Advanced Healthcare Materials最新文献

Nowadays, gastroesophageal reflux disease (GERD) has emerged as one of the major hazards to the health of the upper gastrointestinal tract, and there is an urgent need for a low-cost, user-friendly, and non-invasive detection method. Herein, a paper-based sensor (CP sensor) for the non-invasive screening of GERD is proposed. The sensor is structured as a specially shaped cellulose paper strip embedded with fluorescent colloids, which are self-assembled from a cleavable synthetic fluorescent polymer (P4). Benefiting from the introduction of amide bonds and the unique assembled structure of the nanocolloids, the pepsin in the sample solution will hydrolyze the water-soluble branches in the micellar shell during detection, resulting in a corresponding output of the fluorescent signal. This responsiveness, which can be observed by the naked eye, is so sensitive with a minimum detectable concentration for pepsin as low as 0.3 ng·mL^-1. Clinical trials have further demonstrates that the designed paper sensor is capable of providing improved accuracy in the early diagnosis of GERD.

Implantable drug delivery systems are crucial for achieving sustained delivery of active compounds to specific sites or systemic circulation. In this study, a novel reservoir-type implant combining a biodegradable rate-controlling membrane with a drug-containing core prepared using direct compression techniques is developed. The membrane is composed of poly(caprolactone) (PCL), and risperidone (RIS) served as the model drug. Characterization of both membranes and direct compressed pellets includes hardness testing, optical coherence tomography, mercury intrusion porosimetry, and surface morphology observation. In vitro release studies of RIS reveal that higher drug loading in the pellets extended-release duration up to 70 days when incorporated into membranes with four layers. Increasing the number of membrane layers slows the release rate further, ranging from 70 to 170 days depending on membrane thickness. Biocompatibility studies demonstrate that these implantable devices are non-toxic and biocompatible with cells in vitro. In vivo studies conduct in male Wistar rats demonstrate sustained release of RIS, with plasma levels showing a significant increase post-implantation at a relatively constant rate for up to 49 days. These results indicate that the developed implants have the potential to provide long-acting drug delivery to the systemic circulation.

Facilitating neuronal differentiation of stem cells and microenvironment remodeling are the key challenges in cell-based transplantation strategies for central nervous system regeneration. Herein, the study harnesses the intrinsic pro-neural differentiation potential of nerve-derived extracellular matrix (NDEM) and its specific affinity for cytokines to develop an NDEM-gelatin methacryloyl(gelMA)-based bifunctional hydrogel delivery system for stem cells and cytokines. This system promotes the neural differentiation of bone marrow stromal cells (BMSCs) and optimizes the therapeutic index of Interleukin-4 (IL-4) for spinal cord injury (SCI) treatment. It is observed that incorporating NDEM into the hydrogel system intrinsically promotes BMSC differentiation into neuron-like cells and effectively regulates IL-4 release kinetics to match the neural reconstructing timeframe. Further analysis reveals that trace amounts of endogenous basic fibroblast growth factor (bFGF) detected in NDEM exhibit a potent effect in promoting neural differentiation. The sustained release of IL-4 from the NDEM significantly encourages macrophage polarization toward the M2 phase, optimizing the transplant microenvironment throughout the reconstruction process. This study demonstrates an NDEM-based optimization strategy for hybrid hydrogel to achieve synchronized delivery of stem cells and cytokines in regenerative medicine applications.

Aging is one of the most significant risk factors for breast cancer. With the growing interest in the alterations of the aging breast tissue microenvironment, it is identified that aging is related to tumorigenesis, invasion, and drug resistance. However, current pre-clinical disease models often neglect the impact of aging and sometimes result in worse clinical outcomes. In this study, aged animal-generated materials are utilized to create and validate a novel age-mimetic breast cancer model that generates an aging microenvironment for cells and alters cells toward a more invasive phenotype found in the aged environment. Furthermore, the age-mimetic models are utilized for 3D breast cancer invasion assessment and high-throughput screening of over 700 drugs in the FDA-approved drug library. 36 potential effective drug targets as well as 34 potential drug targets with different drug responses in different age groups are identified, demonstrating the potential of this age-mimetic breast cancer model for further in-depth breast cancer studies and drug development.

