ACS Biomaterials Science & Engineering最新文献

Development of radiosensitizers with high-energy deposition efficiency, electron transfer, and oxidative stress amplification will help to improve the efficiency of radiotherapy. To overcome the drawbacks of radiotherapy alone, it is also crucial to design a multifunctional radiosensitizer that simultaneously realizes multimodal treatment and tumor microenvironment modulation. Herein, a multifunctional radiosensitizer based on the Cu₃BiS₃-BP@PEI nanoheterostructure (NHS) for multimodal cancer treatment is designed. Cu₃BiS₃-BP@PEI NHS is able to deposit a high radiation dose into cancer cells, enhancing the radiotherapy effect. Due to the heterostructure and the synergistic effect of Cu₃BiS₃ and black phosphorus (BP), significantly boosted ¹O₂ and •OH generation is obtained under X-ray irradiation, which is promising for extremely efficient radiodynamic therapy. More importantly, the acidic tumor microenvironment (TME) can induce the cycle conversion of Cu²⁺ to Cu⁺, oxidizing glutathione (GSH) and catalyzing intracellular overproduction of H₂O₂ into highly toxic •OH, which thus further enhances reactive oxygen species (ROS) production and reduces GSH-associated radioresistance. Furthermore, Cu₃BiS₃-BP@PEI NHS has an excellent photothermal effect and can effectively transform light into heat. The outcomes of the in vitro and in vivo research confirm that the as-prepared Cu₃BiS₃-BP@PEI NHS has a high synergistic therapeutic efficacy at a low radiation dose. This work provides a viable approach to constructing a multifunctional radiosensitizer for deep tumor treatment with TME-triggered multiple synergistic therapies.

Diabetes exacerbates periodontitis by overexpressing reactive oxygen species (ROS), which leads to periodontal bone resorption. Consequently, it is imperative to relieve inflammation and promote alveolar bone regeneration comprehensively for the development of diabetic periodontal treatment strategies. Furthermore, an orderly treatment to avoid interference between these two processes can achieve the optimal therapeutic effect. Thus, we constructed a sequential sustained release system based on the zeolitic imidazolate framework-8 (ZIF-8)-modified chitosan thermosensitive hydrogel (TOOTH) for diabetic periodontal therapy in this work. Chemically modified tetracycline-3 (CMT-3) and platelet-derived growth factor-BB (PDGF-BB) were loaded in the hydrogel and ZIF-8 for sequential release, respectively, with the aim of reducing inflammation and facilitating tissue regeneration. During the therapy, CMT-3 first escaped from the hydrogel due to degradation and diffusion for ROS elimination. Subsequently, ZIF-8 was dissociated under an acid microenvironment, and PDGF-BB was sustainably released to promote osteogenesis. The release intervals between CMT-3 and PDGF-BB could be regulated by the sizes of ZIF-8. The biocompatible TOOTH exhibited a favorable therapeutic effect for diabetic periodontitis in vitro and in vivo. The sequentially controlled release of CMT-3 and PDGF-BB facilitated by TOOTH holds promise for promoting periodontal tissue regeneration and offers potential for clinical translation.

Granular hydrogels are injectable and inherently porous biomaterials assembled through the packing of microparticles. These particles typically have a symmetric and spherical shape. However, recent studies have shown that asymmetric particles with high aspect ratios, such as fibers and rods, can significantly improve the mechanics, structure, and cell-guidance ability of granular hydrogels. Despite this, it remains unknown how controlled changes in the particle aspect ratio influence the injectability, porosity, and cell-instructive capabilities of granular hydrogels. Part of the challenge lies in obtaining microparticles with precisely tailored dimensions using fabrication methods such as flow-focusing microfluidics or extrusion fragmentation. In this work, we leveraged facile photolithography and photocurable hyaluronic acid to fabricate rod-shaped microparticles with widths and heights of 130 μm and lengths that varied from 260 to 1300 μm to obtain aspect ratios (ARs) of 2, 4, 6, 8, and 10. All AR microparticles formed porous and injectable granular hydrogels after centrifugation jamming. Interestingly, the longest microparticles neither clogged the needle nor fractured after extrusion from a syringe. This was attributed to a relatively low elastic modulus that permitted microparticle pliability and reversible deformation under shear. Cells (NIH/3T3 fibroblasts) mixed with the jammed microparticles and injected into molds remained viable, adhered to the particles' surface, and showed a significant and rapid rate of proliferation over a period of 7 days compared to bulk hydrogels. The proliferation rate and morphology of the cells were significantly influenced by the particle AR, with higher cell numbers observed with intermediate ARs, likely attributable to the surface area available for cell adhesion. These findings showcase the utility of injectable granular hydrogels made with high-aspect-ratio microparticles for biomedical applications.

