniently integrate multiple functions.

Water-Soluble Pillar[n]arene Mediated Supramolecular Self-Assembly: Multi-Dimensional Morphology Controlled by Host Size.

We report tunable supramolecular self-assemblies formed by water-soluble pillar[n]arenes (WPns, n=5-7) and bipyridinium-azobenzene guests. Nanoscale or microscale morphology of self-assemblies in water was controlled by the host size of WPn. Supramolecular self-assemblies could undergo morphology conversion under irradiation with UV light.

Pro-guest and acyclic cucurbit[n]uril conjugated polymers for the controlled release of anti-tumor drugs.

We report "pro-guest" and acyclic cucurbit[n]uril conjugated polymers as supramolecular drug delivery systems (DDSs). These supramolecular DDSs could encapsulate anti-tumor drugs. Under acidic conditions, an acid-labile "pro-guest" degraded to become a "competing guest", which displaced and released the encapsulated drug at a tunable rate.

Cholecystokinin octapeptide inhibits the inflammatory response and improves neurological outcome in a porcine model of cardiopulmonary resuscitation.

Previous studies have demonstrated that cholecystokinin octapeptide (CCK8) induces hypothermia and inhibits the systemic inflammatory response in septic shock in rat and murine models. The present study aimed to ascertain whether CCK8 induced hypothermia and improved the neurological outcomes in a porcine model of cardiopulmonary resuscitation (CPR). Ventricular fibrillation was induced and left untreated for 10 min in 12 male Bama miniature pigs. Defibrillation was attempted after 5 min of CPR. At 5 min following resuscitation, the pigs were randomized and equally assigned into the CCK8 or the control group. CCK8 was continuously infused for 1 h at a dose of 44.4 µg/kg/h and a rate of 20 ml/h in the CCK8 group. Body temperature, hemodynamic measurements and post-resuscitation myocardial function were monitored in the first 4 h following CPR. Neuron specific enzyme (NSE), S100B protein, tumor necrosis factor (TNF)-α and interleukin (IL)-6 were measured at baseline and 4, 12 and 24 h following resuscitation. The neurological deficient score (NDS) was recorded and cerebral samples were collected for terminal deoxynucleotidyl-transferase-mediated dUTP nick end labelling assay and integrated optical density (IOD) analysis at 24 h following CPR. The results revealed that hypothermia was not induced by CCK8; however, post-resuscitation NSE, S100B, IL-6 and TNF-α were significantly decreased, and NDS and IOD were significantly improved in the CCK8 group compared with the control group (P<0.05). The present study revealed that in a porcine model of CPR, CCK8 does not induce hypothermia, but inhibits the inflammatory response and significantly improves neurological outcomes.