ACS Biomaterials Science & Engineering最新文献

Cell spheroids are three-dimensional spherical aggregates of cells that show advantages for mimicking living tissues, owing to their structure. However, issues such as cell necrosis often result in limited cell survival and functional expression. The introduction of biocompatible functional material spacers into cell spheroids can not only improve cell survival by facilitating free diffusion of oxygen, nutrients, and waste products but also enables the incorporation of novel functions into the cell spheroids. In this study, we focused on cholesterol-modified pullulan (CHP) nanogels, which exhibit protein complexation and controlled release properties. The microfiber spheroid spacers were produced by cross-linking the CHP nanogels with poly(ethylene glycol) (PEG). Using freeze–thaw cycles and ultrasonic irradiation, we successfully developed a simple and high-yielding method for microfiber fabrication. The microfibers retained the protein complexation and controlled the release properties of the CHP nanogels. Furthermore, fluorescence-labeled microfibers were integrated uniformly with mouse myoblast cells (C2C12) to give hybrid cell spheroids. The hybrid cell spheroids were scaled up to millimeter size, demonstrating that the cells maintained a high viability. The hybrid cell spheroids are expected to support not only the construction of organoids but also advances in cell therapy and the development of new treatment modalities.

The bone marrow niche is a specialized microenvironment sustaining a hematopoietic stem cell (HSC) pool and regulating the production of mature blood cells. Its exact composition and mechanisms remain incompletely defined, mainly due to the lack of in vitro models that accurately reproduce its physiological three-dimensional (3D) architecture and cellular crosstalk. Two-dimensional cultures fail to sustain HSC quiescence and stemness, while advanced 3D systems can reproduce key structural and mechanism cues of the niche. In this review, we first describe physiological cellular, stromal, and matrix components of the bone marrow niche, highlighting their coordinated regulation of HSC maintenance, proliferation, and mobilization. We then critically examine current approaches for 3D in vitro bone marrow models, including scaffold-based methods, decellularized models, spheroid and organoid systems, 3D bioprinting applications, and organ-on-chip technologies, discussing their advances, limitations, and potential disease modeling in this field. Finally, we outline how these technologies could deepen our understanding of hematopoiesis mechanisms, clonal evolution, and niche-mediated drug resistance. We also highlight the pros and cons of each methodology and future directions toward standardized protocols, integrating tissue components, and the use of human cells to enhance reproducibility and clinical relevance. Advances like bone marrow-on-a-chip, computational models, and patient-specific systems will help bridge the gap between in vitro and in vivo studies, enabling drug testing, stem cell expansion, and gene editing strategies, including chimeric antigen receptor expression. Bone marrow models have evolved from simple 2D cultures to advanced 3D and organ-on-a-chip systems, significantly improving our understanding of hematopoiesis and accelerating new therapies.

Matrix metalloproteinases (MMPs) are central to extracellular matrix remodeling, and their upregulation is involved in numerous pathologies such as wound chronicity, carcinomas, or osteoarthritis. Sensing and monitoring MMP activity or exploiting their hydrolytic action as a trigger for targeted drug delivery represents promising avenues for innovative biomedical applications. Herein, we present a novel methodology to identify MMP-13-cleavable peptides that are optimized for both affinity and selectivity. To this aim, we developed a software named “CleavInsight” to generate a library of optimized peptide substrates considering complex biological environments alongside a “Competitive Substrate Fluorescence Assay” (CSFA). CSFA is a time-saving enzymatic assay that determines the affinity and selectivity of the synthesized peptides. We applied our methodology to osteoarthritic synovial fluid as a representative biological medium. The 24-candidate peptide sequences generated by the software were synthesized and tested in the CSFA with MMP-13. From this initial set, IC₅₀ values were calculated for the 8 peptides with the highest affinity, and the peptides were also screened for selectivity against MMP-9. The combination of CleavInsight software with the time-efficient CSFA constitutes a reliable toolkit for developing protease-responsive systems.

