ACS Biomaterials Science & Engineering最新文献

Electroactive microorganisms such as Geobacter sulfurreducens can couple organic electron donor oxidation to the respiration of electrode surfaces, colonizing them in the process. These microbes can also reduce soluble metal ions, such as soluble Pd, resulting in metallic nanoparticle (NP) synthesis. Such NPs are valuable catalysts for industrially relevant chemical production; however, their chemical and solid-state syntheses are often energy-intensive and result in hazardous byproducts. Utilizing electroactive microbes for precious metal NP synthesis has the advantage of operating under more sustainable conditions. By combining G. sulfurreducens's ability to colonize electrodes and synthesize NPs, we performed electrode cultivation ahead of biogenic Pd NP synthesis for the self-assembled fabrication of a cell-Pd biomaterial. G. sulfurreducens biofilms were grown in electrochemical reactors with added soluble Pd, and electrochemistry, spectroscopy, and electron microscopy were used to confirm (1) metabolic current production before and after Pd addition, (2) simultaneous electrode respiration and soluble Pd reduction over time, and (3) biofilm-localized Pd NP synthesis. Utilizing electroactive microbes for the controlled synthesis of NPs can enable the self-assembly of novel cell-nanoparticle biomaterials with unique electron transport and catalytic properties.

Cardiovascular diseases remain the leading cause of mortality, necessitating advancements in in vitro cardiac tissue engineering platforms for improved disease modeling, drug screening, and regenerative therapies. The chief challenge to recapitulating the beating behavior of cardiomyocytes is creation of the circular stress profile experienced by hollow organs in the natural heart due to filling pressure and integrated strategies for intercellular communication to promote cell-to-cell connections. We present a platform featuring addressable arrays of nanogrooved polydimethylsiloxane (PDMS) diaphragms for cell alignment and circular mechanical stimulation, with embedded silver nanowires (AgNWs) for electrical cues, so that cardiomyocyte functionality can be assessed under these synergistic influences. Central to our innovation is a two-layer PDMS diaphragm design that electrically isolates the liquid metal (EGaIn) strain sensor in the bottom layer to enable detection and control of mechanical stimulation from conductive portions of embedded AgNWs in the top layer that supports cardiomyocyte culture and communication. In this manner, through localized detection and control of the circular mechanical stimulation, the essential role of multiaxial stretching on cardiomyocyte function is elucidated based on their contractility, sarcomere length, and connexin-43 expression. This in vitro platform can potentially transform cardiac tissue engineering, drug screening, and precision medicine approaches.

Cryopreservation and transplantation of ovaries are considered to be effective methods for preserving the fertility of female cancer patients. However, ice crystal and oxidative damage occur during the freeze-thaw cycle, significantly reducing the effectiveness of cryopreservation and limiting its clinical application. Thus, new technologies or agents must be explored to enhance ovarian cryopreservation. Recently, l-proline, a natural amino acid, has been proven to have good biocompatibility and can clear reactive oxygen species produced during cryopreservation. Whether l-proline can play a positive role in ovarian cryopreservation has not yet been explored. Here, the effect of l-proline on ovarian cryopreservation was investigated. The oxidative antioxidant system, mitochondrial function, and cell apoptosis and proliferation after thawing were systematically evaluated. Moreover, the ice crystal inhibition of l-proline was examined. Furthermore, the morphology and function of oocytes in ovaries, as well as the state of the ovaries after heterotopic renal capsule transplantation, were evaluated to validate the feasibility and reliability of this study. The above results confirm that l-proline can effectively inhibit ice crystal growth, reduce reactive oxygen species production, and enhance cryopreservation effects at the optimal concentration of 20 mM. Altogether, l-proline can significantly improve the cryopreservation effect of ovaries, which is expected to provide a new perspective for the cryopreservation of female fertility.