Dental resin-based restorative (RBR) materials represent the most ubiquitous biomaterials utilized globally. Methacrylate (MA)-ester based monomers - present in RBRs since the 1960s - experience significantly elevated rates of failure compared to previously used silver/amalgam fillings attributed to their hydrolysis reported in both simulated and in vivo environments. There is currently no alternative RBR chemistry that matches the functional and clinical workflow considerations of MA-RBRs while addressing their limited-service lives. The objective of this work is to utilize a systematic framework to develop alternative hydrolytically-stable monomers (HSMs), assessing key physical properties, biostability, and cytocompatibility towards eliminating or reducing the biodegradation of RBRs. This process yielded HSMs (referreed to as 3BE, 3TE) that matched the physical properties of MA-control materials, including viscosity, polymerization conversion, hydrophilicity, water uptake, and surface hardness (p > 0.05), while outperforming MA-based materials in all simulated oral environments, showing improved biostability in reconstituted human saliva, simulated human salivary esterase (SHSE), bacterial culture, and acidic media (p < 0.05). Additionally, HSMs were found to be less cytotoxic than commercial MA-monomers (p < 0.05) and unlikely to be genotoxic. Therefore, the HSMs and associated resins developed in this study have the potential to significantly improve the clinical service life of RBRs, without compromising their fundamental features.

Uncontrollable haemorrhage and associated microbial contamination in the battlefield and civilian injuries pose a tremendous threat to healthcare professionals. Such traumatic wounds often necessitate an effective point-of-care solution to prevent the consequent morbidity owing to blood loss or haemorrhage. However, developing superior hemostatic materials with anti-infective properties remains a challenge. To address this, an injectable, cationic dextran-mesoporous silica nanoparticle-based bactericidal hemostatic sponge (BACSTAT) has been developed. A dual crosslinking approach is adopted through in situ covalent cross-linking through photo polymerization and silica nanoparticle-induced non-covalent interactions. This interconnected macroporous BACSTAT sponge has superior fluid absorption properties and fluid-induced rapid shape recovery of the sponge helps to seal the irregularly shaped wound. Furthermore, this sponge can stimulate a coagulation cascade for rapid blood clotting in mice femoral vein incision and liver puncture model. The optimum sponge exhibited potent antibacterial activity against wide-spectrum Gram-positive and Gram-negative pathogens. Notably, it is completely biocompatible with mammalian cells and mice skin. Significantly, this sponge reduces Pseudomonas aeruginosa burden >99% in mice subcutaneous infection model with substantially lessening inflammatory responses in infected tissues. Collectively, the optimized sponge bears immense potential to be developed as point-of-care solution for military and civilian traumatic injury.

Immune cells show enormous potential for targeted nanoparticle delivery due to their intrinsic tumor-homing skills. However, the immune cells can internalize the nanoparticles, leading to cellular functional impairments, degradation of the nanoparticles, and delayed release of drugs from the immune cells. To address these issues, this study introduces an approach for the synthesis of freshly derived neutrophils (NUs)-based nanocarriers system where the NUs are surfaced by dialdehyde alginate-coated self-assembled micelles loaded with mitoxantrone (MIT) and indocyanine green (ICG) (i.e., dA(MI@IPM)s) for stimuli-responsive tumor-targeted therapy. Here, the dA(MI@IPM)s are not internalized by the NUs, but they are anchored on the membrane of the NUs via distearoylphosphatidylethanolamine-polyethylene glycol-polyethylenimine anchors. Owing to the natural recruitment ability of NUs to the tumor microenvironment, NUs-anchored dA(MI@IPM)s accumulation is higher at the tumor site than free dA(MI@IPM)s, where the dA(MI@IPM)s can readily detach from the NUs to get internalized in the tumor cells. The stimuli-responsive dA(MI@IPM)s disassembles inside the cancer cells upon near-infrared irradiation due to the photosensitizing effect of the loaded ICG, releasing MIT and significantly inhibiting tumor growth. This approach is simple and fast to prepare, opening up exciting possibilities for personalized cancer treatment using patient's autologous NUs.

