Journal of Materials Chemistry B最新文献

The inability of articular cartilage to self-repair following injuries frequently precipitates osteoarthritis, profoundly affecting patients' quality of life. Given the limitations inherent in current clinical interventions, an urgent need exists for more effective cartilage regeneration methodologies. Previous studies have underscored the potential of electrical stimulation in cartilage repair, thus motivating the investigation of innovative strategies. The present study introduces a three-dimensional scaffold fabricated through a composite technique that leverages the synergy between piezoelectricity and biofactors to enhance cartilage repair. This scaffold is composed of polylactic acid (PLLA) and barium titanate (BT) for piezoelectric stimulation and at the bottom with a collagen-coated layer infused with fibroblast growth factor-18 (FGF-18) for biofactor delivery. Designed to emulate the properties of natural cartilage, the scaffold enables controlled generation of piezoelectric charges and the sustained release of biofactors. In vitro tests confirm that the scaffold promotes chondrocyte proliferation, matrix hyperplasia, cellular migration, and the expression of genes associated with cartilage formation. Moreover, in vivo studies on rabbits have illustrated its efficacy in catalyzing the in situ regeneration of articular cartilage defects and remodeling the extracellular matrix. This innovative approach offers significant potential for enhancing cartilage repair and holds profound implications for regenerative medicine.

Capturing circulating tumor cells (CTCs) from the peripheral blood of cancer patients, where they are disseminated among billions of other blood cells, is one of the most daunting challenge. We report OncoDiscover®, a multicomponent nano-system consisting of iron oxide (Fe₃O₄) nanoparticles (NPs), polyamidoamine generation 4 dendrimers (PAMAM-G4-NH₂), graphene oxide (GO) sheets and an anti-epithelial cell adhesion molecule (anti-EpCAM) antibody (Fe-GSH-PAMAM-GO-EpCAM) for the selective and precise capture of CTCs. We further evaluated this system for therapeutically important oncotargets, exemplifying overexpression of the programmed death ligand 1 (PD-L1) as a functional assay on CTCs in cancer patients. We retrospectively evaluated 134 cancer patients for the presence of CTCs and 113 (84%) showed the presence of CTCs. About 62 (55%) of the CTC +ve patients showed CTCs with PD-L1 expression. The personalized cancer detection demonstrated by the OncoDiscover® CTC analysis tool is highly relevant for cancer monitoring and treatment outcomes.

Hydrogels are three-dimensional, highly tunable material systems that can match the properties of extracellular matrices. In addition to being widely used to grow and modulate cell behavior, hydrogels can be made conductive to further modulate electrically active cells, such as neurons, and even incorporated into multielectrode arrays to interface with tissues. To enable conductive hydrogels, graphene flakes can be mechanically suspended into a hydrogel precursor. The conductivity of the hydrogel can be increased by increasing the weight percentage of graphene flakes in the precursor while maintaining the mechanical properties of the formed gel similar to the properties of neural tissue. By using a photocrosslinkable hydrogel matrix, such as gelatin methacrylate, with a photoabsorber, the conductive precursor solutions can be crosslinked into predefined complex patterns. Finally, the formulations can be used to support the growth of sensory neurons, derived from human induced pluripotent stem cells, for more than 7 weeks while the neurons remain viable. These scaffolds can be patterned into components of multielectrode arrays, to enable ultrasoft electrodes with tissue-matched properties for further interactions, both in vitro and in vivo, with the nervous systems.

The engineered phage YSY184, mimicking the extracellular matrix nanofiber, effectively promotes stem cell differentiation and angiogenesis. This study evaluated its safety in a mouse model, monitoring weight, immunogenicity, spleen immune responses, and macrophage infiltration. Rapid clearance of YSY184 was observed, with peak tissue presence within three hours, significantly reduced by 24 hours, and negligible after one month. No adverse physiological or pathological effects were detected post-administration, affirming YSY184's safety and underscore its potential for therapeutic use, warranting further clinical exploration.

