Vacuoles are unique organelles of fungi. The development of probes targeting the vacuoles membrane will enable visualization of physiological processes and precise diagnosis and therapy. Herein, a zwitterionic molecule, MXF-R, comprising of an aggregation-induced emission (AIE) photosensitizing unit and an antibiotic moxifloxacin, was found capable of specifically imaging vacuole membrane and using for targeted antifungal therapy. MXF-R demonstrated a higher signal-to-noise ratio, stronger targeting capability, and better biocompatibility than the commercial probe FM4-64. By using MXF-R, real-time visualization of vacuole formation during () proliferation was achieved. More importantly, owing to its varying staining ability towards different fungus, MXF-R could be used to quickly identify in mixed strains by fluorescence imaging. Moreover, MXF-R exhibits a remarkable ability to generate reactive oxygen species under white light, effectively eradicating by disrupting membrane structure. This antifungal therapy of membrane damage is more effective than clinical drug fluconazole. Therefore, this work not only presents the initial discovery of a probe targeting vacuolar membrane, but also provides a way to develop novel materials to realize integrated diagnosis and therapy.

The effect of mechanical cues on cellular behaviour has been reported in multiple studies so far, and a specific aspect of interest is the role of mechanotransductive proteins in neuronal development. Among these, yes-associated protein (YAP) is responsible for multiple functions in neuronal development such as neuronal progenitor cells migration and differentiation while myocardin-related transcription factor A (MRTFA) facilitates neurite outgrowth and axonal pathfinding. Both proteins have indirectly intertwined fates via their signalling pathways. There is little literature investigating the roles of YAP and MRTFA concerning neurite outgrowth in mechanically confined microenvironments. Moreover, our understanding of their relationship in immature neurons cultured within engineered confined microenvironments is still lacking. In this study, we fabricated, via two-photon polymerization (2PP), 2.5D microgrooves and 3D polymeric microchannels, with a diameter range from 5 to 30 μm. We cultured SH-SY5Y cells and differentiated them into immature neuron-like cells on both 2.5D and 3D microstructures to investigate the effect of mechanical confinement on cell morphology and protein expression. In 2.5D microgrooves, both YAP and MRTFA nuclear/cytoplasmic (N/C) ratios exhibited maxima in the 10 μm grooves indicating a strong relation with mechanical-stress-inducing confinement. In 3D microchannels, both proteins' N/C ratio exhibited minima in presence of 5 or 10 μm channels, a behaviour that was opposite to the ones observed in the 2.5D microgrooves and that indicates how the geometry and mechanical confinement of 3D microenvironments are unique compared to 2.5D ones due to focal adhesion, actin, and nuclear polarization. Further, especially in presence of 2.5D microgrooves, cells featured an inversely proportional relationship between YAP N/C ratio and the average neurite length. Finally, we also cultured human induced pluripotent stem cells (hiPSCs) and differentiated them into cortical neurons on the microstructures for up to 2 weeks. Interestingly, YAP and MRTFA N/C ratios also showed a maximum around the 10 μm 2.5D microgrooves, indicating the physiological relevance of our study. Our results elucidate the possible differences induced by 2.5D and 3D confining microenvironments in neuronal development and paves the way for understanding the intricate interplay between mechanotransductive proteins and their effect on neural cell fate within engineered cell microenvironments.

Inflammatory bowel disease (IBD) is a chronic recurrent disease with an increasing incidence year by year. At present, no safe and effective treatment for IBD exists. Thus, there is an urgent need to create new therapeutic options that have decreased adverse effects and positive clinical efficacy. A range of nanomaterials have fueled the advancement of nanomedicine in recent years, which is establishing more appealing and prospective treatment approaches for IBD. However, traditional synthetic nanomaterials still have some problems in the IBD drug delivery process, such as weak targeting ability of vectors, difficulty escaping immune surveillance, and poor biosecurity. Natural sources of biological nanomaterials have been identified to solve the above problems. A drug delivery system based on bionic technology is expected to achieve a new breakthrough in the targeted therapy of IBD by nanotechnology due to its organic integration of low immunogenicity and natural targeting of biological materials and the controllability and versatility of synthetic nanocarrier design. We begin this review by outlining the fundamental traits of both inflammatory and healthy intestinal microenvironments. Subsequently, we review the latest application of a cell-derived bionic drug delivery system in IBD therapy. Finally, we discuss the development prospects of this delivery system and challenges to its clinical translation. Biomimetic nanotherapy is believed to offer a new strategy for the treatment of IBD.

