Biomaterials research最新文献

Self-propelled micro/nanomotors (MNMs), which can convert other energy into mechanical motion, have attracted considerable attention due to their potential applications in diverse fields. Due to the asymmetric structures and 2 or more chemically discrepant composites constructed in the Janus nanoparticles, asymmetrical forces can be created in the physical environment. Thus, MNMs with Janus structures have been widely studied for revealing possible driving mechanisms. This tutorial review covers the most representative examples of Janus-structured MNMs developed so far, which are self-propelled by different mechanisms. We focus on Janus MNMs that exhibit self-propelled motion in liquid environments and their potential applications in biomedicine, including drug delivery, cancer therapy, bioimaging, and biosensing. The driving mechanisms and challenges associated with constructing asymmetric fields are deeply discussed, along with future opportunities for these versatile and promising MNMs. This review provides an overview of the rapidly evolving field of MNMs and their potential applications, serving as a valuable resource for researchers and others interested in this field.

Although extensive antibiotic regimens have been implemented to address pathogen-infected pneumonia, existing strategies are constrained in their efficacy against intracellular bacteria, a prominent contributor to antibiotic resistance. In addition, the concurrent occurrence of a cytokine storm during antibiotic therapy presents a formidable obstacle in the management of pneumonia caused by pathogens. In the present study, an infection-targeting system that leverages M2-macrophage-derived vesicles [exosomes (Exos)] as vehicles to convey antibiotics (antibiotics@Exos) was developed for effective pneumonia management. The proposed system can enable antibiotics to be specifically delivered to infected macrophages in pneumonia through homotypic recognition and was found to exhibit an exceptional intracellular bactericidal effect. Moreover, M2-type vesicles exhibit a high degree of efficiency in reprogramming inflammatory macrophages toward an anti-inflammatory phenotype. As a result, the administration of antibiotics@Exos was found to substantical decrease the level of the infiltrated inflammatory cells and alleviate the inflammatory factor storm in the lungs of acute lung injury mice. This intervention resulted in the alleviation of reactive-oxygen-species-induced damage, reduction of pulmonary edema, and successful pneumonia treatment. This bioactive vesicle delivery system effectively compensates for the limitations of traditional antibiotic therapy regimens with pluralism effects, paving a new strategy for serious infectious diseases, especially acute pneumonia treatment.

Persistent synovitis is a pivotal pathological feature of rheumatoid arthritis (RA). However, the current rheumatoid drugs are accompanied by severe side effects and have limited anti-inflammatory capabilities. In this work, we designed a bioactive material-folic acid modified layered double hydroxides (FA-LDH), aiming at targeting M1 macrophages and modulating macrophage repolarization. The in vitro experiment showed that FA-LDH mitigated the release of proinflammatory cytokines and promoted the expression of M2 macrophage markers. In terms of the action mechanism, FA-LDH modulated the nucleocytoplasmic transport of the small mothers against decapentaplegic 5 (Smad5) protein by adjusting the pH within the immune microenvironment. Subsequently, relying on the interaction between phospho-Smad5 (pSmad5) and p65, the nuclear factor kappa B signaling pathway was down-regulated through inhibiting nuclear transport of p65. Additionally, FA-LDH exhibited excellent targeting capability toward M1 macrophages and strong accumulation capacity in inflamed joints. In vivo experiment showed that FA-LDH could relieve swelling of limbs, reduce the infiltration of inflammatory cells, and protect joint cartilage and subchondral bone structure in collagen-induced arthritis mice. In summary, this work introduces a strategy for utilizing bioactive FA-LDH in the treatment of RA, highlighting the potential of FA-LDH to alleviate inflammation and reshape the immune microenvironment through the pSmad5/p65 axis.

