Identification of VISTA regulators in macrophages mediating cancer cell survival.

Numerous human cancers have exhibited the ability to elude immune checkpoint blockade (ICB) therapies. This type of resistance can be mediated by immune-suppressive macrophages that limit antitumor immunity in the tumor microenvironment (TME). Here, we elucidate a strategy to shift macrophages into a proinflammatory state that down-regulates V domain immunoglobulin suppressor of T cell activation (VISTA) via inhibiting AhR and IRAK1.

Multifunctional Dopamine-Based Hydrogel Microneedle Electrode for Continuous Ketone Sensing.

Diabetic ketoacidosis (DKA), a severe complication of type 1 diabetes (T1D), is triggered by production of large quantities of ketone bodies, requiring patients with T1D to constantly monitor their ketone levels. Here, a skin-compatible hydrogel microneedle (HMN)-continuous ketone monitoring (HMN-CKM) device is reported. The sensing mechanism relies on the catechol-quinone chemistry inherent to the dopamine (DA) molecules that are covalently linked to the polymer structure of the HMN patch.

"Smart" Matrix Microneedle Patch Made of Self-Crosslinkable and Multifunctional Polymers for Delivering Insulin On-Demand.

A transdermal patch that delivers insulin at high glucose concentrations can offer tremendous advantages to ease the concern of safety and improve the quality of life for people with diabetes. Herein, a novel self-crosslinkable and glucose-responsive polymer-based microneedle patch (MN) is designed to deliver insulin at hyperglycemia. The microneedle patch is made of hyaluronic acid polymers functionalized with dopamine and 4-amino-3-fluorophenylboronic acid (AFBA) that can be quickly crosslinked upon mixing of the polymer solutions in the absence of any chemicalcrosslinking agents or organic solvents.

A Conductive Hydrogel Microneedle-Based Assay Integrating PEDOT:PSS and Ag-Pt Nanoparticles for Real-Time, Enzyme-Less, and Electrochemical Sensing of Glucose.

Continuous glucose meters (CGMs) have tremendously boosted diabetes care by emancipating millions of diabetic patients' need for repeated self-testing by pricking their fingers every few hours. However, CGMs still suffer from major deficiencies regarding accuracy, precision, and stability. This is mainly due to their dependency on an enzymatic detection mechanism.

A Conductive Hydrogel-Based Microneedle Platform for Real-Time pH Measurement in Live Animals.

Conventional microneedles (MNs) have been extensively reported and applied toward a variety of biosensing and drug delivery applications. Hydrogel forming MNs with the added ability to electrically track health conditions in real-time is an area yet to be explored. The first conductive hydrogel microneedle (HMN) electrode that is capable of on-needle pH detection with no postprocessing required is presented here.

Hydrogel Microneedle-Assisted Assay Integrating Aptamer Probes and Fluorescence Detection for Reagentless Biomarker Quantification.

Analyzing interstitial fluid (ISF) via microneedle (MN) devices enables patient health monitoring in a minimally invasive manner and in point-of-care settings. However, most MN-based diagnostic approaches require complicated fabrication processes and postprocessing of the extracted ISF or are limited to detection of electrochemically active biomarkers. Here, we show on-needle measurement of target analytes by integrating hydrogel microneedles with aptamer probes as the recognition elements.

"Smart" Composite Microneedle Patch Stabilizes Glucagon and Prevents Nocturnal Hypoglycemia: Experimental Studies and Molecular Dynamics Simulation.

Hypoglycemia is a major complication associated with insulin therapy in people with diabetes that could cause life-threatening conditions if untreated. Glucagon, a counter-acting hormone, is thus administered for rescue of severe hypoglycemia. However, due to the instability of glucagon, only limited medications are available for emergency use, which are unsuitable for patients with hypoglycemia unawareness or with the inability to self-administer, especially during sleep (namely, nocturnal hypoglycemia).

Covalent Antiviral Agents.

Nowadays, many viral infections have emerged and are taking a huge toll on human lives globally. Meanwhile, viral resistance to current drugs has drastically increased. Hence, there is a pressing need to design potent broad-spectrum antiviral agents to treat a variety of viral infections and overcome viral resistance.

Highlights on Advancing Frontiers in Tissue Engineering.

The field of tissue engineering continues to advance, sometimes in exponential leaps forward, but also sometimes at a rate that does not fulfill the promise that the field imagined a few decades ago. This review is in part a catalog of success in an effort to inform the process of innovation. Tissue engineering has recruited new technologies and developed new methods for engineering tissue constructs that can be used to mitigate or model disease states for study.

Transdermal delivery of a somatostatin receptor type 2 antagonist using microneedle patch technology for hypoglycemia prevention.

Hypoglycemia is a serious and potentially fatal complication experienced by people with insulin-dependent diabetes. The complication is usually caused by insulin overdose, skipping meals, and/or excessive physical activities. In type 1 diabetes (T1D), on top of impaired pancreatic α-cells, excessive levels of somatostatin from δ-cells further inhibit glucagon secretion to counteract overdosed insulin.