Self-assembled small peptide-based nanoparticles (NPs) constitute a major section of the biomimetic smart NPs owing to their excellent compatibility and minimal adverse effects in the biological system. Here, we have designed a modified L-carnosine dipeptide analog, “Fmoc-β-Ala-L-His-(Trt)-o-methyl formate”, which was assembled along with a modified single amino acid, Fmoc-Arg-(Pbf)-OH and zinc ions to form stable and mono-dispersed L-carnosine analog NPs (CaNPs) with inherent anti-cancer properties. Furthermore, the CaNPs demonstrated an average size of ∼200 nm, making them suitable to invade the tumor site by following the enhanced permeability and retention (EPR) effect. Our studies depicted a remarkable cancer cell killing ability of the NPs of ∼82% in C6 glioma cells. Thereafter, cellular investigations were performed in C6 cells to analyze the influence of the NPs on cellular cytoskeleton integrity by using a phalloidin assay and anti-cancer efficacy by using calcein AM/PI, and an apoptosis assay further indicated their anti-cancer effect. Additionally, the NPs negatively impacted the ability of C6 cells to migrate across a premade scratch (∼44% wound closure) demonstrating their tendency to halt cancer cell migration and metastasis. Also, our NPs depicted ∼19.51 ± 0.17% permeability across the bEnd.3 transwell model establishing their BBB penetrability. Collectively, our results could positively implicate the successful anti-cancer potential of the minimalistic, biologically compliant, L-carnosine analog (Ca)-based nanostructures in glioma.

Depression, a prevalent mental illness, is intricately linked with the neurotransmitters in the brain, while serotonin as a crucial regulator of mood, energy levels, and memory, has been implicated in depression. So, the release of serotonin by serotonergic neurons plays a significant role in the development of depression. Notably, the foremost marker of oxidative stress, hydrogen peroxide (H₂O₂), can interfere with the functioning of serotonergic neurons and potentially contribute to depression. Investigating the impact of H₂O₂ on serotonergic neurons could offer valuable insights into the mechanisms underlying depression. However, there have been no effective tools for selectively imaging H₂O₂ in these neurons so far. To address this gap, we created a small molecular fluorescent probe, PF-H₂O₂, designed specifically for imaging H₂O₂ in serotonergic neurons under oxidative stress. PF-H₂O₂ exerts excellent serotonergic neuron-targetability and notable selectivity for H₂O₂. Furthermore, we discovered increased H₂O₂ in serotonergic neurons of mice with depressive symptoms. Altogether, this endeavour unveils a pioneering tool for exploring pathophysiology linked to serotonergic neuronal dysfunction.

The ability to track altered enzyme activity using a non-invasive imaging protocol is crucial for the early diagnosis of many diseases but is often challenging. Herein, we show that Overhauser magnetic resonance imaging (OMRI) can be used to monitor enzymatic conversion at an ultra-low field (206 μT) using a highly sensitive “off/on” probe with a nitroxide stable radical containing ester, named T2C₁₂–T80. This TEMPO derivative containing probe forms stable electron paramagnetic resonance (EPR) silent micelles in water that are hydrolysed by esterases, thus yielding narrow EPR signals whose intensities correlate directly with specific enzymatic activity. The responsiveness of the probe to tumours, facilitated by increased esterase activity, was initially determined by comparing EPR signals measured upon incubation with 3T3 (healthy fibroblasts used as control), HepG2 (human hepatoma) and Hs766T (human pancreatic cancer cells) cell lysates and then with Hs766T and 3T3 living cells. Next, Overhauser MR images were detected on a phantom containing the probe and the esterases to show that the approach is well suited for being translated to the in vivo detection at the earth's magnetic field. Regarding detection sensitivity, ultra-low field OMRI (ULF-OMRI) is beneficial over OMRI at higher fields (e.g. 0.2 T) since Overhauser enhancements are significantly higher and the technique is safe in terms of the specific absorption rate.

