ACS Biomaterials Science & Engineering最新文献

Bacterial infections have been demonstrated to cause the premature failure of implants. A reliable strategy for preserving biocompatibility is to physically modify the implant surface, without using chemicals, to prevent bacterial adhesion. This study employed femtosecond laser processing to generate various laser-induced periodic surface structures on Ti substrates. The antibacterial properties and osteoblast adhesion characteristics of these surfaces were investigated. Gene expression profiles and transcriptomic data were compared before and after laser treatment, and high-throughput analysis was conducted to evaluate the antibacterial performance related to different surface modifications. A small data set of Ti surface scanning electron microscopy images was compiled, and a deep learning model was trained using transfer learning to facilitate surface recognition and classification. The results demonstrated that femtosecond laser treatment disrupted bacterial adhesion and the expression of adhesion-related genes on the Ti surface, with the laser-treated samples at 5.6 W and 500 mm/s exhibiting an antibacterial efficacy exceeding 60%. In addition, the optimized deep learning model, ResNet50-TL, accurately identified and classified the structures of Ti surfaces post-treatment.

Collagen-hyaluronic acid (Col-HA) hydrogels are widely studied as biomimetic materials that recapitulate the environmental physical and mechanical properties crucial for understanding the cell behavior during cancer invasion and progression. Our research focused on Col-HA hydrogels as an environment to study the invasion of bladder cancer cells through the bladder wall. The bladder is a heterogeneous structure composed of three main layers: urothelium (the softest), lamina propria (the stiffest), and the muscle outer layer, with elastic properties lying between the two. Thus, the bladder cancer cells migrate through the mechanically distinct environments. We investigated the impact of Col-HA hydrogel microstructure and rheology on migrating bladder cancer T24 cells from the cancer spheroid surface to the surrounding environment formed from various collagen I and HA concentrations and chemical structures. The designed hydrogels showed variability in network density and rheological properties. The migration of bladder cancer cells was inhibited inside hydrogels of ∼1 kPa storage modulus. The correlation analysis showed that collagen concentration primarily defined the rheological properties of Col-HA hydrogels, but hydrogels can soften or stiffen depending on the type of HA used. Within soft Col-HA hydrogels, cells freely invade the surrounding environment, while its stiffening impedes cell movement and almost inhibits cell migration. Only individual, probably leading, cells are observed at the spheroid edges initiating the invasion. Our findings showed that the rheological properties of the hydrogels dominate in regulating cancer cell migration, providing a platform to study how bladder cancer cells migrate through the heterogeneous structure of the bladder wall.

Hybrid nanoparticles (HNPs) offer integrated advantages in comparison to the singular-component systems of nanomaterials. This study reports a simple, one-pot green synthesis of hydrophilic selenium-iron-sulfur hybrid nanoparticles (Se-S-Fe HNPs) using an Alstonia scholaris extract. The size and surface charge of the Se-S-Fe HNPs, characterized by advanced material characterization techniques, significantly influenced their antimicrobial activity against Escherichia coli and Bacillus megaterium. However, mechanistic studies uncovered distinct modes of action against these bacterial species. Transcriptomic analysis revealed Se-S-Fe HNPs disrupted protein synthesis in E. coli and elevated the expression of outer membrane proteins OmpA and OmpC. In B. megaterium, the HNPs induced hyperosmotic shock and broad metabolic changes, impacting amino acid biosynthesis and protein localization. This work introduces a facile and environmentally friendly method for producing effective antimicrobial nanomaterials with distinct mechanisms of action depending on bacterial species.

Extracellular vesicles (EVs) have garnered significant attention in the biomedical field due to their potential applications. However, their small size and high heterogeneity pose challenges for precise manipulation. Recent advancements have focused on the assembly of DNA nanostructures on EV membranes, leveraging the precise programmability and unique base pairing of DNA to enable the customized modification and manipulation of EVs. This perspective examines the design and characterization of DNA nanostructure-based assemblies on EV membranes, with an emphasis on enhancing efficiency in EV separation, cancer diagnosis, and therapy. For EV separation, DNA materials facilitate highly selective separation through specific binding to membrane molecular markers by passing the need for sophisticated instrumentation and complex procedures. In cancer diagnosis, DNA nanostructures on EVs act as efficient recognition and sensing modules for cancer-associated biomarkers, offering robust tools for accurate cancer detection. In drug delivery, these assemblies enhance the targeting efficiency and drug loading stability of EVs, ensuring a precise delivery and efficient release at lesion sites. Furthermore, this review discusses the current challenges and future development prospects in this field, aiming to inspire new ideas and methodologies for EV-based biomedical research.