Crosslinking Strategies for 3D Bioprinting of Polymeric Hydrogels.

Three-dimensional (3D) bioprinting has recently advanced as an important tool to produce viable constructs that can be used for regenerative purposes or as tissue models. To develop biomimetic and sustainable 3D constructs, several important processing aspects need to be considered, among which crosslinking is most important for achieving desirable biomechanical stability of printed structures, which is reflected in subsequent behavior and use of these constructs. In this work, crosslinking methods used in 3D bioprinting studies are reviewed, parameters that affect bioink chemistry are discussed, and the potential toward improving crosslinking outcomes and construct performance is highlighted.

Glucose-Responsive Composite Microneedle Patch for Hypoglycemia-Triggered Delivery of Native Glucagon.

Insulin-dependent patients with diabetes mellitus require multiple daily injections of exogenous insulin to combat hyperglycemia. However, administration of excess insulin can lead to hypoglycemia, a life-threatening condition characterized by abnormally low blood glucose levels (BGLs). To prevent hypoglycemia associated with intensive insulin therapy, a "smart" composite microneedle (cMN) patch is developed, which releases native glucagon at low glucose levels.

Glucose regulation by modified boronic acid-sulfobetaine zwitterionic nanogels - a non-hormonal strategy for the potential treatment of hyperglycemia.

We have introduced a non-hormonal hyperglycemia treatment strategy by using an injectable glucose-responsive boronic acid- zwitterionic nanogel. The synthesized system, similar to an artificial liver, is capable of storing/releasing glucose at high/low blood glucose concentrations. In vivo performance revealed that the injection of the nanogels can effectively regulate blood glucose in type 1 diabetic rats for at least 6 hours.

Strategic design of a Mussel-inspired in situ reduced Ag/Au-Nanoparticle Coated Magnesium Alloy for enhanced viability, antibacterial property and decelerated corrosion rates for degradable implant Applications.

Magnesium (Mg) and its alloys have attracted much attention as a promising candidate for degradable implant applications however the rapid corrosion of magnesium inside the human body greatly limits its use as an implant material. Therefore, coating the alloy surface with a multifunctional film is a promising way to overcome the drawbacks. Here we propose for the first time a multifunction layer coating to enhance the cell viability, antibacterial property and decelerated corrosion rates to act as a novel material to be used for degradable implant Applications.

Effect of a functional polymer on the rheology and microstructure of sodium alginate.

Here, we report on the effect of functional copolymer poly(N-isopropylacrylamide-co-4-vinyl-phenylboronic acid) (NIBA) on the rheology and network structure formed by sodium alginate (SA) through linear and nonlinear viscoelasticity measurements. The hydrogel moduli at pH 3 increased with increasing NIBA addition, while the yield point decreased. Furthermore, these hydrogels showed strain-softening behavior, weak G″-overshoot marking the onset of nonlinearity, and good self-healing properties after large deformation.

Strategic Design and Fabrication of Biomimetic 3D Scaffolds: Unique Architectures of Extracellular Matrices for Enhanced Adipogenesis and Soft Tissue Reconstruction.

The higher rate of soft tissue impairment due to lumpectomy or other trauma greatly requires the restoration of the irreversibly lost subcutaneous adipose tissues. The nanofibers fabricated by conventional electrospinning provide only a superficial porous structure due to its sheet like 2D structure and thereby hinder the cell infiltration and differentiation throughout the scaffolds. Thus we developed a novel electrospun 3D membrane using the zwitterionic poly (carboxybetaine-co-methyl methacrylate) co-polymer (CMMA) through electrostatic repulsion based electrospinning for soft tissue engineering.

A mussel inspired self-expandable tubular hydrogel with shape memory under NIR for potential biomedical applications.

We engineered a novel shape memory polymer (SMP), a nanocomposite hydrogel containing polydopamine nanospheres (PDNs) as a self-expandable tubular hydrogel under near-infrared (NIR) irradiation. When NIR is applied to the nanocomposite hydrogel, the PDN nanoparticles absorb light, which is locally dissipated as heat to become the driving force for shape transition behavior. Since the fabricated PDN material has good mechanical properties, including rapid self-expandability and good biocompatibility, when developed with good heating properties under (NIR) irradiation, it might be useful for many biomedical applications such as the treatment of coronary artery disease.

On-demand drug release and hyperthermia therapy applications of thermoresponsive poly-(NIPAAm-co-HMAAm)/polyurethane core-shell nanofiber mat on non-vascular nitinol stents.

