Journal of materials chemistry. B最新文献

Recent advancements in tissue engineering and regenerative medicine have introduced promising strategies to address tissue and organ deficiencies. This review highlights the critical role of short peptides, particularly their ability to self-assemble into matrices that mimic the extracellular matrix (ECM). These low molecular weight peptides exhibit target-specific activities, modulate gene expression, and influence cell differentiation pathways. They are stable, programmable, non-cytotoxic, biocompatible, biodegradable, capable of crossing the cell membrane and easy to synthesize. This review underscores the importance of peptide structure and concentration in directing stem cell differentiation and explores their diverse biomedical applications. Peptides such as Aβ1-40, Aβ1-42, RADA16, A13 and KEDW are discussed for their roles in modulating stem cell differentiation into neuronal, glial, myocardial, osteogenic, hepatocyte and pancreatic lineages. Furthermore, this review delves into the underlying signaling mechanisms, the chemistry and design of short peptides and their potential for engineering biocompatible materials that mimic stem cell microenvironments. Short peptide-based biomaterials and scaffolds represent a promising avenue in stem cell therapy, tissue engineering, and regenerative medicine.

Tissue regeneration after a wound occurs through three main overlapping and interrelated stages namely inflammatory, proliferative, and remodelling phases, respectively. The inflammatory phase is key for successful tissue reconstruction and triggers the proliferative phase. The macrophages in the non-healing wounds remain in the inflammatory loop, but their phenotypes can be changed via interactions with nanofibre-based scaffolds mimicking the organisation of the native structural support of healthy tissues. However, the organisation of extracellular matrix (ECM) is highly complex, combining order and disorder, which makes it difficult to replicate. The possibility of predicting the desirable biomimetic geometry and chemistry of these nanofibre scaffolds would streamline the scaffold design process. Fifteen families of nanofibre scaffolds, electrospun from combinations of polyesters (polylactide, polyhydroxybutyrate), polysaccharides (polysucrose, carrageenan, cellulose), and polyester ether (polydioxanone) were investigated and analysed using machine learning (ML). The Random Forest model had the best performance (92.8%) in predicting inflammatory responses of macrophages on the nanoscaffolds using tumour necrosis factor-alpha as the output. CellProfiler proved to be an effective tool to process scanning electron microscopy (SEM) images of the macrophages on the scaffolds, successfully extracting various features and measurements related to cell phenotypes M0, M1, and M2. Deep learning modelling indicated that convolutional neural network models have the potential to be applied to SEM images to classify macrophage cells according to their phenotypes. The complex organisation of the nanofibre scaffolds can be analysed using graph theory (GT), revealing the underlying connectivity patterns of the nanofibres. Analysis of GT descriptors showed that the electrospun membranes closely mimic the connectivity patterns of the ECM. We conclude that ML-facilitated, GT-quantified engineering of cellular scaffolds has the potential to predict cell interactions, streamlining the pipeline for tissue engineering.

High drug resistance remains a challenge for chemotherapy against hepatocellular carcinoma (HCC). Combining chemotherapeutic agents with microRNA (miRNA), which simultaneously regulates multiple pathways, offers a promising approach to improve therapeutic efficacy against HCC. Although cationic amphiphilic copolymers have been used to co-deliver these agents, their effectiveness is often limited by low co-encapsulation efficiency and inherent cationic toxicity. In this study, we developed a facile approach to co-deliver doxorubicin (DOX) and miRNA-26a (miR-26a) using a non-cationic nanogel. The incorporation of an amphiphilic monomer and a lysosomal enzyme-sensitive crosslinker endows the nanomedicine with several advantages, including high co-encapsulation efficiency, lysosomal escape, and minimal toxicity. miR-26a significantly increased the sensitivity of HCC to DOX by 3.35-fold through targeting multiple pathways, and promoted DOX penetration within tumor tissue through reducing type I collagen content, thereby showing significant synergistic anticancer effects. This study provides a facile and biosafe nanoplatform for the efficient co-delivery of DOX and miRNA with synergistic drug effect.