Mitochondria are essential organelles that govern energy metabolism, redox balance, and cell survival; their dysfunction is implicated in a wide range of pathologies, including neurodegenerative disorders, cardiovascular diseases, metabolic syndromes, and cancer. Despite their significance as therapeutic targets, the unique structural and electrochemical properties of mitochondria, particularly the impermeable inner mitochondrial membrane and high membrane potential pose major challenges for the targeted delivery of therapeutic agents. Recent advances in biomaterials have spotlighted peptide–polymer conjugates as versatile platforms, capable of navigating intracellular barriers and achieving precise mitochondrial localization. These hybrid systems combine the physicochemical tunability of polymers with the biofunctionality of peptides, enhancing cellular uptake, endosomal escape, and suborganelle trafficking. The incorporation of stimuli-responsive elements further enables spatiotemporal control of cargo release in response to intracellular cues such as pH shifts, thermal fluctuations, redox gradients, or enzymatic activity. Such systems are especially promising for mitochondrial gene and protein delivery, offering improved selectivity, reduced systemic toxicity, and the potential to restore mitochondrial function under pathological conditions. This review showcases advanced strategies in stimuli-responsive peptide–polymer systems for mitochondria-targeted delivery, highlighting how their smart, responsive functions enable precise, controllable therapeutic interventions and drive the development of next-generation, transformative biomaterials in precision nanomedicine.

Bioactive glass (BG) has emerged as a promising material in bone tissue engineering due to its unique ability to actively participate in the healing process. The present review introduces human natural bone and its properties, and the challenges posed in artificial bone material development. While much of the existing literature emphasizes its structural and compositional design, this review offers a novel perspective by focusing exclusively on the biological properties of BG that drive tissue regeneration. Key mechanisms, including osteoconduction, osteoinduction, angiogenesis, antibacterial activity, and immunomodulation, are critically examined to highlight how BG influences cellular behavior and the healing microenvironment. The review further presents recent in vitro and in vivo findings, compares the biological efficacy of different glass compositions, and discusses current clinical applications. By concentrating on the biological interface rather than fabrication strategies, this work provides an updated and focused framework for understanding the regenerative potential of BG and identifies future directions for enhancing its therapeutic performance. However, challenges such as controlling ion release kinetics, improving mechanical reliability and porosity balance, aligning degradation rates with tissue healing, ensuring predictable in vivo performance across diverse patient conditions, and overcoming barriers to large-scale clinical translation remain to be addressed. Addressing these limitations will be critical to fully realize the clinical potential of BG in bone regeneration.

We report a glioblastoma (GBM) in vitro model that combines an extracellular matrix (ECM)-mimicking hydrogel, hyaluronan (HA), GBM spheroids, and a blood-brain barrier (BBB) component. The model was designed to study the impact of the HA’s chain size (i.e., molecular weight, Mw) on cancer cell migration and on the permeability of the BBB. U-87 spheroids were encapsulated in alginate (Alg) hydrogels previously loaded with HA of different Mw, i.e., 5 kDa, 700 kDa, and 1.5 MDa, mimicking the tumor microenvironment (TME) of GBM. The results indicate that shorter HA molecules (i.e., 5 kDa) enhance the invasion of U-87 cells, as observed by time-lapse microscopy. Moreover, this increased cellular motility is accompanied by overexpression of cortactin by the U-87 cells confirming an increased cancer invasive character. In contrast, U-87 spheroids encapsulated in hydrogels that presented HA of higher Mw, i.e., 700 kDa and 1.5 MDa, presented reduced motility, being consistent with a limited cancer growth. Furthermore, dextran-based permeability measurements showed that the presence of HA of low Mw (i.e., 5 kDa) led to increased permeability of the BBB component, a feature that is characteristic of the blood-brain tumor barrier (BBTB). In summary, the developed 3D in vitro GBM model effectively recapitulates key features of the TME, highlighting the impact of the HA size on cancer cell invasion and BBB/BBTB permeability.