Developing bone replacement scaffolds has been a driving ambition of regenerative medicine. Although great progress has been achieved for small scaffolds, the real clinical need is for large scaffolds >5 mm. Oxygenating these scaffolds is challenging, as slow diffusion rates lead to necrotic regions in the scaffold core. In this work, we modulate in vitro oxygen concentration in a scaffold in a flow chamber using an external perfusion pump while imaging oxygen concentrations below the scaffolds. With no external flow, yeast cells growing in the scaffold deplete oxygen, especially from the center, with concentrations reaching a steady state consistent with reaction-diffusion models. The oxygen is restored via pumping fresh medium through the scaffold. The oxygen profiles are highly reproducible from cycle to cycle. This lays the groundwork for future in vivo oxygen imaging studies using localized light sources and external perfusion pumps for modulation.

Methotrexate (MTX) is one of the mainstays in the treatment of psoriasis and psoriatic arthritis. However, it is mainly administered orally or by subcutaneous injection, which is not so satisfactory with many side effects. While orally administered MTX may cause gastrointestinal side effects, subcutaneous injection is often painful and may affect patient compliance. To address these limitations, we investigated the minimally invasive transdermal drug delivery strategy, a piezoelectric-driven microneedle array (PDMA) that can efficiently overcome the thickened epidermis and controlled delivery of MTX. PDMA was prepared from piezoelectric ceramic disks and a 3D-printed microneedle array patch. The finite element model was established to validate the ultrasound field generated by PDMA and analyze the relationship between the frequency and amplitude of PDMA penetrating the skin. PDMA demonstrated a satisfactory enhancement of drug permeation and achieved greater depth of delivery of MTX, enhanced 9 times compared with untreated skin in the in vitro study. The in vivo study demonstrates that PDMA-mediated delivery of MTX significantly enhances therapeutic outcomes in alleviating psoriasis symptoms, outperforming oral administration while requiring only 50% of the conventional oral dosage. Therefore, PDMA could be a promising approach for effective and controlled transdermal drug delivery methods of MTX as a potential enhanced treatment for psoriasis.

Microalgae robots are an emerging biohybrid microrobot that combines the biological properties of microalgae with microrobot technology and shows a wide range of applications in the medical field. In recent years, it has been found that microalgae are ideal biodriven carriers as they have good binding sites and unique properties such as motility, light responsiveness, and oxygen production. The natural substances inside microalgae also have certain medical value and can act synergistically with the exogenous drugs carried. This study provides an in-depth summary of the progress of research and application of microalgae robots in biomedicine over the past 3 years, with a view of providing new ideas for the fabrication and medical application of microalgae robots. This review first introduces the structure and properties of microalgae, which is the basis for the design of microalgae robots; second, it summarizes the formation and movement of microalgae robots, which are formed by functionalizing the surface of microalgae to form microalgae robots with various functions and driven to move in a directional manner by their own targeting ability and external means; the last and most important is it introduces the current research status of microalgae robot applications in drug delivery, targeted treatment of tumors and gastrointestinal inflammation, medical imaging, tissue regeneration, and other fields, as well as their advantages in terms of environmental friendliness, and the future prospects of microalgae robots in the field of biomedicine are also demonstrated.

