ACS Biomaterials Science & Engineering最新文献

Spinal cord injury (SCI) poses a serious threat to human health. Addressing this condition presents major challenges, primarily in reducing neurotoxicity and promoting nerve regeneration. Here, we developed an innovative three-dimensional (3D) cellulose scaffold with hierarchically ordered multiscale channels, specifically designed to facilitate spinal cord repair. This bioinspired architecture is crucial, as it not only provides a physical guide for axonal growth but also supports cellular adhesion, proliferation, and differentiation. We identified that the scaffold’s regenerative efficacy is critically dependent on its filling degree within the lesion cavity, a finding that underscores the pivotal role of precise structural modulation in achieving functional recovery. Beyond providing structural support, this scaffold actively interacts with the hostile injury milieu. It positively regulates the post-SCI immune microenvironment by modulating inflammatory responses, which in turn enhances robust cellular infiltration, facilitates directional axonal growth, and encourages neuronal differentiation. We conclusively demonstrated its significant therapeutic potential for spinal cord regeneration in a mouse model of spinal cord injury, observing marked functional improvements and histological evidence of repair. The core innovation of this 3D platform lies in its versatility; by systematically adjusting scaffold structural parameters such as channel size and porosity, we can strategically optimize the injury-site microenvironment. 3D scaffolds with an 80% filling degree exhibit favorable structure and excellent regulatory properties, effectively facilitating the repair of SCI. This tunable system offers a promising and versatile solution for spinal cord repair, effectively bridging a critical gap in current treatments and paving the way for new regenerative therapeutic strategies.

Targeted delivery of chemotherapeutic agents can reduce systemic toxicity and enhance therapeutic outcomes by increasing the level of drug accumulation at tumor sites. In this study, we developed lipid-based cubosomal nanocarriers with an optimal size of 157 ± 20 nm for effective tumor penetration. This work represents the first demonstration of actively targeting cubosomes to epidermal growth factor receptors (EGFR) using a short peptide ligand. The peptide-functionalized cubosomes exhibited selective uptake of up to 75% in EGFR-overexpressing MDA-MB-468 breast cancer cells while showing minimal uptake (9%) in EGFR-negative HEK-293 cells. Paclitaxel-loaded targeted cubosomes significantly reduced MDA-MB-468 cell viability (47% survival at 60 μg/mL after 24 h) with negligible cytotoxicity in HEK-293 cells (87% survival). In 3D spheroid models, the survivability further decreased to 13% in MDA-MB-468 spheroids after 48 h, whereas HEK-293 spheroids remained largely unaffected. In vivo, targeted treatment suppressed tumor progression, yielding a mean tumor volume of 330 mm³, compared to 675 mm³ and 770 mm³ in untargeted and control groups, respectively, without observable liver or kidney toxicity. These results highlight the therapeutic potential of peptide-tagged cubosomes for the selective treatment of EGFR-expressing cancers.

Subclinical leaflet thrombosis is a major cause of failure in both surgical and transcatheter bioprosthetic heart valves. Thromboresistance is a basic prerequisite for a cardiovascular biomaterial. In this study, bovine pericardium (BP) was decellularized and processed (DCL-BP) with 0.2% glutaraldehyde (GA) and covalently conjugated with amino acid derivatives. Hexylamides of L-Glutamic acid (Glutamyl dihexylamide-GHA), L-Lysine (Lysinyl hexylamide─LHA), and the propargyl derivative of L-Lysine (Lysinyl propargyl amide─K1 alk) were investigated. These modifications of BP generate three different scaffolds (DCL-GHA BP, DCL-LHA BP, and DCL-K1 alk BP) of varying surface energies and hydrophilic/phobic properties. The surface modifications altered the water contact angles of glutaraldehyde-processed pericardium from 59.25° to 67.74° in DCL-GHA BP and 79.98° in DCL-LHA BP, while DCL-K1 alk BP became highly hydrophilic such that the measurement of static angle was not feasible. Successful conjugations were confirmed by quenching of acid fuchsin color reaction and confocal Raman chemical mapping. The materials were found to be non-hemolytic and greatly reduced the overall protein adsorption and platelet adhesion, thus markedly improving the surface thromboresistance in vitro as observed by the whole blood clotting assay. The results of the ex vivo study in the sheep model correlated well with the in vitro data, where a marked reduction in protein adsorption from whole blood and platelet adhesion/thrombus deposition was observed, in comparison with the thrombogenic control. There was no activation of coagulation or complement system by any of the three test materials, making them non-thromboinflammatory and suitable candidate materials for use as a bioprosthetic heart valve leaflet.