Accurate acetaminophen (APAP) determination using smartphone-based portable sensing hinges on developing sensing interfaces with effective catalytic performance and high electron transfer efficiency. Herein, we report that various Ni-based bimetallic-organic framework materials (MOFs) were synthesized through the hydrothermal method. These MOFs were incorporated with multiwalled carbon nanotubes (MWCNTs) during the synthesis of chitosan-cationic guar gum hydrogels (HG). The resulting composite conductive hydrogel features a distinctive three-dimensional network structure with a large specific surface area, enhancing APAP enrichment and electrocatalytic activity. Among them, CuNi-MOF-based chitosan-cationic guar gum conductive hydrogel (CHG/CuNi-MOF) has the most desirable capability as a signal amplifier. Under optimal conditions, the sensor constructed with the screen-printed electrode (SPE) using CHG/CuNi-MOF (CHG/CuNi-MOF/SPE) has a wide detection range (0.07-1500 μM), a low detection limit (0.023 μM), and a relatively high sensitivity (0.0450 μA·μM^-1·cm^-2) for the APAP determination. In addition, CHG/CuNi-MOF/SPE has good stability, repeatability and anti-interference properties, which make it possible to achieve selective determination of targets in complex analysis and ultimately obtain satisfactory recoveries (97.6-104.2%). This work successfully proves the feasibility of the application of MOFs-based conductive hydrogel in the electrochemical detection of phenolics in actual samples.

Inhaled therapy has become a crucial treatment option for respiratory diseases like asthma, cystic fibrosis, and chronic obstructive pulmonary disease (COPD), delivering drugs directly to bronchial and alveolar tissues. However, traditional static in vitro cell models, while valuable for studying pharmacokinetics (PK) and pharmacodynamics (PD), fall short in replicating the dynamic nature of physiological breathing. In this study, we present a breathing lung chip model that integrates a dynamic breathing mechanism with an air-liquid interface (ALI) culture environment to overcome these limitations. The platform replicates key aspects of lung physiology, including a functional airway interface, cyclic breathing motion, and medium circulation. Using the Calu-3 cell line to model airway epithelium, our experiments show that the incorporation of breathing motion significantly enhances the efficacy of inhaled drug delivery and cellular uptake, resulting in improved treatment outcomes compared to direct exposure of the drug. While further research is needed to explore its full potential, this platform holds promise for advancing inhaled drug screening and respiratory disease research.

The accumulation of senescent cells, a hallmark of aging and age-related diseases, is also considered as a side effect of anticancer therapies, promoting drug resistance and leading to treatment failure. The use of senolytics, selective inducers of cell death in senescent cells, is a promising pharmacological antiaging and anticancer approach. However, more studies are needed to overcome the limitations of first-generation senolytics by the design of targeted senolytics and nanosenolytics and the validation of their usefulness in biological systems. In the present study, we have designed a nanoplatform composed of iron oxide nanoparticles functionalized with an antibody against a cell surface marker of senescent cells (CD26), and loaded with the senolytic drug HSP90 inhibitor 17-DMAG (MNP@CD26@17D). We have documented its action against oxidative stress-induced senescent human fibroblasts, WI-38 and BJ cells, and anticancer drug-induced senescent cutaneous squamous cell carcinoma A431 cells, demonstrating for the first time that CD26 is a valid marker of senescence in cancer cells. A dual response to MNP@CD26@17D stimulation in senescent cells was revealed, namely, apoptosis-based early response (2 h treatment) and ferroptosis-based late response (24 h treatment). MNP@CD26@17D-mediated ferroptosis might be executed by ferritinophagy as judged by elevated levels of the ferritinophagy marker NCOA4 and a decreased pool of ferritin. As 24 h treatment with MNP@CD26@17D did not induce hemolysis in human erythrocytes in vitro, this newly designed nanoplatform could be considered as an optimal multifunctional tool to target and eliminate senescent cells of skin origin, overcoming their apoptosis resistance.

