BMEMat最新文献

In this article number 10.1002/bmm2.12125, Jiao Zheng, Jian Zhang and their co-workers developed an automatic metabolism modulator (auto-MMOD) to intervene in the mitochondrial glycolysis process for cascade antitumor therapy. In the engineered auto-MMOD, the co-encapsulated glucose oxidase (GOx) and DNA-silver nanoclusters (DNA-AgNCs) successfully activates the glycolytic intervention-induced release of Ag+, thereby enhancing tumor inhibition and providing the valuable insight into a biological metabolism-mediated antitumor strategy.

Effectively controlling deep non-compressible bleeding remains a major challenge. In this study, by mimicking nanofiber structure and netting blood cells function of fibrin network in blood clots, we develop a novel bioinspired quaternized chitosan nanofiber sponge with distinct blood cells filtration and blood plasma absorption bifunction for rapid hemostasis. The quaternized chitosan nanofiber sponge possesses a unique gradient pore structure with small pores on the outer surface and large pores in the inner part. The outer small pores effectively capture blood cells with a filtration efficiency as high as 91.7%, while the inner large pores endow with an ultrahigh liquid absorption capacity (93 g/g), surpassing previously reported literature records. The quaternized chitosan nanofiber sponge demonstrates a hemostasis time 2.5 times faster than that of the commercial gelatin® hemostatic sponge when treating the rat liver defect bleeding (noncompressible hemorrhage model). When applied to the rabbit arterial injury bleeding (lethal arterial hemorrhage model), the bioinspired nanofiber sponge achieves bleeding control within only 61.6 s, while both commercial gelatin® hemostatic sponge and commercial collagen® hemostatic sponge fail to stop bleeding even after 240 s. This bioinspired nanofiber sponge derived from the physiological coagulation process may hold great potential for pre-hospital and battlefield first aid.

Immune Cellular Therapies (ICT) have revolutionized the treatment of blood cancer and are beginning to show positive outcomes in treating solid tumors. Despite these successes, ICT faces significant challenges, including tumor accessibility, lengthy manufacturing turnaround, and limited long-term effectiveness. Recent advancements in nanomaterials, particularly nanoparticles, have offered promising solutions to these issues. This perspective introduces the current ICT manufacturing pipeline with a focus on solid tumors and showcases recent nanomaterial-mediated practices to enhance ICT. These efforts include the use of cell-targeting magnetic nanoparticles for non-invasive target identification, lipid nanoparticles for in vivo immune cell stimulation, as well as nanoparticle-mediated gene editing and cytokine delivery to enhance immune cell fitness. By better integrating nanoparticles into the design and manufacturing pipelines, we envision that the next generation of ICT could be faster, more efficient, and capable of targeting a broad spectrum of cancers and inflammatory diseases.

Microglial activation is a key driver of neuroinflammation following cerebral ischemic reperfusion injury (CIRI). Exosomes (Exo) derived from bone marrow mesenchymal stem cells (BMSCs) can regulate microglia, causing a transition from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, thereby reducing neuronal apoptosis in post-reperfusion injuries. However, the generation of superior-quality exosomes remains a significant hurdle in this field. We performed three-dimensional (3D) cultivation of BMSCs using a gelatin methacryloyl (GelMA) hydrogel and collected the released exosomes. We conducted experiments using lipopolysaccharide (LPS)-induced BV2 cells, oxygen-glucose deprivation/reoxygenation (OGD/R)- induced HT22 cells, and CIRI mice to verify the effects of 3D-cultured exosomes in regulating microglial activation and alleviating neuronal apoptosis. Based on the cellular and animal experiments, we successfully demonstrated the remarkable efficacy of exosomes derived from 3D-cultured BMSC using a GelMA hydrogel in the context of CIRI. These exosomes effectively mitigated the conversion of microglia to the inflammatory phenotype and facilitated their transition to the anti-inflammatory phenotype, thereby reducing aseptic inflammatory reactions and neuronal apoptosis. This study demonstrated the effectiveness of GelMA-based 3D-cultured exosomes in treating CIRI and introduced innovative concepts and opportunities for addressing this condition with clinical applications.

Bone tissue is richly innervated, and the influence of the nervous system on the physiological and pathological status of bone tissue has emerged as a significant research focus. The recent discovery of the skeletal interoceptive circuits further emphasizes the crucial role of the central nervous system in the control of bone homeostasis. Skeletal interoception represents one of the most intricate mechanisms in the human body for maintaining bone homeostasis, as it involves the orchestrated efforts of skeletal, nervous, immune, and endocrine systems. In this review, we comprehensively introduce the three primary components of the skeletal interoceptive circuitry, including the ascending pathways that perceive and convey signals to the central nervous system, the central neural pathways that process and interpret these signals, and the descending pathways that mediate the regulatory effects on bone tissue. We also discuss how innovative therapeutic strategies can be developed to modulate bone homeostasis by leveraging the most updated findings on skeletal interoceptive circuitry. We anticipate that the application of knowledge on skeletal interoception will lead to a paradigm shift in the field of orthopaedics and biomaterials.