Nanomedicine is revolutionizing precision medicine, providing targeted, personalized treatment options. Lipid-based nanomedicines offer distinct benefits including high potency, targeted delivery, extended retention in the body, reduced toxicity, and lower required doses. These characteristics make lipid-based nanoparticles ideal for drug delivery in areas such as gene therapy, cancer treatment, and mRNA vaccines. However, traditional bulk synthesis methods for LNPs often produce larger particle sizes, significant polydispersity, and low encapsulation efficiency, which can reduce the therapeutic effectiveness. These issues primarily result from uneven mixing and limited control over particle formation during the synthesis. Microfluidic technology has emerged as a solution, providing precise control over particle size, uniformity, and encapsulation efficiency. In this mini review, we introduce the state-of-the-art microfluidic systems for lipid-based nanoparticle synthesis and functionalization. We include the working principles of different types of microfluidic systems, the use of microfluidic systems for LNP synthesis, cargo encapsulation, and nanomedicine delivery. In the end, we briefly discuss the clinical use of LNPs enabled by microfluidic devices.

Pyrophosphate-stabilized amorphous calcium carbonates (PyACC) are promising compounds for bone repair due to their ability to release calcium, carbonate, and phosphate ions following pyrophosphate hydrolysis. However, shaping these metastable and brittle materials using conventional methods remains a challenge, especially in the form of macroporous scaffolds, yet essential to promote cell colonization. To overcome these limitations, this article describes for the first time the design and multiscale characterization of freeze-cast alginate (Alg)-PyACC nanocomposite scaffolds. The study initially focused on the synthesis of Alg-PyACC powder through in situ coprecipitation. The presence of alginate chains in the vicinity of the PyACC was shown to affect both the powder reactivity and the release of calcium ions when placed in water (XRD, chemical titrations). In vitro cellular assays confirmed the biocompatibility of Alg-PyACC powder, supporting its use as a filler in scaffolds for bone substitutes. In a second step, the freeze-casting process was carried out using these precursor powders with varying rates of inorganic fillers. The resulting scaffolds were compared in terms of pore size and gradient (via SEM, X-ray microtomography, and mercury intrusion porosimetry). All scaffolds exhibited a pore size gradient oriented along the solidification axis, featuring unidirectional, lamellar, and interconnected pores. Interestingly, we found that the pore size and wall thickness could be controlled by the filler rate. This effect was attributed to the in situ cross-linking of alginate chains by released Ca²⁺ ions from the fillers, which increased viscosity, affecting temperature-driven segregation during the freezing step. Different multiscale organizations of the porosity and spatial distribution of fillers (FEG-SEM) were correlated with changes in the scaffold mechanical properties (tested via uniaxial compression). With such tunable porous and mechanical properties, Alg-PyACC composite scaffolds present attractive opportunities for specific bone substitute applications.

Epilepsy is one of the oldest neurological disorders discovered by mankind. This condition is firmly coupled with unprovoked seizures stimulated by irrepressible neuroelectrical blasts. Orally taken valproate family has been employed for prophylactic management; however, oral administration is not applicable for critical scenarios, thus calling for medication routes fulfilling necessities of immediate innervation. In order to address this shortcoming, sodium valproate entrapped in poly(ethylene oxide)/polyvinylpyrrolidone (PEO/PVP) nanofibrous patches was developed with the aim of sublingual drug delivery. Initially, the production process was designed and optimized via the central composite design (CCD). Nanofiber fabrication was accomplished with a novel device by using the pressurized gyration method. Fabricated biomaterials were chemically, spatially, and thermally inspected. The beanless and homogeneous appearance of both virgin and impregnated nanofibrous patches was morphologically demonstrated via scanning electron microscopy. Additionally, adequately oro-dispersed impregnated patches released more than 90% of their drug content in under a minute. Following in vitro cyto-safety assurance acquired through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay on SH-SY5Y neuroblastoma cells, the protective antiepileptic effect of impregnated patches was affirmed in vivo via pentylenetetrazole kindled-induced Mus musculus animal modeling. The parameter of in vivo behavioral evaluation was the Racine scoring system. Moreover, histopathological distinctions detected between different test groups were highlighted via fluorescence staining. Finally, the oxidative stress was determined according to quantitative variations of malondialdehyde, glutathione, superoxide dismutase, and catalase levels. The overall conclusion herein suggests that sodium valproate-loaded PEO/PVP nanofibrous patches strikingly prevented behavioral, structural, and oxidative deteriorations caused by pentylenetetrazole.

The current lack of therapeutic approaches to demyelinating disorders and injuries stems from a lack of knowledge surrounding the underlying mechanisms of myelination. This knowledge gap motivates the development of effective models to study the role of environmental cues in oligodendrocyte progenitor cell (OPC) maturation. Such models should focus on determining, which factors influence OPCs to proliferate and differentiate into mature myelinating oligodendrocytes (OLs). Here, we introduce a hyaluronic acid (HA) hydrogel system composed of cross-linked HA containing encapsulated HA fibers with swollen diameters similar to mature axons (2.7 ± 0.2 μm). We tuned hydrogel storage moduli to simulate native brain tissue (200-2000 Pa) and studied the effects of fiber presence on OPC proliferation, metabolic activity, protein deposition, and morphological changes in gels of intermediate storage modulus (800 ± 0.3 Pa). OPCs in fiber-containing gels at culture days 4 and 7 exhibited a significantly greater number of process extensions, a morphological change associated with differentiation. By contrast, OPCs in fiber-free control gels maintained more proliferative phenotypes with 2.2-fold higher proliferation at culture day 7 and 1.8-fold higher metabolic activity at culture days 4 and 7. Fibers were also found to influence extracellular matrix (ECM) deposition and distribution, with more, and more distributed, nascent ECM deposition occurring in the fiber-containing gels. Overall, these data indicate that inclusion of appropriately sized HA fibers provides topographical cues, which guide OPCs toward differentiation. This HA hydrogel/fiber system is a promising in vitro scheme, providing valuable insight into the underlying mechanisms of differentiation and myelination.

