Biomedical materials (Bristol, England)最新文献

Integrating biological material within soft microfluidic systems made of hydrogels offers countless possibilities in biomedical research to overcome the intrinsic limitations of traditional microfluidics based on solid, non-biodegradable, and non-biocompatible materials. Hydrogel-based microfluidic technologies have the potential to transformin vitrocell/tissue culture and modeling. However, most hydrogel-based microfluidic platforms are associated with device deformation, poor structural definition, reduced stability/reproducibility due to swelling, and a limited range in rigidity, which threatens their applicability. Herein, we describe a new methodological approach for developing a soft cell-laden microfluidic device based on enzymatically-crosslinked silk fibroin (SF) hydrogels. Its unique mechano-chemical properties and high structural fidelity, make this platform especially suited forin vitrodisease modelling, as demonstrated by reproducing the native dynamic 3D microenvironment of colorectal cancer and its response to chemotherapeutics in a simplistic way. Results show that from all the tested concentrations, 14 wt% enzymatically-crosslinked SF microfluidic platform has outstanding structural stability and the ability to perfuse fluid while displayingin vivo-like biological responses. Overall, this work shows a novel technique to obtain an enzymatically-crosslinked SF microfluidic platform that can be employed for developing soft lab-on-a-chipin vitromodels.

Controlled drug release systems are pivotal in optimizing therapeutic outcomes and mitigating side effects in treatment protocols. While traditional delivery vectors such as liposomes, micro/nanoparticles, and microspheres are effective, they often struggle with consistency in drug release rates. This study addresses these issues by integrating stimuli-responsive elements specifically magnetic, thermal, and pH-responsive components into drug delivery systems for precise control. Central to our approach is the use of silk fibroin (SF), chosen for its superior biocompatibility and tunable degradation kinetics. We developed uniform carrier microspheres (CMs) by embedding polydopamine nanoparticles (PDA NPs) into SF microspheres using a custom-designed microfluidic platform. The development process and the application of this platform are detailed, highlighting the precision in control achievable. These CMs showcased enhanced photothermal effects, with the thermal response finely adjustable by altering the PDA NPs concentration, achieving a notable temperature increase of 24.5°C at 7.4 wt% concentration. High drug loading capacity (7.5%) and encapsulation efficiency (91.6%) were achieved, along with a pH-responsive release profile under near-infrared irradiation, paving the way for targeted anticancer drug delivery systems using the model drug doxorubicin hydrochloride. These findings underscore the potential of the developed CMs for external topical application, offering promising prospects for targeted cancer therapy utilizing drug-loaded microspheres.

The present study has been designed to fabricate fungal endophyte-assisted gold nanoparticles (AuNPs) and elucidate their anti-breast cancer potential. The aqueous extract of fungal endophytePenicillium oxalicum(PO), associated with the medicinal plantAmoora rohituka, was used for the fabrication of AuNPs (POAuNPs). Physico-chemical characterization using Ultraviolet-visible spectroscopy, Fourier transform infrared, X-ray diffraction, Dynamic light scattering, Zeta potential, Transmission electron microscopy and Field emission scanning electron microscopy analysis revealed stable, uniform distribution, spherical shape and crystalline nature of POAuNPs with a size range of 3-46 nm. Furthermore, the POAuNPs potentially inhibited the growth of pathogenic bacterial strainsEscherichia coliandStaphylococcus aureus. The synthesized POAuNPs have shown potential antioxidant effects against 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide and nitric oxide (NO) radical scavenging assays with an EC₅₀value of 8.875 ± 0.082, 52.593 ± 2.506 and 43.717 ± 1.449 µg mL^-1, respectively. Moreover, the value of EC₅₀for the total antioxidant capacity of POAuNPs was found to be 23.667 ± 1.361 µg mL^-1. The cell viability of human breast cancer cells, MDA-MB-231 and MCF-7, was found to be reduced after treatment with POAuNPs, and IC₅₀values were found to be 19.753 ± 0.640 and 35.035 ± 0.439 µg mL^-1, respectively. Further,in vitrobiochemical assays revealed that POAuNPs induces metabolic reprogramming in terms of reduced glucose uptake, increased lactate dehydrogenase (LDH) release and, disruption of oxidative balance through depletion of glutathione levels, increased nitric oxide (NO) and lipid peroxidation levels as a possible pathway to suppress human breast cancer cell proliferation. Apoptosis-specific nuclear modulations induced by POAuNPs in human breast cancer cells were validated through 4',6-diamidino-2-phenylindole (DAPI) nuclear staining. The present investigation thus attempts to show the first ever fabrication of AuNPs using an aqueous extract ofP. oxalicumassociated withA. rohituka. The results revealed unique physico-chemical characteristics of mycogenic AuNPs, and screening their effect against breast cancer via metabolic reprogramming and induction of apoptosis thus adds great significance for cancer therapeutics, suggesting further exploration to develop nanotherapeutic drugs.