Small extracellular vesicles (sEVs) are promising nanocarriers for drug delivery to treat a wide range of diseases due to their natural origin and innate homing properties. However, suboptimal therapeutic effects, attributed to ineffective targeting, limited lysosomal escape, and insufficient delivery, remain challenges in effectively delivering therapeutic cargo. Despite advances in sEV-based drug delivery systems, conventional approaches need improvement to address low drug-loading efficiency and to develop surface functionalization techniques for precise targeting of cells of interest, all while preserving the membrane integrity of sEVs. We report an enhanced gene delivery system using multifunctional sEVs for highly efficient siRNA loading and delivery. The integration of chiral graphene quantum dots enhanced the loading capacity while preserving the structural integrity of the sEVs. Additionally, lysosomal escape is facilitated by functionalizing sEVs with pH-responsive peptides, fully harnessing the inherent homing effect of sEVs for targeted and precise delivery. These sEVs achieved a 1.74-fold increase in cytosolic cargo delivery compared to unmodified sEVs, resulting in substantial gene silencing of around 73%. Our approach has significant potential to advance sEV-based gene delivery in order to accelerate clinical progress.

Perianal fistulas (PAFs) are a severe complication of Crohn's disease that significantly impact patient prognosis and quality of life. While stem-cell-based strategies have been widely applied for PAF treatment, their efficacy remains limited. Our study introduces an injectable, temperature-controlled decellularized adipose tissue-alginate hydrogel loaded with dental pulp mesenchymal stem cells (DPMSCs) for in vivo fistula treatment. The experimental group demonstrated higher healing rates compared to surgical and DPMSCs groups, as evidenced by magnetic resonance imaging, multiplex immunohistochemical, and ELISA analyses. KEGG enrichment of differential genes suggested cellular senescence involvement in cell therapy efficacy, further confirmed by β-galactosidase staining and senescence markers (p21 and p53). Collectively, our research provides a novel therapy for PAFs and illuminates underlying mechanisms.

Chemotherapeutic drugs often fail to localize efficiently to tumors when administered intravenously, causing off-target effects. This study proposes an autologous erythrocyte (ER)-anchoring strategy to improve chemotherapy efficacy and reduce side effects. Utilizing a modified hemodialysis instrument, a closed-system drug-transfer device was developed for autologous ER procurement and immunogenicity mitigation. Doxorubicin (DOX) and indocyanine green (ICG) were encapsulated in autologous ERs and then modified with DSPE-PEG-FA. The final product, DOX-ICG@ER-D, was reintroduced into circulation to enhance chemotherapy. These obtained DOX-ICG@ER-D showed good stability, minimal cardiotoxicity, and extended circulation time. Compared to free DOX, DOX-ICG@ER-D had a higher accumulation of DOX in hepatocellular carcinoma and the release of DOX could be controlled by laser irradiation. Tumor-bearing rats treated by these DOX-ICG@ER-D demonstrated improved antitumor efficacy and reduced cardiotoxicity. Thus, this autologous ER-anchoring strategy offers a promising alternative to intravenous chemotherapy in the clinic.

Generation of in vitro tissue models with serially perfused hierarchical vasculature would allow greater control of fluid perfusion throughout the network and enable direct mechanistic investigation of vasculogenesis, angiogenesis, and vascular remodeling. In this work, we have developed a method to produce a closed, serially perfused, multiscale vessel network fully embedded within an acellular hydrogel, where flow through the capillary bed is required prior to fluid exit. We confirmed that the acellular and cellular gel-gel interface was functionally annealed without preventing or biasing cell migration and endothelial self-assembly. Multiscale connectivity of the vessel network was validated via high-resolution microscopy techniques to confirm anastomosis between self-assembled and patterned vessels. Lastly, using a simple acrylic cassette and fluorescently labeled microspheres, the multiscale network was demonstrated to be perfusable. Directed flow from inlet to outlet mandated flow through the capillary bed. This method for producing closed, multiscale vascular networks was developed with the intention of straightforward fabrication and engineering techniques so as to be a low barrier to entry for researchers who wish to investigate mechanistic questions in vascular biology. This ease of use offers a facile extension of these methods for incorporation into organoid culture, organ-on-a-chip (OOC) models, and bioprinted tissues.