Toward the aim of reducing animal testing, innovative in vitro models are required. Here, this study proposes a novel smart polymeric microscaffold to establish an advanced 3D model of dopaminergic neurons. These scaffolds are fabricated with Ormocomp via Two-Photon Polymerization. The scaffolds are further enhanced by functionalization with fluorescent nanodiamonds (FNDs), which can serve as quantum nanosensors for both magnetic and temperature sensing. The material biocompatibility is tested using two different cell lines, SH-SY5Y and A431, with cell viability over 98%. A total of 69% of the FNDs are grafted on the structure compared to those that remained on the glass surface. Cells are tested with the scaffolds in several microenvironments, and the final assembly required for 3D quantum metrology experiments achieved 91% biocompatibility. Subsequently, embryoid bodies containing dopaminergic neurons, the cell type affected by Parkinson's disease (PD), are integrated with FND-functionalized scaffolds. This 3D model is successfully established, demonstrated by strong interactions between dopaminergic neurons and the scaffold, with the directional growth of neurites along the 3D scaffold. Ultimately, this study have developed a 3D platform that enables the readout of signaling in a model that holds great potential for future PD research.

Surface-mediated transmission of pathogens plays a key role in healthcare-associated infections. However, proper techniques for its quantitative analysis are lacking, making it challenging to develop novel antimicrobial and anti-fouling surfaces to reduce pathogen spread via environmental surfaces. This study demonstrates a gelatin hydrogel-based touch transfer test, the HydroTouch test, to evaluate pathogen transmission on high-touch surfaces under semi-dry conditions. The HydroTouch test employs gelatin as a finger mimetic, facilitating testing with pathogenic bacteria under controlled conditions. The thermoresponsive sol-gel transition of gelatin allows easy recovery and quantification of bacteria before and after testing. The HydroTouch test demonstrates that methicillin-resistant Staphylococcus aureus has a high transmission efficiency of ≈16% onto stainless steel, compared to <3% for Escherichia coli or Pseudomonas aeruginosa. Polyurethane surfaces exhibit strong resistance to bacterial contamination with a transmission efficiency of ≈0.6%, while polytetrafluoroethylene shows a transmission efficiency approximately four times higher than polyurethane. Additionally, quaternary ammonium-based antimicrobial coatings reduce the transmission efficiency of live bacteria on stainless steel to ≈4% of the original level. The HydroTouch test provides a reliable method for assessing pathogen transmission on various surfaces under semi-dry settings, supporting the development of effective antimicrobial, anti-transmission coatings to reduce healthcare-associated infections.

Myocarditis, a leading cause of sudden cardiac death and heart transplantation, poses significant treatment challenges. The study of clinical samples from myocarditis patients reveals a correlation between the pathogenesis of myocarditis and cardiomyocyte mitochondrial DNA (mtDNA). During inflammation, the concentration of mtDNA in cardiomyocytes increases. Hence, it is hypothesized that the combined clearance of mtDNA and its downstream STING pathway can treat myocarditis. However, clearing mtDNA is problematic. An innovative mtDNA scavenger is introduced, Nanosweeper (NS), which utilizes its nanostructure to facilitate the transport of NS-mtDNA co-assemblies for degradation, achieving mtDNA clearance. The fluorescent mtDNA probe on NS, bound to functional peptides, enhances the stability of NS. NS also exhibits robust stability in human plasma with a half-life of up to 10 hours. In a murine myocarditis model, NS serves as a drug delivery vehicle, targeting the delivery of the STING pathway inhibitor C-176 to the myocardium. This approach synergistically modulates the cGAS-STING axis with NS, effectively attenuating myocarditis- associated inflammatory cascade. This evaluation of NS in porcine models corroborated its superior biosafety profile and cardiac targeting capability. This strategic approach of targeted mtDNA clearance couple with STING pathway inhibition, significantly augments therapeutic efficacy against myocarditis, outperforming the conventional drug C-176, indicating its clinical potential.