The rapid emergence of antimicrobial resistant Gram-negative bacteria compromises current antibiotic efficacy, including the last-resort antibiotic polymyxins, emphasizing the urgent need for novel therapeutic strategies. Nanoscale-based antimicrobials exhibit potential as an alternative treatment strategy. In this study, four furoxan-based nitric oxide (NO)-releasing nanoparticles (NPs) were prepared and their antimicrobial efficacy was tested against different Gram-negative bacteria, including: Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli via minimum inhibitory testing, where NPs exhibited selective activity against lipopolysaccharide (LPS)-deficient A. baumannii strains and LPS-truncated strains tested. Advanced microscopic techniques and mechanistic investigations using model membranes mimicking the LPS-deficient A. baumannii membrane and LPS-containing membrane, via neutron reflectometry and small-angle neutron scattering, indicated that the NPs specifically destabilize the LPS-deficient A. baumannii membrane, leading to the release of cellular content. This work provides mechanistic insight into the selective activity of the NPs against LPS-deficient A. baumannii and their lack of efficacy in strains with LPS, highlighting membrane-level determinants that may inform future antimicrobials development.

Enhancing flap survival is essential in flap surgery. Cell-free fat extract (Ceffe), a "natural cocktail" of bioactive compounds derived from adipocytes, has demonstrated the potential to improve flap viability. However, direct local injection of Ceffe is limited by its quick leakage and short duration of effectiveness. To address these limitations, this study encapsulated Ceffe in a gelatin methacrylate (GelMA) hydrogel to develop a more stable releasing system. The role of Ceffe in promoting angiogenesis and facilitating flap repair was evaluated by using CCK-8 assays, scratch assays, and tube formation assays. Its antioxidative stress effect was first assessed using flow cytometry and further validated through subsequent experiments employing immunofluorescence and PCR. Scanning electron microscopy (SEM) confirmed that Ceffe@GelMA retained a porous structure, while rheological testing demonstrated its injectability. Drug release assays indicated that GelMA, containing a high concentration of Ceffe, was capable of sustained Ceffe release beneath the flap, thereby promoting flap repair. The biocompatibility of GelMA was assessed using Phalloidin staining, live-dead staining, CCK-8 assays, hemolysis tests, and subcutaneous degradation assay, all of which demonstrated favorable biocompatibility. In a murine random skin flap model, temperature measurements of the flap suggested that Ceffe@GelMA exhibited significant pro-repair activity. Histological analysis through HE and Masson's trichrome staining revealed the presence of abundant neovessels. Immunofluorescence analysis of endothelial marker CD31, vascular endothelial growth factor (VEGF), and smooth muscle actin (α-SMA) further supported that the Ceffe@GelMA treatment group exhibited enhanced pro-angiogenic potential. This study provides substantial evidence supporting Ceffe's therapeutic efficacy in flap necrosis prevention and establishes a Ceffe-incorporated hydrogel system, representing a significant advancement in clinical treatment strategies.

Photothermal therapy (PTT) faces critical limitations due to tumor hypoxia, intrinsic resistance, and metastasis. To address these challenges, we developed a trimodal nanoplatform (R-R/PB@PPy NEs) by synergizing Prussian blue (PB)/polypyrrole (PPy) nanozymes, tumor suppressor reactivation, and immune modulation. Through Fe³⁺ -mediated one-step oxidative polymerization, PB and PPy were integrated into a hybrid nanozyme and further functionalized with rosiglitazone (PPAR-γ agonist) and rutin (tumor-targeting ligand). The R-R/PB@PPy NEs achieved a photothermal conversion efficiency of 31.6% and catalase/superoxide dismutase-like enzymatic activity, persistently alleviating hypoxia via oxygen generation. Simultaneously, AKT/mTOR-mediated PTEN upregulation suppressed tumor proliferation and metastasis. Rutin-mediated tumor targeting enhanced drug accumulation at tumor sites, which synergistically amplified immunogenic cell death induction, promoting dendritic cell maturation and cytotoxic T-cell infiltration. In vivo, this platform completely inhibited 4T1 tumor growth, eradicated lung metastasis, and prevented recurrence (0% at 56 days) with an 80% long-term survival rate and no systemic toxicity. By unifying catalytic nanozyme design, PTEN-driven sensitization, and immune activation, this study establishes an interdisciplinary strategy to overcome resistance in PTT, offering a translatable approach for precision cancer therapy through tumor microenvironment modulation.