Viral infections of the respiratory tract, including those caused by respiratory syncytial virus, influenza, and coronaviruses, constitute a significant global public health burden. Central to the pathogenesis of these infections are the interactions between viruses and host mucosal barriers, particularly the complex glycoproteins known as mucins that are the primary constituents of mucus. Mucins function not only as physical barriers but also as immune modulators, with their glycan chains playing critical roles in viral recognition and binding processes. These viral-mucin interactions determine host specificity, influence transmission dynamics, and regulate immune responses. Conversely, viruses can alter mucus composition and compromise mucociliary clearance mechanisms. This review first examines the structural and functional properties of mucins, followed by a comprehensive analysis of the complex interactions between respiratory viral surface proteins and mucins, including virus-induced perturbations to airway mucus secretion. We summarize current knowledge of viral-mucin interactions to provide insights into the potential development of mucin-mimetic polymers for targeted viral engagement, with applications ranging from viral detection to infection inhibition. Additionally, we discuss biophysical methodologies for investigating interactions between viruses and glycans.

The development of core–shell nanostructures using heterogeneous materials in an ordered configuration enhances both antibacterial and electrochemical properties as a result of the synergistic effect of combined materials. In this study, we present a novel biocomposite core–shell nanostructure comprising Fe₂O₃ and xanthan gum (XG) for the electrochemical detection of Rhodamine B (RhB), a commonly used food dye and additive. The composite was synthesized through a simple and efficient method, involving the surface etching of Fe₂O₃ to promote strong interactions with XG. Transmission electron microscopy (TEM) confirmed the formation of the core–shell structure of nanocubes with a layer of ∼17 nm thickness. Electrochemical investigations revealed that Fe₂O₃@XG exhibits excellent electrocatalytic activity toward RhB, facilitated by intermolecular hydrogen bonding and electrostatic interactions. The sensor demonstrated a wide linear detection range from 50 nM to 400 μM, with a limit of detection (LOD) of 12.06 nM and a limit of quantification (LOQ) of 40.21 nM. Additionally, the composite displayed strong anti-interference characteristics, along with good reproducibility and stability. Real sample analysis showed high recovery percentage on spiking tomato sauce and chili powder, confirming its practical applicability. Beyond sensing capabilities, the composite also demonstrated potent antibacterial activity against Klebsiella pneumoniae and Pseudomonas aeruginosa, with inhibition zones measuring 17 ± 1.5 and 13 ± 2.5 mm, respectively. Free radical scavenging ability was confirmed via the DPPH assay, and hemolysis studies indicated excellent biocompatibility with a lysis rate of just 1.48%. Overall, the synthesized Fe₂O₃@XG core–shell biocomposite holds strong promise for designing devices for RhB detection, contributing to food safety monitoring and offering potential in biomedical applications.

Contrast-enhanced magnetic resonance imaging (CE-MRI) plays a pivotal role in the entire process of brain tumor diagnosis. However, safety concerns and the short imaging time window associated with clinical gadolinium (Gd)-based contrast agents limit the application of CE-MRI in brain tumors. In this study, a small-molecule manganese (Mn) chelate, Mn-PhDTA, was synthesized for long-term CE-MRI of brain tumors. Mn-PhDTA can be easily prepared through three-step reactions with an overall yield of 44% and suitable for gram-scale production. The benzene ring of Mn-PhDTA accelerates the bind to proteins, with longitudinal relaxivity increased by 1.88-fold to 5.14 mM^–1 s^–1 after binding at 3 T magnetic fields. After intravenous injection, Mn-PhDTA-enhanced CE-MRI significantly improved the contrast-to-noise ratios of gliomas. Furthermore, the enhancement persisted for 72 h, which is tens of times longer than that of clinical Gd-DTPA. Mn-PhDTA offers a promising alternative to Gd-based agents for the early detection of brain tumors.