Infections caused by fungal pathogens are a global health problem, and have created an urgent need for new antimicrobial strategies. This report details the synthesis of lipidated 2-vinyl-4,4-dimethyl-5-oxazolone (VDM) oligomers via an optimized Cu(0)-mediated reversible-deactivation radical polymerization (RDRP) approach. Cholesterol-Br was used as an initiator to synthesize a library of oligo-VDM (degree of polymerisation = 5, 10, 15, 20, and 25), with an α-terminal cholesterol group. Subsequent ring-opening of the pendant oxazolone group with various functional amines [i.e., 2-(2-aminoethyl)-1,3-di-Boc-guanidine (BG), 1-(3-aminopropyl)imidazole (IMID), N-Boc-ethylenediamine (BEDA), or N,N-dimethylethylenediamine (DMEN)] yielded an 11 functional cationic lipidated oligomer (CLOs) library, which comprised different cationic elements with the same terminal lipid cholesterol element. These CLOs exhibited greater activity against all tested fungal pathogens (Candida albicans, Cryptococcus neoformans, Candida tropicalis, Candida glabrata, Cryptococcus deuterogattii, and Candida auris), compared to the bacterial pathogens (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus [MRSA]). Specifically, the DMEN and BEDA (after deprotection) series exhibited superior antifungal activities 4-16 times greater [determined by the minimum inhibitory concentration (MIC) in μg mL^-1] than the clinically relevant antifungal fluconazole. Two 'hit' CLOs (Chol-DMEN-25 and Chol-BEDA-10) were identified, which inhibited both single sp. (C. albicans, C. tropicalis, C. neoformans, or C. gattii) and dual sp. (C. albicans and C. tropicalis) biofilm formation, and were able to attenuate mature biofilms, with a >50% mature biofilm biomass reduction at 128 μg mL^-1. Co-delivery of fluconazole with two 'hit' CLOs demonstrated additive and synergistic effects on the aforementioned single-species and dual-species fungi biofilms, with a synergy score (SS) ranging from ∼3 to 15 and most synergistic area score (MSAS) ∼13-29 (by a Bliss independence model). The mechanistic studies (PI assay and nucleic acid release assay) revealed that these CLOs disrupted the integrity of fungal cell membranes. These results demonstrate that cholesterol terminated CLOs are potential antifungal candidates.

Sulfur-containing small molecules, mainly including cysteine (Cys), homocysteine (Hcy), glutathione (GSH), and hydrogen sulfide (H₂S), are crucial biomarkers, and their levels in different body locations (living cells, tissues, blood, urine, saliva, etc.) are inconsistent and constantly changing. Therefore, it is highly meaningful and challenging to synchronously and accurately detect them in complex multi-component samples without mutual interference. In this work, we propose a steric hindrance-regulated probe, NBD-2FDCI, with single excitation dual emissions to achieve self-adaptive detection of four analytes. This probe was meticulously designed and constructed from a pK_a-tuned 2FDCI fluorophore and a thiol-specific recognition moiety NBD. Except for 661 nm fluorescence for indicating the total biothiols and H₂S, Cys and Hcy could trigger an additional 550 nm fluorescence. Utilizing the distinctive responses, the probe NBD-2FDCI exhibited exclusive linear ranges for GSH, Cys/Hcy, and H₂S to avoid high-level component interference. Thus, the probe was then applied for sulfur compound measurements in urine samples, indicating metabolic disorder of Cys and H₂S in bladder cancer patients. Moreover, adaptive imaging of probe NBD-2FDCI in cells was performed with the results being consistent with in vitro testing. In a word, spatial hindrance strategy-guided probes may exhibit broader prospects in the detection of similar components in complex samples.

Adjuvants can enhance an immunological response, which is an important part of vaccine research. Pickering bubbles have been a mega-hit for biomedical applications, including in vivo visualization and targeted drug delivery. However, there have been no studies on Pickering bubbles as an immunological adjuvant, and the special properties and structures of Pickering bubbles may play an important role in immunization. In this study, poly(lactic-co-glycolic acid) (PLGA) particles were used to construct nanoparticle-stabilized Pickering bubbles (PPBs). PPBs were evaluated as immunological adjuvants based on immune response effects and mechanisms and aiming at future applications. PPBs have a flexible gas core and a special surface structure that can increase the cell contact area to promote phagocytosis and enhance the immune response. Quartz crystal microbalance with dissipation (QCM-D) data showed the flexibility of PPBs, and confocal images captured the deformability of PPBs during cell uptake. Flow cytometry and antibody titer detection showed that PPBs significantly promoted antigen uptake and activation of bone-marrow-derived dendritic cells (BMDCs) and induced an immune response with upregulated SIINFEKL MHC I and CD127 molecules on the surface of CD8⁺ T cells, indicating excellent antigen cross-presentation and cellular immune triggering effects. The upregulation of CD44 and CD62L on CD4⁺ T cells and the IgG2a/IgG1 ratio bias further demonstrated the excellent adjuvant role of PPBs in immunity. Finally, the biosafety of PPBs as an immunological adjuvant was also demonstrated. Our study demonstrates the potential of particle-stabilized bubbles as immune adjuvants, which provides innovative ideas for vaccine development and design.

