Biointerphases最新文献

DNA nanostructures are promising materials for drug delivery due to their unique topology, shape, size control, biocompatibility, structural stability, and blood-brain-barrier penetration capability. However, their cellular permeability is hindered by strong electrostatic repulsion from negatively charged cellular membranes, posing a significant obstacle to the use of DNA nanostructures as a drug delivery vehicle. Recent experimental studies have shown enhanced cellular uptake for the conjugate binary mixtures of DNA Tetrahedron (TDN) with cationic lipid N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA) compared to TDN alone. However, the cationic DOTMA lipid binding mechanism with the TDN nucleotides is still elusive. Using fully atomistic MD simulations, we aim to understand the molecular interactions that drive the formation and stability of the TDN-DOTMA binary complexes in a physiological environment. Our results uncovered that lipid concentration plays a crucial role in the energetics of the TDN-DOTMA association. We also report that distinct time scales are associated with the self-assembly of cationic DOTMA lipids first, followed by the complexation of self-assembled DOTMA lipid clusters with the TDN nucleotides, where electrostatics, hydrophobicity, and hydrogen bonding are the key interactions that drive the formation and stability of these complexes. Our results provide molecular insights into TDN-DOTMA interactions, highlighting the lipid self-assembly dynamics, complex stability, and morphology, paving the way for the better rational design of cationic lipid-functionalized DNA nanostructures for efficient drug delivery and transfection.

Epithelial ovarian cancer is a gynecological disease in which transformed cells, upon dissemination into the peritoneum colonize locales such as omenta and form metastatic foci. Colonization is an emergent outcome of the interactions between the invading cancer cells and extracellular matrix (ECM) of the peritoneal serosa. Although ECM is known to be remodeled in cancer, the dynamics in ovarian cancer of a major class of ECM-remodeling factors: the proteoglycans remain understudied. Here, we focus on Decorin, a proteoglycan with binding activity to the principal stromal ECM protein Collagen I and investigate its regulation of ovarian cancer colonization. We observe that Decorin is depleted in cancer deposits within omenta of cancer patients. The spreading of suspended spheroids of the ovarian cancer line SK-OV-3 on engineered Collagen I scaffolds is impaired when the latter is polymerized in the presence of Decorin. Decorin-supplemented Collagen I shows poorer fibrillar organization, which has been associated with slower kinetics of cancer cell migration. To our surprise, Decorin was also found to be depleted in primary tumor cells as well as in ovarian cancer cell lines compared with their controls. Overexpression of wild type Decorin, but not its glycosaminoglycan (GAG)-removed mutant in cancer cells decreased mean spheroid size, invasion through Collagen I matrix, and migration on fibronectin matrix scaffolds. Our results suggest that downregulation of an extracellular inhibitor of colonization occurs both in the seed and soil components of the metastatic toolkit; in addition, the GAG chains of Decorin may be crucial to its carcinomatosis-inhibiting functions.

Copper intrauterine devices (Cu-IUDs) are widely used for long-term contraception; yet, the burst release of Cu2+ during early implantation often induces adverse uterine responses. In this study, a femtosecond laser texturing method was employed to construct a biomimetic microstructure (Cu#BM) inspired by Epipremnum aureum leaves. The engineered surface exhibited enhanced corrosion resistance and a moderated ion-release profile in simulated uterine fluid, effectively mitigating the initial burst of Cu2+. Electrochemical measurements, immersion tests, and cytocompatibility assays consistently confirmed the improved stability and biocompatibility of Cu#BM compared with unmodified Cu. These findings suggest that femtosecond laser-induced surface engineering provides a simple and effective strategy to suppress the early burst release of Cu2+, thereby offering translational potential to reduce clinical side effects associated with Cu-IUDs.