Precision medicine is a personalized medical model based on the individual's genome, phenotype, and lifestyle that provides tailored treatment plans for patients. In this context, tumor organoids, a 3-dimensional preclinical model based on patient-derived tumor cell self-organization, combined with digital analysis methods, such as high-throughput sequencing and image processing technology, can be used to analyze the genome, transcriptome, and cellular heterogeneity of tumors, so as to accurately track and assess the growth process, genetic characteristics, and drug responsiveness of tumor organoids, thereby facilitating the implementation of precision medicine. This interdisciplinary approach is expected to promote the innovation of cancer diagnosis and enhance personalized treatment. In this review, the characteristics and culture methods of tumor organoids are summarized, and the application of multi-omics, such as bioinformatics and artificial intelligence, and the digital methods of organoids in precision medicine research are discussed. Finally, this review explores the main causes and potential solutions for the bottleneck in the clinical translation of digital tumor organoids, proposes the prospects of multidisciplinary cooperation and clinical transformation to narrow the gap between laboratory and clinical settings, and provides references for research and development in this field.

Effective drug delivery relies on the selection of suitable carriers, which is crucial for protein-based therapeutics such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). One of the key advantages of TRAIL is its ability to selectively induce apoptosis in cancer cells excluding healthy tissues by binding to death receptors DR4 and DR5, which are highly expressed in various cancer cells. Despite this promise, the clinical application of TRAIL has been limited by its short half-life, limited stability, and inefficient delivery to tumor sites. To overcome currently available clinical and engineering approaches, a series of sophisticated strategies is required: (a) the design of biomaterial-mediated carriers for enhanced targeting efficacy, particularly via optimizing selected materials, composition, formulation, and surface modulation. Moreover, (b) development of genetically modified cellular products for augmented TRAIL secretion toward tumor microenvironments and (c) cell surface engineering techniques for TRAIL immobilization onto infusible cell populations are also discussed in the present review. Among these approaches, living cell-based carriers offer the distinct advantage of systemically administered TRAIL-functionalized cells capturing circulating tumor cells in the bloodstream, thereby preventing secondary tumor formation. This review provides insight into the development of novel TRAIL delivery platforms, discusses considerations for clinical translation, and suggests future directions and complementary strategies to advance the field of TRAIL-based cancer therapeutics.

Oral wounds in diabetes mellitus (DM) often delay healing due to reduced angiogenesis and increased inflammatory response in the local microenvironment, even leading to graft necrosis and implant failure. Therefore, developing an effective program to promote healing is of great clinical value. Much of the current research is focused on promoting wound healing through surface adhesive materials that exert a pro-angiogenic, anti-inflammatory effect. However, the application of surface bonding materials in the oral cavity is very limited due to the humid and friction-prone environment. Decellularized extracellular adipose tissue (DAT) is an easily accessible and biocompatible material derived from adipose tissue. To further explore the potential of DAT, we used multi-omics to analyze its composition and possible mechanisms. Proteomic studies revealed that DAT contains anti-inflammatory, pro-angiogenic proteins that promote DM tissue regeneration. To adapt to the moist and chewing friction environment of the mouth, we modified DAT into a temperature-sensitive hydrogel material that can be injected intramucosally. DAT hydrogel has been verified to promote angiogenesis and exert anti-inflammatory effects through macrophage phenotypic transformation. Meanwhile, transcriptome analysis suggested that the inhibitory effect of DAT on the interleukin 17 signaling pathway might be a key factor in promoting DM oral wound healing. In conclusion, after multi-omic analysis, DAT hydrogel can exert good pro-angiogenic and anti-inflammatory effects through the interleukin 17 signaling pathway and can be adapted to the specific environment of the oral cavity. This provides a potential way to promote DM oral wound healing in a clinical setting.