The present study introduces an injectable oxidized alginate-gelatin hydrogel system for cartilage tissue engineering, employing a combination of covalent and noncovalent cross-linking mechanisms. Specifically, the network is formed through Schiff’s Base reactions alongside enzymatic and ionic cross-linking. The hydrogels were investigated regarding their mechanical properties, swelling and degradation behavior, injectability, and cytocompatibility. The results indicated tailorable mechanical properties with an effective modulus ranging from 12 to 20 kPa, depending on the enzymatic cross-linker concentration, while demonstrating suitable injectability required for clinical applications with injection forces in the range of 3–5 N. Moreover, the syringe-mixing approach of in situ cross-linked hydrogels showed favorable cell–material interactions with chondrogenic ATDC5 cells.

The combination of membranes with coacervates has been regarded as an effective approach to stabilize coacervates and modify their surface properties. Here, we achieved the construction of a functional coacervate system by localizing nanovesicles assembled by elastin-like peptide-block-collagen-like peptides (ELP-CLPs) on the surface of polyelectrolyte coacervates. The formation of the ELP-CLP coating was driven by electrostatic interactions between negatively charged ELP-CLP vesicles and positively charged coacervates. Altering the surface charge of ELP-CLP vesicles or coacervates disrupted the formation of coatings, and the formulation parameters, such as different mixing protocols and the order of adding the components, could be used to control the coating process. The ELP-CLP vesicle coating successfully functionalized the coacervates and presented the ability to control the diffusion of molecules based on their different molecular weights. Our results demonstrated approaches to control the coating process and coating functionality of ELP-CLP vesicle coatings and highlighted their potential application as a novel surface modification to provide selective permeability to current coacervate systems.

Graphene-based quantum dots (GBQDs) are ultrasmall nanostructures that have attracted growing interest in biomaterial research. Their distinctive characteristics, which include facile synthesis, size-tunable fluorescence, excellent chemical stability, favorable biocompatibility, and inherent antibacterial activity, render them highly suitable for advanced biomedical applications such as multimodal imaging, biosensing, photodynamic therapy, and targeted drug delivery. These advantages position GBQDs as a promising platform for further exploration and expanded utility. This review critically examines how structural and compositional variations in GBQDs govern their optical, electronic, and surface properties, which in turn define their specific roles in bioimaging, biosensing, drug delivery, photodynamic therapy, and antibacterial treatments. A comparative analysis is provided between graphene quantum dots (GQDs) and graphene oxide quantum dots (GOQDs), highlighting subtle differences in structure and properties that inform their respective application scopes, with dedicated attention to evaluating biocompatibility and potential toxicity. Expanding on the biocompatibility assessment, the analysis also addresses the ongoing debate on toxicity by evaluating key factors like size, surface chemistry, dosage, and exposure pathways. By integrating perspectives across these biomedical domains, the review emphasizes the interconnected roles of material design, functionalization, and safety assessment. Finally, major challenges to clinical translation are outlined, including synthesis reproducibility, long-term biodistribution, and degradation mechanisms. Strategic research priorities are proposed to facilitate the transition of GBQDs from laboratory innovation to practical therapeutic applications.

Although Ti implants have been used clinically for decades, their osseointegration is still a major concern in aged, diseased and osteoporotic patients. Using a hydrothermal synthesis approach, monetite (CaHPO₄) and Co-monetite coatings with controlled crystallinity and surface topography were designed and produced. Structural characterization via X-ray diffraction (XRD) confirmed the formation of phase-pure monetite (triclinic) with homogeneous cobalt distribution, while scanning electron microscopy (SEM) and profilometry revealed microstructured surfaces featuring peaks and valleys, mimicking native bone morphology. Remarkably, the coatings exhibited superhydrophilic properties for Co-monetite versus uncoated Ti. Biological assessments demonstrated excellent cytocompatibility using preosteoblasts, with MTT assays showing higher metabolic activity in Co-monetite groups compared to control. SEM analysis revealed enhanced preosteoblast adhesion and spreading on Co-monetite surfaces by day 7. Gene expression profiling uncovered significant upregulation of osteogenic markers, while zymography further demonstrated increased both MMP-2/9 activity, indicating active extracellular matrix remodeling. Altogether, these findings highlight the dual functionality of Co-monetite coatings toward (1) the physicochemical properties that promote osteoblast adhesion and early differentiation, and (2) cobalt doping, that induces a pro-angiogenic response through HIF-1α stabilization. By addressing both osteogenesis and vascularization, two critical challenges in implant integration, this research provides a foundation for the rational design of multifunctional biomaterial coatings for orthopedic and dental applications. The results suggest that Co-monetite coatings are a promising strategy to enhance the osseointegration of bone implants, warranting further preclinical investigation.