Cellular senescence is characterized by a sustained and irreversible cessation of cell proliferation in response to diverse environmental stimuli. However, senescent cells exhibit strong metabolic activity and release a range of cytokines and inflammatory mediators into the tumor microenvironment, collectively referred to as the senescence-associated secretory phenotype (SASP). In recent years, to develop new therapies for cancers, researchers have conducted extensive studies on the mechanism of cancer cell senescence and revealed that induction of cancer cell senescence could effectively suppress cancer progression. However, it has been documented that cellular senescence not only inhibits cancer initiation but also contributes significantly to cancer progression in some cases. Hence, it is imperative to comprehend the correlation between cellular senescence and tumorigenesis, and discuss the potential utilization of cellular senescence mechanisms to suppress cancer progression, which lays a theoretical foundation for new drugs to treat cancers. In this review, we first provide an overview of the discovery of cellular senescence and its key milestone events. Meanwhile, this review examines the major stimulus for the induction of senescence, and provides an overview of the categorization of cellular senescence. Subsequently, an examination of the primary regulatory mechanisms of cellular senescence is discussed, followed by a summary of the control of the SASP expression and its dual biological roles in cancers. Additionally, we also provide an overview of common biomarkers utilized in the identification of cellular senescence. Finally, this review investigates the efficacy of the “One-Two punch” sequential treatment approach for cancers, and examines the emerging challenges of this novel approach.

Chronic wounds are wounds that are difficult to heal or do not follow the normal healing process. These include pressure ulcers, diabetic ulcers, venous ulcers, and arterial incomplete ulcers. Unlike acute wounds, chronic wounds are often difficult to heal or even do not heal. Its pathogenesis involves many factors; bacterial infection is the main cause of chronic wound. With the increase in population aging, the incidence of chronic wounds has become a critical issue in the current medical and health field. Management of chronic wounds is faced with the problems of long treatment time, difficulty, high cost, repeated attacks and high disability rate, which seriously threaten patients' ability to take care of themselves in normal life and cause a heavy burden to individuals, families and society. Over the past few years, the development of antibacterial hydrogels for the treatment of bacterial infections has received a lot of attention. Since antibacterial hydrogels not only have the mechanical properties of hydrogels, high biocompatibility and adjustable functional structure, but also have excellent antibacterial properties, they may be an ideal dressing to solve the problem of chronic wound healing. This article introduces the types of chronic wounds, their healing characteristics, and the challenges faced in treating chronic wounds. It classifies antimicrobial hydrogels based on their antimicrobial modes and further discusses the advancements in smart antimicrobial hydrogels along with the benefits and obstacles of using antimicrobial hydrogels in the treatment of chronic wounds. This article also explores the development directions of antimicrobial hydrogels for chronic wound management.

Brain-computer interface (BCI) is an advanced technology that establishes a direct connection between the brain and external devices, enabling high-speed and real-time information exchange. In BCI systems, electrodes are key interface devices responsible for transmitting signals between the brain and external devices, including recording electrophysiological signals and electrically stimulating nerves. Early BCI electrodes were mainly composed of rigid materials. The mismatch in Young's modulus between rigid electrodes and soft biological tissue can lead to rejection reactions within the biological system, resulting in electrode failure. Furthermore, rigid electrodes are prone to damaging biological tissues during implantation and use. Recently, flexible electrodes have garnered attention in the field of brain science research due to their better adaptability to the softness and curvature of the brain. The design of flexible electrodes can effectively reduce mechanical damage to neural tissue and improve the accuracy and stability of signal transmission, providing new tools and methods for exploring brain function mechanisms and developing novel neural interface technologies. Here, we review the research advancements in neural electrodes for BCI systems. This paper emphasizes the importance of neural electrodes in BCI systems, discusses the limitations of traditional rigid neural electrodes, and introduces various types of flexible neural electrodes in detail. In addition, we also explore practical application scenarios and future development trends of BCI electrode technology, aiming to offer valuable insights for enhancing the performance and user experience of BCI systems.

Biological hydroxyapatite (BHA) has been widely used in alveolar bone augmentation, while unfavorable outcomes can still be encountered. Among several reasons, we noticed a chaotic granule size application issue. The principle behind the choice of proper granule size mainly lies in the fitness of defect shape and size. However, granule size has been shown to elicit significant biological effects, with the underlying mechanisms still unknown. BHA granules of five different sizes were first prepared and characterized to investigate their biological effects. We found that the biomimetic porous structure of BHA gradually disappeared with decreasing size, affecting the structure of the blood clot fibrin network, leading to different local immune microenvironments and foreign body reactions (FBRs). Among them, <0.2 mm BHA granules completely lost their biomimetic porous structure and their fibrin network was loosened with strong immune response and strongest FBR. We found Gata3 (+)/Nfat3 (+) Th2 cells were recruited from activated systemic immune organs, inducing CD206 (+)/CD163 (low) M2 macrophages through direct contact with Ptprc-Mrc1, thereby promoting their fusion to form foreign body giant cells leading to strong FBR. This study expanded the understanding of the size effect of BHA granules from a biological perspective and unveiled the mechanisms of systemic immune towards BHA mediated FBR, providing regulatory targets to improve bone regeneration outcomes.

Cancer immunotherapy has appeared as a prospective therapeutic modality. Therapeutic antibodies induced in an in vitro expression system act as “targeting missiles” against tumor-associated binding sites, and subsequently, immune system attack on tumors is restored or boosted. These antibody regimens are engineered towards enhanced Fc efficacy, humanization, and fragmentation to specifically recognize and bind to effective tumor-associated targets. The challenge lies in obtaining efficient therapeutic regimens with low response rates, acquisition of resistance, and immune-related undesirable effects of artificially designed therapeutic antibodies, which is crucial for enhancing clinical efficacy. This review provides an in-depth introduction to antibodies that perform direct/indirect roles in cancer treatment by binding to immune checkpoints, co-stimulatory receptors, and extracellular membrane receptors. It also discusses how antibodies kill tumors and modulate microenvironment of tumor through these targets. The classification of expression systems for antibody production is summarized to guide appropriate selection based on different specificities. Understanding antibody sources, ongoing evaluation of engineered antibodies, and tumor-associated antigen research pave the way for designing appropriate antibody-based immunotherapy regimens.