ACS Biomaterials Science & Engineering最新文献

Titanium alloys are commonly used for bone replacement due to their excellent corrosion resistance. However, they can cause stress shielding due to their high stiffness. Consequently, porous titanium scaffolds can be designed to reduce the elastic mismatch with bone, and further hydrogel coatings can be applied to mimic the extracellular microenvironment. In this work, gyroid titanium scaffolds were coated with a bioactive alginate-gelatin hydrogel. The addition of 45S5 bioactive glass enhanced the mechanical properties of the hydrogel and its adhesion strength. Furthermore, the developed hydrogels allowed for the penetration of gyroid scaffolds, demonstrating the potential of bioactive coatings for titanium implants.

Silk fibroin (SF) and gelatin methacryloyl (GelMA)-based hydrogels are emerging as promising biomaterials for various biomedical applications due to their unique physiological and physicochemical properties. This Review highlights the synergistic advantages of SF/GelMA hydrogels, focusing on their physicochemical tunability, biocompatibility, and multifunctionality. SF contributes to structural integrity and mechanical strength through the formation of crystalline β-sheet domains, while GelMA provides a photo-cross-linkable functionality, facilitating precise modulation of mechanical and structural properties beneficial for cell support. Various cross-linking strategies, including physical (ionic, hydrogen bonding, hydrophobic interaction, and crystalline formation) and chemical (covalent cross-linking, photo-cross-linking, and enzymatic), are explored to optimize SF/GelMA hydrogels for enhanced tissue adhesion and tissue (skin, muscle, cartilage, bone, tendon, and ligament) regeneration applications. Furthermore, we address the current key translational challenges such as long-term biostability, large-scale production, and immune-regulatory pathways for successful clinical implementation for applications in regenerative medicine, including tissue repair and tissue reconstruction.

The development of suitable hydrogels as delivery vehicles for neural stem/progenitor cells (NSPCs) is ongoing. Most injectable hydrogels for NSPC delivery either are mechanically fragile or do not promote the desired cell morphological changes during neural differentiation or cell-cell interactions during mature synapse formation. In this report, the utility of a gelatin microgel-based injectable hydrogel is explored for the encapsulation of NSPCs with the purpose of generating functional neurons. In addition, we describe facile enzymatic chemistry for the conjugation of bioactive proteins, such as laminin, to the surface of gelatin microgels to improve cell adhesion and organization of encapsulated cells. Encapsulation in the microgel assembly with immobilized laminin substantially improved NSPC viability compared with the nonporous hydrogel with the same chemical composition and resulted in enhanced neural differentiation (both neuronal and glial) with physiologically relevant morphological changes and cell-cell connections evidenced by immunofluorescence imaging. The firing of functional neurons when stimulated by glutamate was confirmed by calcium flux imaging after 4 weeks of differentiation. These results indicate the potential usage of gelatin microgels as an injectable formulation for NSPC delivery for neural tissue regeneration.

As a novel cancer treatment method, photothermal therapy (PTT) is considered an up-and-coming candidate for cancer treatment owing to its low invasiveness and ease of implementation. Nevertheless, single PTT in the first transparency (NIR-I, 750–1000 nm) biowindows is often insufficient to eliminate tumor cells due to light scattering and absorption at the tumor site. Therefore, the rational design of multifunctional nanocomposites for multimodal combination therapies based on PTT is attractive for improving treatment efficacy while reducing drug resistance and adverse reactions. Herein, we report a smart multifunctional nanocomposite DOX-Mo₂C-PAA/Apt-M (DMPM) based on molybdenum carbide (Mo₂C) MXene for active targeted photothermal-chemotherapy in the second transparency (NIR-II, 1000–1350 nm) biowindows. This nanocomposite effectively absorbed light and converted it into heat, achieving a photothermal conversion efficiency of 38.64% under NIR-II laser irradiation. Meanwhile, the DMPM nanocomposite exhibited pH and laser dual-stimuli-triggered doxorubicin (DOX) release in the tumor microenvironment. Furthermore, DMPM could effectively target MCF-7 solid tumors, significantly improving therapeutic efficacy. In vitro and in vivo studies confirmed that DMPM triggered significant cellular killing and tumor eradication without systemic toxicity. Our work not only presents a new approach for multimode cancer treatment but also expands the application of Mo₂C MXene in the biomedical field.