Bioabsorbable metallic alloys constitute a very challenging and innovative field, mainly aimed to develop the next generation of temporary medical implants. Degradation data, biological in vitro and in vivo tests are of major importance in particular for complex alloys, in which the individual element additions could enhance material performance and add functionalities. In this study, a novel Fe-Mn-Si-Cu alloy was carefully designed for vascular and blood-contact applications, and its microstructure, mechanical behavior, degradation behavior and biological performances were investigated accordingly. In previous studies, Mn and Si were found to be suitable elements to effectively enhance mechanical properties and accelerate corrosion rate in simulated body fluid. Cu was added for further grain refinement by the formation of small Cu-rich particles, potentially impacting mechanical properties and degradation behavior. In addition, the feasibility of inducing antibacterial effects in a Fe-Mn-Si-Cu alloy with low Cu content was investigated. The alloy was prepared firstly on a small scale by vacuum arc remelting, then on a larger scale by vacuum induction melting and converted into sheets by conventional thermomechanical processing techniques. Heat treatments were explored to find optimal microstructure conditions. The results confirm promising mechanical, degradation and biological performance in testing the material in in vitro conditions, showing that the degradation products are neither systematically cytotoxic nor have any hemotoxic effects. On the other hand, the expected antibacterial effects could not be confirmed.

Diabetes remains one of the most prevalent chronic diseases globally, significantly impacting mortality ratetables. The development of effective treatments for controlling glucose level in blood is critical to improve the quality of life of patients with diabetes. In this sense, smart optical sensors using hydrogels, responsive to external stimuli, have emerged as a revolutionary approach to diabetes care. In this study, changes in the optical properties of a hydrogel are employed for monitoring α-glucosidase activity, a critical enzyme involved in diabetes mellitus type II due to its role in breaking terminal α-glycosidic bonds, releasing α-glucose. The enzyme is encapsulated within a triazine-based hydrogel that exhibits intrinsic blue fluorescence. Upon hydrolysis of the substrate p-nitrophenyl-α-D-glucopyranoside (p-NPG) by α-glucosidase, the fluorescence is quenched due to the release of p-nitrophenol (PNP). However, when exposed to potential antidiabetic drugs, the enzyme's activity is inhibited, and the hydrogel's fluorescence remains intact. This ON/OFF fluorescence-based assay enables rapid screening of drug candidates by evaluating their ability to inhibit α-glucosidase enzymatic activity. Sensor optimization involves conducting swelling studies, fluorescent assays, reusability tests and a trial with a real antidiabetic drug. This innovative approach holds potential for enhancing antidiabetic drug screening and management, offering a more accessible and efficient solution compared to traditional biosensors.

Imazaquin (IMQ) is an imidazolinone group herbicide widely used for weed control around the world. Due to excessive use during crop production, IMQ can accumulate in corn and soybeans, positing a potential threat to human health. In this study, a hapten that had high specificity and sensitivity was designed using computer-simulated technology. A monoclonal antibody (mAb) was synthesized with a half inhibitory concentration of 0.98 ng mL^-1. The mAb was incorporated into an immunochromatographic assay (ICA) for the detection of IMQ in corn and soybeans. The visual limit of detection was 10 μg kg^-1 in corn with a linear range of 3.85-208.26 μg kg^-1 and 5 μg kg^-1 in soybeans with a linear range of 3.78-106.71 μg kg^-1. Additionally, the ICA strips had excellent recovery rates, and the results were confirmed by liquid chromatography tandem mass spectrometry. Our study developed a method for the rapid on-site detection of IMQ residues in corn and soybeans.

With the miniaturization, integration and intelligence of sweat electrochemical sensor technology, hydrogel flexible sensors have demonstrated immense potential in the field of real-time and non-invasive personal health monitoring. However, it remains a challenge to integrate excellent mechanical properties, self-healing properties, and electrochemical sensing capabilities into the preparation of hydrogel-based flexible sensors. The utilization of CBPG (cellulose nanocrystals (CNCs)@bovine serum albumin (BSA)@polyethyleneimine (PEI) glucose oxidase (GOD) nanomaterial) as both an enhancing phase and sensor probe within a hydrogel matrix, with poly(vinyl alcohol) (PVA) serving as the primary network constituent, has been proposed as a non-invasive technique for monitoring trace glucose levels in sweat. In this study, BSA was initially attached to CNCs through electrostatic interactions. To further boost the surface active sites of the nanomaterial (CNCs@BSA), PEI was grafted onto the nanomaterial surface. The resulting CNC@BSA@PEI nanomaterials were then used as carriers for GOD. The prepared hydrogel exhibited good self-healing properties (87.5%) and excellent breaking strength (0.8 MPa), effectively converting glucose stimulation in human sweat into electrical output. The sensor had a detection range of 1.0-100.0 μM and a detection limit as low as 0.9 μM. Due to its ability to specifically recognize trace glucose levels in sweat, the CBPG-PVA sensor can perform highly selective, flexible, and reliable real-time monitoring of human sweat, offering significant potential for wearable biofluid monitoring in personalized health applications.