A functional cover made up of core-shell nanofibers with a unique combination of thermoresponsive polymeric shell and stretchable polymeric core for non-vascular nitinol stents that uses an alternating magnetic field (AMF) to induce heat in the stent for hyperthermia therapy and simultaneously release 5-fluorouracil and/or paclitaxel was designed. Varying the ratios of NIPAAm to HMAAm monomer resulted in different LCST properties for the synthesized copolymer and further utilized for an on-demand drug release. Biocompatibility test using NIH-3T3 fibroblast cells indicates that the composite with drug content is biocompatible and the in-vitro cancer cytotoxicity test using ESO26 and OE21 cancer cells proved that the material shows cancer cytotoxic properties via combination of dual drug and hyperthermia therapy.

pH/NIR Light-Controlled Multidrug Release via a Mussel-Inspired Nanocomposite Hydrogel for Chemo-Photothermal Cancer Therapy.

This study reports on an intelligent composite hydrogel with both pH-dependent drug release in a cancer environment and heat generation based on NIR laser exposure, for the combined application of photothermal therapy (PTT) and multidrug chemotherapy. For the first time in the literature, Dopamine nanoparticle (DP) was incorporated as a highly effective photothermal agent as well as anticancer drug, bortezomib (BTZ) carrier inside a stimuli responsive pNIPAAm-co-pAAm hydrogel. When light is applied to the composite hydrogel, DP nanoparticle absorbs the light, which is dissipated locally as heat to impact cancer cells via hyperthermia.

In Situ Synthesis of Antimicrobial Silver Nanoparticles within Antifouling Zwitterionic Hydrogels by Catecholic Redox Chemistry for Wound Healing Application.

A multifunctional hydrogel that combines the dual functionality of both antifouling and antimicrobial capacities holds great potential for many bioapplications. Many approaches and different materials have been employed to synthesize such a material. However, a systematic study, including in vitro and in vivo evaluation, on such a material as wound dressings is highly scarce at present.

A smart magnetic nanoplatform for synergistic anticancer therapy: manoeuvring mussel-inspired functional magnetic nanoparticles for pH responsive anticancer drug delivery and hyperthermia.

We report the versatile design of a smart nanoplatform for thermo-chemotherapy treatment of cancer. For the first time in the literature, our design takes advantage of the outstanding properties of mussel-inspired multiple catecholic groups - presenting a unique copolymer poly(2-hydroxyethyl methacrylate-co-dopamine methacrylamide) p(HEMA-co-DMA) to surface functionalize the superparamagnetic iron oxide nanoparticles as well as to conjugate borate containing anticancer drug bortezomib (BTZ) in a pH-dependent manner for the synergistic anticancer treatment. The unique multiple anchoring groups can be used to substantially improve the affinity of the ligands to the surfaces of the nanoparticles to form ultrastable iron oxide nanoparticles with control over their hydrodynamic diameter and interfacial chemistry.

Mussel-Inspired Electrospun Nanofibers Functionalized with Size-Controlled Silver Nanoparticles for Wound Dressing Application.

Electrospun nanofibers that contain silver nanoparticles (AgNPs) have a strong antibacterial activity that is beneficial to wound healing. However, most of the literature available on the bactericidal effects of this material is based on the use of AgNPs with uncontrolled size, shape, surface properties, and degree of aggregation. In this study, we report the first versatile synthesis of novel catechol moieties presenting electrospun nanofibers functionalized with AgNPs through catechol redox chemistry.

Hydrogen bonding in aprotic solvents, a new strategy for gelation of bioinspired catecholic copolymers with N-isopropylamide.

Copolymers of N-isopropylacrylamide (NIPAM) and dopamine methacrylate can establish a reversible, self-healing 3D network in aprotic solvents based on hydrogen bonding. The reactivity and hydrogen bonding formation of catechol groups in copolymer chains are studied by UV-vis and (1) H NMR spectroscopy, while reversibility from sol to gel and inverse as well as self-healing properties are tested rheologically. The produced reversible organogel can self-encapsulate physically interacting or chemically bonded solutes such as drugs due to thermosensitivity of the used copolymer.

Oscillations in modulus in solutions of graphene oxide and reduced graphene oxide with grafted poly-N-isopropylamide.

In a material consisting of graphene oxide or reduced graphene oxide and poly-N-isopropylamide (PNIPAM) in an aqueous solution, a new type of rheological behaviour is found. When subjecting the material to a short and relatively small deformation pulse, the modulus, which is observed by small deformations in the linear-viscoelastic or very slightly nonlinear range, oscillates with periodicities between 100 and several 1000 seconds; however, in many cases, it also increases systematically. The periodicity depends on the filler content and the sample preparation method (in situ polymerisation vs.

Graphene oxide/carbon nanotube composite hydrogels-versatile materials for microbial fuel cell applications.

Carbonaceous nanocomposite hydrogels are prepared with an aid of a suspension polymerization method and are used as anodes in microbial fuel cells (MFCs). (Poly N-Isopropylacrylamide) (PNIPAM) hydrogels filled with electrically conductive carbonaceous nanomaterials exhibit significantly higher MFC efficiencies than the unfilled hydrogel. The observed morphological images clearly show the homogeneous dispersion of carbon nanotubes (CNTs) and graphene oxide (GO) in the PNIPAM matrix.