The pursuit of sustainable bioinspired materials for regenerative medicine demands a nuanced balance between scientific advancement, ethical considerations, and environmental consciousness. This abstract encapsulates a comprehensive perspective paper exploring the intricate dynamics of toxicology, environmental impact, and ethical concerns within the realm of bioinspired materials. As the landscape of regenerative medicine evolves, ensuring the biocompatibility and safety of these materials emerges as a pivotal challenge. Our paper delves into the multidimensional aspects of toxicity assessment, encompassing cytotoxicity, genotoxicity, and immunotoxicity analyses. Additionally, we shed light on the complexities of evaluating the environmental impact of bioinspired materials, discussing methodologies such as life cycle assessment, biodegradability testing, and sustainable design approaches. Amid these scientific endeavors, we emphasize the paramount importance of ethical considerations in bioinspired material development, navigating the intricate web of international regulations and ethical frameworks guiding medical materials. Furthermore, our abstract underscores the envisioned future directions and challenges in toxicology techniques, computational modeling, and holistic evaluation, aiming for a comprehensive understanding of the synergistic interplay between sustainable bioinspired materials, toxicity assessment, environmental stewardship, and ethical deliberation.

Magnesium ions play an important immune-regulatory role during bone repair. For this study, we prepared micro-nano bioactive glass (MNBG) containing magnesium, which can release magnesium, silicon, and calcium ions and has a positive impact on osteogenic differentiation and vascular regeneration. In this study, MgMNBG was compounded and combined with poly(lactic-co-glycolic acid (PLGA) and polycaprolactone (PCL) for 3D printing. Afterwards, the physicochemical properties and bone repair performance of the scaffolds were evaluated throughin vitroandin vivoexperiments. We also investigated the effects of MgMNBG on osteogenic differentiation, immune regulation, and vascular regeneration. The results showed that MgMNBG can inhibit inflammation and promote osteogenesis and angiogenesis by regulating macrophages. PLGA/PCL/MgMNBG scaffolds have good osteogenic and angiogenic effects, and the composite scaffolds have excellent bone repair performance and potential application value.

Chemodynamic therapy (CDT) is a new method for cancer treatment that produces highly toxic reactive oxygen species (ROS) in the tumor microenvironment to induce cancer cell apoptosis or necrosis. However, the therapeutic effect of CDT is often hindered by intracellular H₂O₂deficiency and the activity of antioxidants such as glutathione (GSH). In this study, a nano-catalyst HCM was developed using a self-assembled Cu/Mn-doped metal-organic framework, and its surface was modified with hyaluronic acid to construct a tumor-targeting CDT therapeutic agent with improved the efficiency and specificity. Three substances HHTP (2, 3, 6, 7, 10, 11-hexahydroxybenzophenanthrene), Cu²⁺, and Mn²⁺were shown to be decomposed and released under weakly acidic conditions in tumor cells. HHTP produces exogenous H₂O₂in the presence of oxygen to increase the H₂O₂content in tumors, Cu²⁺reduces GSH content and generates Cu⁺in the tumor, and Cu⁺and Mn²⁺catalyze H₂O₂to produce ∙OH in a Fenton-like reaction. Together, these three factors change the tumor microenvironment and improve the efficiency of ROS production. HCM showed selective and efficient cytotoxicity to cancer cells, and could effectively inhibit tumor growthin vivo, indicating a good CDT effect.

This paper describes the extrusion pressure's effect on composite hydrogel inks' filaments subjected to three point bending collapse tests. The composite considered in this work consists of an alginate-poloxamer hydrogel reinforced with flax fibres. Increased extrusion pressure resulted in more asymmetrical filaments between the support pillars. Furthermore, the material and printing conditions used in the present study led to the production of curved specimens. These two characteristics implicitly limit the validity of the yield stress equations commonly used in open literature. Therefore, a new system of equations was derived for the case of asymmetrical and curved filaments. A post-processing method was also created to obtain the properties required to evaluate this yield stress. This new equation was then implemented to identify the strength of failed hydrogels without flax fibre reinforcement. A statistical analysis showed this new equation's significance, which yielded statistically higher (i.e. 1.15 times larger) strength values compared to the numbers obtained with the open literature equations. At larger extrusion pressures, longer periods were needed for the material to converge towards its final shape. Larger extrusion pressure values led to lower yield stresses within the composite hydrogel filament: a 5 kPa increase in extrusion pressure lowered the yield stress by 19%. In comparison, a 15 kPa increase led to a 29% decrease in the yield stress. Overall this study provides guidelines to standardize three point bending collapse tests and analysis comparison between different materials.