Indirect co-culture, wherein two distinct cell types are cultivated within the same medium without direct contact, remains a relatively underexplored approach in biomaterials science for simulating physiological cell-cell interactions on material surfaces in vitro. In this study, human mesenchymal stem cells (hMSCs) were cultured on two types of Ti6Al4V substrates (polished and sand-blasted/acid etched) in a co-culture system using conditioned osteogenic differentiation media (cOBM), enriched with soluble factors secreted by human osteoblasts (hOBs). The combined impact of surface microtopography of Ti6Al4V substrates and cOBM supplementation has resulted in the modulation of cell morphology, alkaline phosphatase (ALP) activity, and calcium phosphate mineralization. Enhanced mineralization (2.5-fold increase compared to baseline at day 21) was observed on Ti6Al4V substrates when hMSCs were cultured in the presence of cOBM. This was accompanied by a peak expression of the early osteogenic marker, ALP by day 14. The synergistic behavior of sandblasted and acid-etched substrates with soluble biochemical cues, derived from hOBs showcased their potential for augmenting osteogenic differentiation. The in vitro outcomes were validated in a rabbit model study, which clearly demonstrated better osseointegration of sand-blasted/acid etched implants over 12 weeks.

Peptides that selectively bind to inorganic surfaces play a crucial role in nanobiotechnology, biomaterials, and biosensing applications. While phage display has been the predominant method for identifying such peptides, its selection process is influenced by propagation biases and experimental constraints, which may lead to the exclusion of peptides with superior binding affinity. In this study, we implement a molecular dynamics simulation to systematically assess the binding affinity of 46 solid-binding peptides, which were manually curated from literature with previously identified affinities to various surfaces to Au(111). We perform a comprehensive analysis, including interaction energy calculations, molecular mechanics/Poisson-Boltzmann-surface area, root mean square deviation, and distance of each residue with Au(111) to elucidate the molecular determinants of solid-binding peptide-Au(111) interactions. Our results reveal that while phage display-derived peptides exhibit affinity, several peptides not previously categorized as Au(111) binding show stronger affinity than the experimentally identified Au-binding sequences. We propose the term "promiscuous binding peptides" to describe these sequences, which demonstrate high affinity for surfaces beyond their original selection targets. Our findings highlight the limitations of experimental selection techniques and emphasize the potential of computational screening in identifying higher-affinity peptides toward the target metal interfaces. This study establishes a foundation for advancing the rational design of functional solid-binding peptides.

Biofilm-biomaterial interfaces have an important role in biofilm development and pose a critical challenge in healthcare, contributing to device failures and chronic infections that affect patient outcomes and healthcare economics. This review explores the complex dynamics of these interfaces, from initial protein adsorption through mature biofilm development, highlighting how bacteria and materials are involved in bidirectional interactions that determine both infection progression and material degradation. It also examines different advanced analytical methods for characterizing these dynamic biofilm-biomaterial interactions, with particular emphasis on the recent developments in electrochemical techniques (ion-selective electrodes, electrochemical impedance spectroscopy, and scanning electrochemical microscopy) that enable real-time monitoring of critical parameters such as pH, oxygen gradients, and metabolic activities, providing unique insights into biofilm heterogeneity and localized chemical changes. In addition, the review explores future developments in sensor technology and standardized protocols needed to accelerate biomaterial innovation, potentially transforming our approach to implant-associated infections through responsive surfaces that adapt to microbial challenges.

For this study, zeolite powder served as a substrate for inoculating Metarhizium robertsii to demonstrate the biocompatibility between the entomopathogenic fungus and the zeolite mineral, as the initial step in developing a biological control agent. Our fungal strains were isolated from corpses of spittlebugs (Aeneolamia albofasciata, Hemiptera: Cercopidae) and were identified as M. robertsii based on sequencing of the Internal Transcribed Spacer regions ITS1 and ITS2. Zeolite was characterized using x-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive spectroscopy (EDS). XRD and EDS results indicate that zeolite consists of a mixture of Heulandite and Clinoptilolite. EDS analysis shows that oxygen, silicon, and aluminum are the primary chemical components of the zeolite powder, with calcium, magnesium, iron, sodium, and potassium present in smaller amounts. After five days of inoculation, SEM images reveal M. robertsii conidia on the porous surface of zeolite particles, along with hyphal formation. These findings suggest the potential for maintaining M. robertsii spores and mycelium alive within a zeolite substrate under laboratory conditions.