Diabetes mellitus (DM) is a chronic metabolic condition, characterized by hyperglycaemia, oxidative imbalance, pancreatic β-cell death, and insulin insufficiency. Angiotensin II (Ang II) increases oxidative stress, inflammation, and apoptosis, and Ang II type 1 receptor (AT1R) blockers (ARBs) can ameliorate inflammatory response and oxidative stress. However, like other small-molecule drugs, free ARBs show poor in vivo efficacy and dose-limiting toxicities. Hence, in this study, we developed nano-formulations of telmisartan (TEL), an ARB, by encapsulating it inside a murine insulinoma cell-derived extracellular vesicle (nanoTEL) and a bio-mimetic lipid nanovesicle (lipoTEL). Both nano-formulations showed spherical morphology and sustained release of TEL. In vitro, nanoTEL restored oxidative equilibrium, attenuated reactive oxygen species levels, enhanced the uptake of glucose analogue, and increased the expression of glucose transporter protein 4 better than lipoTEL. In a streptozotocin-induced murine model of diabetes, nanoTEL lowered blood glucose levels, improved glucose tolerance, and promoted insulin synthesis and secretion significantly better than lipoTEL. Moreover, nanoTEL was found superior in ameliorating the pancreatic inflammatory microenvironment by regulating NF-κBp65, HIF-1α, and PPAR-γ expression; modulating IL-1β, IL-6, tumor necrosis factor-α, IL-10, and IL-4 levels and inducing the polarization of macrophage from M1 to M2. Further, nanoTEL administration induced angiogenesis and promoted the proliferation of pancreatic cells to restore the structural integrity of the islets of Langerhans more efficiently than lipoTEL. These findings collectively suggest that nanoTEL outperforms lipoTEL in restoring the function of pancreatic β-cells by modulating the pancreatic inflammatory microenvironment and show potential for the treatment of DM.

Despite the biological activity of lactobionic acid (LBA), its low bioavailability remains a challenge in response to complex clinical needs. Aided by computer high-throughput screening and ab initio analysis, we selected betaine and mandelic acid as the right arms to synthesize supramolecular lactobionic acid (SLBA) through a proton exchange reaction, which significantly and comprehensively improved the bioavailability of LBA. Density functional theory and physicochemical characterization revealed the supramolecular characteristics and chemical stability of this coupling. The resulting SLBA has shown significant advantages over LBA in cellular, animal, and clinical trials and demonstrated enormous potential in anti-aging beauty, clinical treatment, biomedicine, and food preservation.

Diabetic wounds are often chronic in nature, and issues like elevated blood sugar, bacterial infections, oxidative stress and persistent inflammation impede the healing process. To ensure the appropriate healing of wounds, scaffolds should promote complete tissue regeneration in wounds, both functionally and structurally. However, the available scaffolds lack the explicit architecture and functionality that could match those of native skin, thus failing to carry out the scar-free skin regeneration in diabetic wounds. This study deals with the synthesis of a bi-layered nanofibrous scaffold mimicking the native skin architecture in terms of porosity and hydrophobic–hydrophilic gradients. In addition, herbal extracts of Aloe vera and litchi honey were added in consecutive layers to manage the high blood glucose level, inflammation, and increased ROS level associated with diabetic wounds. In vitro studies confirmed that the prepared scaffold with herbal extracts showed enhanced proliferation of skin cells with good mechanical strength, degradability, anti-bacterial and anti-diabetic properties. The scaffold also demonstrated superior wound healing in vivo with quicker scar-free wound recovery and appropriate skin regeneration, compared to conventional treatment. Altogether, the synthesized herbal extract loaded bi-layered nanofibrous scaffold can be used as a regenerative template for hard-to-heal diabetic wounds, offering a new strategy for the management of chronic wounds.