Pharmacokinetics of nanomedicines can be improved by a temporal blockade of mononuclear phagocyte system (MPS) through the interaction with other biocompatible nanoparticles. Liposomes are excellent candidates as blocking agents, but the efficiency of the MPS blockade can greatly depend on the liposome properties. Here, we investigated the dependence of the efficiency of the induced MPS blockadein vitroandin vivoon the size of blocking liposomes in the 100-500 nm range. Saturation of RAW 264.7 macrophage uptake was observed for phosphatidylcholine/cholesterol liposomes larger than 200 nmin vitro. In mice, liposomes of all sizes exhibited a blocking effect on liver macrophages, prolonging the circulation of subsequently administrated magnetic nanoparticles in the bloodstream, reducing their liver uptake, and increasing accumulation in the spleen and lungs. Importantly, these effects became more pronounced with the increase of liposome size. Optimization of the size of the blocking liposomes holds the potential to enhance drug delivery and improve cancer therapy.

The preparation of cells is a critical step in cell therapy. To ensure the effectiveness of cells used for clinical treatments, it is essential to harvest adherent cells from the culture media in a way that preserves their high viability and full functionality. In this study, we developed temperature-responsive poly(N-isopropylacrylamide) (PNIPAM)-grafted polystyrene (PS) microspheres using reversible addition-fragmentation chain transfer polymerization. These microspheres allow for the non-destructive harvesting of cultured cells through temperature changes. The composition and physicochemical properties of the PNIPAM-grafted PS microspheres were confirmed using infrared spectroscopy, elemental analysis, dynamic light scattering, and thermogravimetric analysis.In vitroexperiments demonstrated that these microspheres exhibit excellent biocompatibility, supporting the adhesion and proliferation of various cells. Moreover, the microspheres showed good temperature responsiveness in thermosensitive detachment experiments with GFP-HepG₂cells and umbilical cord mesenchymal stem cells (UC-MSCs). Additionally, through orthogonal experiments, we identified a cell detachment aid mixture that significantly improved the dispersibility of cells detached from the microspheres, enhancing the efficiency of thermosensitive cell detachment by approximately 40%. The harvested UC-MSCs retained their capacity for re-proliferation and trilineage differentiation. Consequently, the temperature-responsive microspheres developed in this study, combined with the cell detachment aid mixtures, hold great potential for large-scale culture and harvesting of therapeutic cells in clinical applications.

Polylysine-based composites have emerged as promising materials in biomedical applications due to their versatility, biocompatibility, and tunable properties. In drug delivery, polylysine-based composites furnish a novel platform for targeted and controlled release of therapeutic agents. Their high loading capacity and capability to encapsulate diverse drugs make them ideal candidates for addressing challenges such as drug stability and controlled release kinetics. Additionally, their biocompatibility ensures minimal cytotoxicity, vital for biomedical applications. They also hold substantial potential in tissue engineering by providing a scaffold with tunable mechanical characteristics and surface properties, and can support cell adhesion, proliferation, and differentiation. Furthermore, their bioactive nature facilitates cellular interactions, promoting tissue regeneration and integration. Wound healing is another area where polylysine-based composites show promise. Their antimicrobial properties help prevent infections, while their ability to foster cell migration and proliferation accelerates the wound healing procedure. Incorporation of growth factors or other bioactive molecules further enhances their therapeutic effectiveness. In biosensing applications, they serve as robust substrates for immobilizing biomolecules and sensing elements. Their high surface area-to-volume ratio and excellent biocompatibility improve sensor sensitivity and selectivity, enabling accurate detection of biomarkers or analytes in biological samples. Polylysine-based composites offer potential as contrast agents in bioimaging, aiding in diagnosis and monitoring of diseases. Overall, polylysine-based composites represent a versatile platform with diverse applications in biomedical research and clinical practice, holding great promise for addressing various healthcare challenges. .