The unique screw-shape design and microstructure of implants pose a challenge for mechanical debridement in removing biofilms. Biofilms exhibit increased resistance to antimicrobials relative to single planktonic cells, emphasizing the need for effective biofilm removal during periodontal therapy for peri-implantitis treatment. To tackle this issue, our team evaluated the effectiveness of low-temperature plasma (LTP) for disinfecting titanium discs contaminated with multispecies biofilms associated with peri-implantitis, specifically focusing on biofilms matured for 14 and 21 days as well as biofilms that had formed on Straumann^Ⓡ Ti-SLA implants for 21 days. The biofilms included Actinomyces naeslundii, Porphyromonas gingivalis, Streptococcus oralis, and Veillonella dispar, which were grown in anaerobic conditions. These biofilms were subjected to LTP treatment for 1, 3, and 5 min, using distances of 3 or 10 mm from the LTP nozzle to the samples. Control groups included biofilms formed on Ti discs or implants that received no treatment, exposure to argon flow at 3 or 10 mm of distance for 1, 3, or 5 min, application for 1 min of 14 μg/mL amoxicillin, 140 μg/mL metronidazole, or a blend of both, and treatment with 0.12% chlorhexidine (CHX) for 1 min. For the implants, 21-day-old biofilms were treated with 0.12% CHX 0.12% for 1 min and LTP for 1 min at a distance of 3 mm for each quadrant. Biofilm viability was assessed through bacterial counting and confocal laser scanning microscopy. The impact of LTP was investigated on reconstituted oral epithelia (ROE) contaminated with P. gingivalis, evaluating cytotoxicity, cell viability, and histology. The results showed that a 1 min exposure to LTP at distances of 3 or 10 mm significantly lowered bacterial counts on implants and discs compared to the untreated controls (p < 0.017). LTP exposure yielded lower levels of cytotoxicity relative to the untreated contaminated control after 12 h of contamination (p = 0.038), and cell viability was not affected by LTP (p ≥ 0.05); thus, LTP-treated samples were shown to be safe for tissue applications, with low cytotoxicity and elevated cell viability post-treatment, and these results were validated by qualitative histological analysis. In conclusion, the study's results support the effectiveness of 1 min LTP exposure in successfully disinfecting mature peri-implantitis multispecies biofilms on titanium discs and implants. Moreover, it validated the safety of LTP on ROE, suggesting its potential as an adjunctive treatment for peri-implantitis.

Cell membrane-coated nanomaterials are increasingly recognized as effective in cancer treatment due to their unique benefits. This study introduces a novel hybrid membrane coating nanoparticle, termed cancer cell membrane (CCM)-outer membrane vesicle (OMV)@Lip-indocyanine green (ICG), which combines CCMs with bacterial OMV to encapsulate ICG-loaded liposomes. Comprehensive analyses were conducted to assess its physical and chemical properties as well as its functionality. Demonstrating targeted delivery capabilities and good biocompatibility, CCM-OMV@Lip-ICG nanoparticles showed promising photothermal and immunotherapeutic effects in tumor models. By inducing hyperthermia-induced tumor therapy and bolstering antitumor immunity, CCM-OMV@Lip-ICG nanoparticles exhibit a synergistic therapeutic effect, providing a new perspective for the management of cancer.

Atopic dermatitis (AD) is a prevalent skin disorder worldwide. However, many AD medications are unsuitable for long-term use due to low therapeutic efficacy and side effects. Extracellular vesicles (EVs) extracted from Pinctada martensii mucus have demonstrated therapeutic efficacy in AD. It is hypothesized that EVs may exert their activity on mammalian cells through their specific contents. In this study, we analyzed the results of miRNA sequencing of the EVs and investigated the potency of highly expressed miR-100-5p in treating AD. To enhance the therapeutic efficiency of the EVs in AD, we developed oxidized sodium alginate (OSA)-carboxymethyl chitosan (CMCS) self-cross-linked hydrogels as a vehicle to deliver the EVs to BALB/c mice with dermatitis. The miR-100-5p in EVs exhibited a favorable anti-inflammatory function, while the hydrogels provided enhanced skin residency. Additionally, its efficacy in inflammation inhibition and collagen synthesis was demonstrated in in vivo experiments. Mechanistically, miR-100-5p in EVs exerted anti-inflammatory effects by inhibiting the expression of FOXO3, consequently suppressing the activation of the downstream NLRP3 signaling pathway. This study underscores the significance of utilizing OSA-CMCS hydrogels as a vehicle for delivering miR-100-5p in P. martensii mucus-derived EVs for the treatment of AD.