Macrophage polarization critically shapes the local immune microenvironment during bone implant osseointegration and can be modulated by implant surface nanotopography. Unfortunately, the underlying mechanisms still need to be elucidated. Previously our group has confirmed the macrophage polarization rules on titania nanotube arrays (NT) with different diameters. In the present study, we wonder whether mitochondria are involved, considering their significant role in macrophage polarization. The NT surface with a larger diameter (∼100 nm) could induce M1 polarization, accompanied by more active mitochondrial fission and depolarization, as indicated by increased mitochondrial number, reactive oxygen species (ROS) generation, mtDNA/nDNA ratio, and reduced JC-1 aggregation. Further RNA-sequencing revealed the selective upregulation of decorin on nanotube surfaces with larger diameters, and macrophage M1 polarization was diminished after decorin downregulation. As a versatile extracellular matrix molecule, decorin bridges the gap between implant surface nanotopography and mitochondria responses. These findings reveal a mitochondria-centered mechanism whereby implant nanoarchitecture directs immune responses, providing a novel target for designing immunomodulatory biomaterials.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, significantly impacting the quality of life. Traditional treatments for RA, including synthetic and biological disease-modifying antirheumatic drugs (DMARDs), are limited by issues such as systemic side effects, nonspecificity, and patient compliance challenges. Recently, hydrogel-based drug delivery systems have emerged as promising alternatives, providing localized, sustained, and stimuli-responsive therapeutic release. Hydrogels, with their high-water content and biocompatibility, enable the encapsulation and controlled delivery of various drugs including DMARDs, corticosteroids, and immunomodulatory agents. This review provides a comprehensive overview of recent advancements in hydrogel-based strategies for RA treatment, focusing on three key applications: (1) sustained DMARD delivery, (2) composite hydrogels integrating nanomaterials to impart additional disease-modifying properties such as targeted and controlled release of multiple drugs, including hydrophobic ones, and (3) hydrogel-mediated immunosuppressive cell delivery. By leveraging these multifunctional capabilities, hydrogels offer innovative solutions to overcome key challenges in conventional RA therapies. Although challenges in stability and scalability remain, ongoing advancements in hydrogel technology hold significant potential to transform RA management.

This study demonstrates the use of spray drying as a versatile processing technique to produce regenerated silk powders with a controllable particle size and solubility. After overcoming silk’s shear sensitivity and establishing a usable processing window, semicrystalline silk powders were produced. The impact of silk properties and spray drying conditions on powder properties was then explored. Spray drying produced spherical hollow or collapsed particles similar to other spray dried proteins; particle size could be controlled from a d(50) of less than 5 to almost 40 μm through altering feedstock concentration. Interestingly, the silk secondary structure, which typically dictates silk solubility, was resilient to changes in spray drying conditions: all powder samples ranged from 39 to 42% β-sheet content. Yet despite these findings, silk solubility could be controlled from less than 4% to nearly 60% purely by changing fibroin molecular weight and, to a lesser extent, concentration. Given the commercial viability of spray drying, this study demonstrates significant potential for the production of powders with controllable properties for a range of possible applications, from biomaterials to food or cosmetic applications.

The glycocalyx (GCX), a multicomponent coating on endothelial cells (ECs), plays a critical role in various cellular behaviors, including barrier formation, vasodilation, and mechanotransduction. Mechanical perturbations in the vascular environment, such as blood vessel stiffness, are sensed and transduced by ECs via the GCX. Hypertension-induced stiffness disrupts GCX-mediated mechanotransduction, leading to EC dysfunction and atherosclerotic cardiovascular diseases. Understanding GCX-regulated mechanotransduction necessitates an in vitro model that closely mimics in vivo conditions. Existing models are insufficient, prompting the development of the system described in this manuscript. Here, we report on a new system to model varying EC substrate stiffness under sustained physiological fluid shear stress, providing a realistic environment for comprehensive examination of EC function. Gelatin methacrylate (GelMA) substrates with stiffnesses of 5 kPa (physiological) and 10 kPa (pathological) were seeded with human umbilical vein ECs (HUVECs) and subjected to constant physiological shear stress (12 dyn/cm²) for 6 h. Analysis focused on heparan sulfate (HS), sialic acid (SA), hyaluronic acid (HA), syndecan-1 (SDC1), cluster of differentiation 44 (CD44), and Yes-associated protein (YAP). Compared to the 5 kPa conditions, HS coverage and thickness decreased at 10 kPa, indicating impaired barrier function and increased susceptibility to inflammatory agents. SA density increased despite decreased coverage, suggesting enhanced binding site availability for inflammatory recruitment. HA expression remained unchanged, but the amount of the HA core receptor, CD44, was found to be increased at 10 kPa. Consistent with previously published interactions between CD44 and YAP, we observed increased YAP activation at 10 kPa, as evidenced by increased nuclear translocation and decreased phosphorylation. These findings, bridging biomaterials and mechanobiology approaches, deepen our understanding of how mechanical stimuli influence the EC GCX function. The results underscore the potential of mechanotherapeutic strategies aimed at preserving vascular health by modulating the endothelial function.

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.

In recent decades, inertial microfluidic devices have been widely used for cell separation. However, these techniques inevitably exert mechanical stresses, causing cell damage and death during the separation process. This remains a significant challenge for their biological and clinical applications. Despite extensive research on cell separation, the effects of mechanical stresses on cells in microfluidic separation have remained insufficiently explored. This review focuses on the effects of mechanical stresses on cells, particularly in spiral microchannels and contraction–expansion arrays (Contraction and Expansion Arrays (CEAs)). We derived the approximated magnitude of shear stress in a spiral microchannel, extensional stress in CEAs and conventional methods, along with exposure time in a single map to illustrate cell damage and operational zones. Finally, this review serves as a practical guideline to help readers in evaluating stress damages, enabling the effective selection of appropriate techniques that optimize cell viability and separation efficiency for biological and clinical applications.