Mass spectrometry (MS) often requires vacuum conditions, which, while beneficial for analysis, can unpredictably alter sensitive samples. This study investigates the impact of prolonged vacuum exposure on the consistency and reliability of MS detection of thin films of acetaminophen using secondary ion mass spectrometry (SIMS). Under vacuum at room temperature, the mass spectrometry signal intensity decreased by approximately 81.5% over the duration of the experiment (42 h). Optical microscopy revealed that this decrease coincided with sublimation-induced sample loss of the acetaminophen. As a result, acetaminophen coverage across the substrate became heterogeneous, leading to increased relative standard deviation (RSD) in the SIMS signal over time. In contrast, under cryogenic conditions, neither signal degradation nor an increase in RSD was observed. Additionally, a comparison with atmospheric pressure mass spectrometry revealed that, in the absence of vacuum, signal intensity remained more stable over time. These findings highlight the potential drawbacks of vacuum exposure for volatile standards and emphasize the importance of testing vacuum effects prior to analysis. If vacuum is necessary, cryogenic conditions should be considered to mitigate sample degradation. While these effects were observed for a mass spectrometry technique, they are also applicable to any type of vacuum-based methodology where the samples might be prone to sublimation.

The lack of cementum in peri-implant tissues leads to a deficiency in anchorage points for gingival collagen fibers. This arrangement is linked to reduced protective capabilities compared to teeth. Therefore, there is a pressing need to develop surfaces that optimize the interaction between soft tissue and implants. 3D-printed titanium disks (Ti3DP), machined disks (TiMC), and glass coverslips (GS) were seeded with human gingival fibroblasts. These specimens underwent mechanical characterization via roughness and wettability assays. Biological characterization included assessments of cellular viability (live/dead), adhesion and spreading (F-actin), cell count (DAPI), cellular metabolism (Alamar blue), adhesive strength, and soluble collagen and total protein quantification up to 14 days. Data analysis employed Student's t-test and ANOVA post-hoc Tukey test (α = 0.05). The group TiMC exhibited higher hydrophilicity and lower roughness compared to Ti3DP. All groups demonstrated cellular viability throughout the study period. Adhesive strength did not significantly differ among groups; however, cell count was higher in TiMC and GS after one day of cell seeding in comparison to Ti3DP. Morphologically, GS and TiMC displayed more fusiform cells with a uniform distribution, while Ti3DP showed smaller, irregular cells with multiple lamellipodia and filopodia. Additionally, statistically superior collagen and total protein deposition was observed in Ti3DP (p < 0.01). The 3D-printed titanium surface allowed human gingival fibroblasts to adhere to it, leading to a 3D cytoskeleton morphology that culminated in increased collagen expression. Therefore, these 3D-printed devices present a promising avenue for producing transmucosal components due to their increase in collagen production.

Poly(ɛ-caprolactone) (PCL) remains widely studied in biomaterials science and biomedical engineering due to its versatility and applicability in regenerating a range of tissues including bone, cartilage, neural, and cardiovascular. Due to the hydrophobicity of PCL, most PCL based systems for tissue regeneration require a surface modification process to enhance its in vitro and in vivo compatibility. This Perspective aims to provide an overview of recent strategies used to modify 2D films and 3D scaffolds and the associated methods used to characterize these surfaces. The scope is restricted to physical and chemical postmodification methods, excluding blends and composites, to better isolate the effects of surface chemistry. By analyzing the latest studies (published in 2022-2024), we classified the most commonly employed surface modification techniques, and we identified that the surface evaluation of tailored PCL remains a critical challenge in terms of both chemical and morphological characterization as well as the stability of the introduced surface layer/coating. This status of recent literature highlights current excellent practices and characterization methodologies and suggests approaches for refining surface engineering methods of PCL-based biomaterials in the future.