The fields of tissue engineering and regenerative medicine have made astounding progress in recent years, evidenced by cutting-edge 4D printing technologies, precise gene editing tools, and sustained long-term functionality of engineered tissue grafts. Despite these fantastic feats, the clinical success of tissue-engineered constructs so far remains limited to only those relatively simple types of tissues such as thin bilayer skin equivalents or avascular cartilage. On the other hand, volumetric tissues (larger than a few millimeters in all dimensions), which are highly desirable for clinical utility, suffer from poor oxygen supply due to limited dimensional diffusion. Notably, large, complex tissues typically require a vascular network to supply the growing cells with nutrients for metabolic demands to prolong viability and support tissue formation. In recognition, extensive efforts have been made to create vascular-like networks in order to facilitate mass exchange through volumetric scaffolds. This review underlines the urgent need for continued research to create more complex and functional vascular networks, which is crucial for generating viable volumetric tissues, and highlights the recent advances in sacrificial template-enabled formation of vascular-like networks.

X-rays, a form of ionizing radiation with high energy and significant penetration capability, are commonly used in clinical tumor treatment through radiotherapy. Despite their widespread use, optimizing X-ray efficacy remains a critical challenge due to issues such as radiation resistance and damage to surrounding health tissues. Recent advancements in nanotechnology have introduced new opportunities and challenges in cancer diagnosis and treatment. This review summarizes the latest progress in nanomaterials for X-ray-triggered cancer therapy, highlighting their various advantages such as targeted delivery, reduced side effects, and enhanced therapeutic efficacy. We examine how nanomaterials, including metals, metal oxides, metal sulfides, metal fluorides, rare earth oxides, cluster compounds, metal-organic frameworks, and nanohybrids, enhance the effectiveness of X-ray-triggered treatments. Furthermore, we address the current challenges and future prospects of efficient X-ray-triggered cancer therapy, aiming to provide a comprehensive overview for researchers and clinicians in the field.

Liver fibrosis is a pathological process resulting from prolonged exposure to various injury factors. It is characterized by the abnormal proliferation and activation of hepatic stellate cells and excessive deposition of extracellular matrix. If left untreated, it can progress to cirrhosis, liver failure, and even liver cancer. There is currently no efficient and accurate clinical diagnostic method for early liver fibrosis. Therefore, there is an urgent need to address the challenge of accurate staging and early diagnosis of liver fibrosis in clinical practice. Recently, nanomaterials have demonstrated significant potential for enhancing the diagnosis of liver fibrosis. Nanomaterials possess the ability to precisely identify and target the microenvironment associated with liver fibrosis. By enhancing their enrichment in the target area, nanomaterials can improve imaging contrast of fibrosis lesions in the liver, thereby enabling accurate diagnosis of liver fibrosis. Accordingly, this review delves into the latest research and advancements concerning nanomaterials in liver fibrosis diagnosis.

Hydrogen as a therapeutic agent has attracted a great deal of attention because of its superior therapeutic outcome on many diseases, including inflammatory injury, tumors, metabolic disorders, and neurological diseases. Photocatalytic hydrogen evolution has emerged as a promising strategy for hydrogen production and delivery. This review article presents the recent developments in the design and synthesis of conjugated polymer materials, including linear polymers and crosslinked conjugated materials, for photocatalytic hydrogen evolution. Particularly, we focus this review on the development of conjugated polymers as photocatalysts and the resulting hydrogen therapy in the fields of anti-inflammatory, free radical scavenging, and cancer treatment. Finally, this article discusses the future research and perspective of conjugated polymer materials for hydrogen evolution and the potential clinical applications of hydrogen as a therapeutic agent.

The RNA found in the circular system is known as extracellular RNA (exRNA). This kind of RNA has been found to play a biological role similar to that of a messenger. They can be used as indicators of disease status or the physiological health of an organism. A large number of RNA-based biomaterials have been developed by simulating the biological function and structure of natural RNA molecules. The structural programmability of RNA-based biomaterials provides the spur for scientists to pioneer new approaches in disease detection and prevention. Nevertheless, the link between exRNA function and the design of RNA-based biomaterials has not been fully understood. Understanding the biological structure and function of exRNA will contribute to the clinical translation of this novel biotechnology. The present review discusses the research progress associated with exRNA and their derivatives to bridge the gap between natural exRNA and RNA-based biomaterials.

Extranodal NK/T cell lymphoma (ENKTL) poses significant challenges in efficient treatment processes due to its aggressive nature and high recurrence rates. There is a critical need to develop a robust statistical model to predict treatment efficacy by dynamically quantifying biomarkers tailored to various stages of lymphoma. Recent analytics such as sequencing and microbiome tests have only been utilized to understand lymphoma progression and treatment response in clinical settings. However, these methods are limited by their quantitative analysis capabilities, long turnaround times, and lack of single-cell resolution, which are essential for understanding the heterogeneous nature of lymphoma. In this study, we developed a deep learning-enhanced image cytometry (DLIC) to investigate biophysical heterogeneities in peripheral blood mononuclear cells (PBMCs) from newly diagnosed (ND) ENKTL patients. We established a substantial cohort of 23 ND ENKTL patients, categorizing them into interim of treatment (n = 21) and end of treatment (n = 19) stages along their serial treatment timelines. Using a basic optical microscope and a commercial microchip, we analyzed over 270,000 single PBMCs in high-throughput, profiling their size, eccentricity, and refractive index in a completely label-free and quantified manner through AI-based nanophotonic computation. We observed distinct heterogeneity variations in these three biophysical indicators across treatment stages and relapse statuses, revealing solid mechanistic correlations among the phenotypes. We established a three-dimensional single-cell distribution map for ENKTL patients and created a standard for quantifying the change in occupational volume. Leveraging this extensive database, DLIC offers on-site analytics in clinical settings, facilitating treatment assessment and prognosis prediction through label-free biophysical analysis of patient PBMCs, extracted directly without additional sample preparation.

The liver is an immune organ, especially an immune tolerance organ. The critical shortage of donor organs and disease models for the treatment of end-stage liver failure underscores the urgent need for the generation of liver organoids from human induced pluripotent stem cells (iPSCs). Notably, significant advancements have been made in the study of liver organoids over the past decade. The construction of liver organoids has transitioned from single cell type to multicellular models, and from two-dimensional to three-dimensional cultures. Here we provide the progress surrounding the different liver organoids culture techniques from 3D printing to organ-on-chip, as well as focuses on the present and future applications of liver organoids, and then to present challenges and perspectives ahead for further advancement.

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.

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.

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.