Three-dimensional (3D) intestinal models require physiologically relevant microarchitectures and mechanically supportive matrices to accurately replicate epithelial behavior; however, most existing in vitro systems lack villus–crypt topography and do not provide the material cues needed to guide epithelial organization. In this work, we developed biomimetic silk fibroin (SF) membranes that reproduce the native villus–crypt structure using two complementary cross-linking and processing strategies: chemical cross-linking with BDDE to form soft hydrogels and ethanol-induced β-sheet formation to generate stiff, dimensionally stable membranes. These routes were selected because they produce distinct material classes with nonoverlapping ranges of crystallinity, hydrophilicity, and stiffness, enabling access to mechanical regimes unattainable through a single cross-linking method. Villus–crypt architectures were replicated with high fidelity using customized molds. By culturing Caco-2 cells on these patterned SF membranes, we systematically examined how matrix stiffness and β-sheet content influence epithelial adhesion, proliferation, and differentiation. The physically cross-linked membranes (∼20 MPa) supported robust spreading, confluent monolayer formation, and relatively high ALP activity, whereas the softer hydrogels (∼15 kPa) limited adhesion and proliferation. Collectively, this study establishes a tunable SF-based platform that provides both physiological topography and mechanical support, offering a promising foundation for advanced 3D in vitro intestinal epithelial models.

Magnesium alloys are promising biodegradable implant materials, but their rapid corrosion in physiological environments limits their clinical applications. This work is focused on the development of cementitious coatings inducing magnesium phosphate formation on magnesium AZ31 alloys. First, the alloy surfaces immersed in orthophosphoric acid (OPA) solutions with six additives of various functions (sodium chloride, magnesium chloride, calcium nitrate, magnesium nitrate, trisodium citrate, and hydroxyethyl cellulose (HEC)) were comparatively analyzed to understand the effect of solution chemistry on surface evolution. OPA solutions were also saturated with respect to magnesium ions, which effectively limited surface degradation. Sample mass and solution pH were monitored for 21 days, and depositions were characterized using SEM, EDX, and electrochemical methods to identify the surface composition and investigate its effectiveness against Mg degradation. In the next stage, alloy plates were dip-coated with the multicomponent suspension of the most effective composition (OPA, MgCl₂, HEC, and Mg-saturated deionized water). The phase evolution of the dried samples in 3.5 wt % NaCl solution was monitored with regular gravimetric, pH, quantitative XRD, SEM, EDX, and electrochemical Tafel analyses. Samples passivated despite the high chlorine concentration, as initially formed newberyite crystals, were replaced by Mg oxychlorides, Mg phosphates, and Mg hydroxide in order, in response to the shift in solution pH from acidic to alkaline values that is driven by the dissolution and transformation of the alloy and coating phases. Thermally cross-linking HEC improved the stability of the coatings, which slightly retarded the degradation kinetics. In vitro cell culture tests validated the coated AZ31 as both being biocompatible and potentially bioactive. Thus, the phosphatizing coating approach offers a promising strategy for controlled biodegradation of magnesium implants in physiological environments.

Acute inflammation is marked by the excessive and unregulated recruitment of neutrophils to inflamed or injured areas, which contribute to severe tissue damage in numerous inflammatory diseases. Therefore, precise control of the recruitment of neutrophils to inflammation sites is an appealing method to prevent neutrophilic injury. In this study, we investigate the impact of polymerized salicylic acid particles on modulating neutrophil function, focusing on how targeting the inflamed vasculature with particulate carriers influences the recruitment of neutrophils to sites of inflammation. We find that both vascular-targeted and untargeted Poly-SA particles reduce neutrophil rolling and transmigration in murine models of acute mesenteric and lung inflammation. However, the performance of vascular-targeted particles varied depending on the targeting strategy used to target the inflamed endothelium. Our work provides initial insights into the impact of targeted particulate carriers on neutrophil function, offering guidance on future design considerations for drug carriers aimed at modulating neutrophilic inflammation.