Immunogenic cell death, triggered by photothermal therapy or specific chemotherapy, strives to establish a positive feedback loop in cancer immunotherapy. This loop is characterized by the rapid release of antigens and adenosine triphosphate (ATP), ultimately leading to accelerated T cell infiltration. However, this loop is hindered by T cell exhaustion caused by adenosine originating from ATP and glucose deprivation in the immunosuppressive microenvironment. To overcome this challenge, we developed a pH-low insertion peptide-functionalized mesoporous-polydopamine-based nanoadjuvant that incorporates adenosine deaminase and doxorubicin (termed as PPMAD). PPMAD aimed to overcome T cell exhaustion by reducing adenosine consumption and providing an alternative carbon source for CD8⁺ T cell function during glucose starvation. First, PPMAD triggered the burst release of antigens and ATP through photothermal therapy and doxorubicin-induced immunogenic cell death, culminating in the expedited infiltration of T cells. Second, adenosine deaminase depleted adenosine, reducing immunosuppressive agents and generating abundant inosine, which served as an alternative carbon source for CD8⁺ T cells. By implementing this "reducing suppression and broadening sources" strategy, we successfully overcome T cell exhaustion, greatly enhancing the effectiveness of cancer immunotherapy both in vitro and in vivo. Our findings highlighted the positive feedback loop between on-demand photothermal therapy, chemotherapy immunotherapy, and achieving complete tumor response.

Acetaminophen (APAP) overdose has long been recognized as the main cause of drug-induced liver injury (DILI), characterized by glutathione (GSH) depletion and reactive oxygen species (ROS) accumulation, leading to ferroptosis and inflammatory responses. There is an urgent need for liver-protective agents to combat ferroptosis, modulate oxidative stress, and ameliorate inflammation. Catechin, a well-known polyphenol compound, has been shown to have antioxidant potential. However, its protective role on APAP-induced liver injury (AILI) has not been elucidated. In this study, we evaluated the modulating effects of catechin on AILI and observed that catechin attenuated liver injury by reducing inflammation. Mechanistically, catechin alleviated hepatic oxidative stress by inhibiting ROS accumulation, malondialdehyde (MDA) production, and GSH depletion. Furthermore, catechin, as a hepatic injury reparative agent, could counteract APAP-induced hepatocyte ferroptosis by activating the xCT/GPX4 pathway, and is expected to be a novel natural inhibitor of ferroptosis. Additionally, the transcriptomic results indicated that the inhibition of Stat1 by catechin is important for the management of AILI. Inhibition of signal transducer and activator of transcription 1 (STAT1) expression, achieved through the use of the STAT1 inhibitor fludarabine in vivo and small interfering RNA (siRNA) in vitro, was confirmed to attenuate APAP-induced ferroptosis. In conclusion, the present study identified a novel natural drug inhibitor of ferroptosis and revealed its mechanism of action to inhibit ferroptosis, regulate oxidative stress, and ameliorate inflammation in AILI. This further provides new insights into the novel natural ferroptosis inhibitors for the treatment of ROS-related inflammatory diseases.

Early detection of amyotrophic lateral sclerosis (ALS) progression is critical for improving disease management and therapeutic outcomes. However, the clinical heterogeneity and variability in ALS symptoms often lead to delayed diagnosis and suboptimal therapeutic interventions. Since mitochondrial dysfunction is a hallmark of ALS, we hypothesized that monitoring mitochondrial function could serve as a reliable strategy for early diagnosis and therapeutic monitoring of ALS. To address this, we synthesized and characterized 2 novel near-infrared fluorophores, ALS04 and ALS05, designed to target mitochondria and lysosomes. Their physicochemical properties, serum protein binding, fluorescence characteristics, photostability, and pharmacokinetics were systematically evaluated. We found that benzothiazole-based fluorophores exhibit excellent mitochondrial targeting, optimal optical properties, biocompatibility, and favorable biodistribution in vivo. Interestingly, ALS04 showed superior mitochondrial accumulation compared to ALS05, despite their similar physicochemical properties. This enhanced accumulation can be attributed to the lower molecular weight and higher lipophilicity of ALS04. Real-time fluorescence imaging revealed a substantial reduction in ALS04 signals in mitochondrial-rich tissues such as brown fat, highlighting its potential for monitoring mitochondrial dysfunction in early-stage ALS. Furthermore, the detection of ALS04 in the mouse brain suggests its ability to monitor blood-brain barrier hyperpermeability, another key feature of ALS pathology. These findings establish ALS04 as a promising noninvasive imaging tool for monitoring biomarkers associated with ALS progression. Its ability to detect early-stage pathophysiological changes in an ALS mouse model highlights its potential for advancing our understanding of ALS mechanisms and facilitating the identification of novel therapeutic targets.