Phototherapy has emerged to eradicate recalcitrant bacteria without causing drug resistance, but it is often accompanied by considerable limitations owing to a high tolerance of recalcitrant bacteria to heat and oxidative damage, leading to low efficiency of monotherapy and unwanted side effects. Assuming that employing antimicrobial peptides (AMPs) to disrupt bacterial membranes could reduce bacterial tolerance, a multifunctional "on-demand" nanosystem based on zeolitic imidazolate framework-8 (ZIF-8) with metal ions for intrinsic antibacterial activity was constructed to potently kill methicillin-resistant (MRSA). Then, microneedles (MNs) were used to transdermally deliver the ZIF-8-based nanosystem for localized skin infection. After MNs insertion, the nanoplatform could specifically deliver the loaded therapeutic components to bacterial infection sites through employing hyaluronic acid (HA) as a capping agent, thus realizing the "on-demand" payload release triggered by excess hyaluronidase secreted by MRSA. The prepared nanosystem and MNs were confirmed to exert an amplified triple therapy originating from membranolytic effect, phototherapy, and ion therapy, thus displaying a powerful bactericidal and MRSA biofilm destruction ability. This intelligent antimicrobial strategy may bring a dawn of hope for eradicating multidrug-resistant bacteria and biofilms.

We combined carbon dioxide (CO)-responsive cytosine-containing rhodamine 6G (Cy-R6G) as a hydrophobic anticancer agent with hydrogen-bonded cytosine-functionalized polyethylene glycol (Cy-PEG) as a hydrophilic supramolecular carrier to construct a CO-responsive drug delivery system, with the aim of enhancing the responsiveness of the system to the tumor microenvironment and thus the overall effectiveness of anticancer therapy. Due to self-complementary hydrogen bonding interactions between cytosine units, Cy-R6G and Cy-PEG co-assemble in water to form spherical-like nanogels, with Cy-R6G effectively encapsulated within the nanogels. The nanogels exhibit several distinctive physical features, such as widely tunable nanogel size and drug loading capacity for Cy-R6G, intriguing fluorescence properties, high co-assembled structural stability in normal aqueous environments, enhanced anti-hemolytic characteristics, sensitive dual CO/pH-responsive behavior, and precise and easily controllable CO-induced release of Cy-R6G. Cytotoxicity assays clearly indicated that, due to the presence of cytosine receptors on the surface of cancer cells, Cy-R6G-loaded nanogels exert selective cytotoxicity against cancer cells in pristine culture medium, but do not affect the viability of normal cells. Surprisingly, in CO-rich culture medium, Cy-R6G-loaded nanogels exhibit a further significant enhancement in cytotoxicity against cancer cells, and remain non-cytotoxic to normal cells. More importantly, a series of experiments demonstrated that compared to pristine culture medium, CO-rich culture medium promotes more rapid selective internalization of Cy-R6G-loaded nanogels into cancer cells through cytosine-mediated macropinocytosis and thus accelerates the induction of apoptosis. Therefore, this newly developed system provides novel avenues for the development of highly effective CO-responsive drug delivery systems with potent anticancer capabilities.

Angiogenesis is essential for diabetic wound healing. Endothelial progenitor cell-derived extracellular vesicles (EPC-EVs) are known to promote wound healing by enhancing angiogenesis, while the low yield and lack of effective targeting strategies limit their therapeutic efficacy. Here, the biomimetic nanovesicles (NVs) prepared from EPC (EPC-NV) through an extrusion approach were reported, which functioned as EV mimetics to deliver contents from EPC to the wound. Besides, the cRGD peptide was coupled to the surface of EPC-NV (mEPC-NV) to achieve active endothelial cells (ECs)-targeting. Furthermore, we developed a dual hydrogel network by combining Fe@ Protocatechualdehyde (PA) complex-modified Acellular Dermal Matrix (ADM) with light-cured gelatin (GelMA), to enrich and sustainably release mEPC-NV. The hydrogel system with antioxidant and antibacterial properties also made up for the deficiency of mEPC-NV, reducing reactive oxygen species (ROS) and inhibiting infection in diabetic wound. Taken together, this study established a novel bioactive delivery system with angiogenesis, antioxidant and antibacterial activities, which might be a promising strategy for the treatment of diabetic wound.

Traumatic brain injury (TBI) can lead to severe neurotrauma, leading to long-term cognitive decline and even death. Massive neuronal loss and excessive neuroinflammation are critical issues in the treatment of secondary TBI. To tackle these challenges, we developed a GelMA and CSMA hydrogel loaded with Erythropoietin (EPO) and Interleukin-4 (IL-4), named GC/I/E. By directly loading the hydrogel with EPO, rapid neuroprotection and angiogenesis were achieved. Meanwhile, by loading Mesoporous silica nanoparticles (MSNs) with IL-4 (MSN@IL-4), sustained inflammation modulation during inflammation was attained. experiments demonstrated that GC/I/E hydrogel were biocompatible and could provide neuroprotection for HT22 cells in HO environment, regulate RAW264.7 polarization from M1 to M2 phenotype and promote HUVEC angiogenesis. experiments demonstrated that GC/I/E hydrogel reduced brain edema and Nissl body damage, inhibited inflammatory expression of G3-FFAP and neural scarring, improved microvascular and vascular function reconstruction, and facilitated neuronal and synaptogenesis, ultimately improving neurofunctional recovery in TBI. RNA sequencing results demonstrated that GC/I/E hydrogel treatment significantly correlated with the regulation of genes such as apoptosis, inflammation regulation, and neural regeneration. This bioactive hydrogel with neuroprotection, inflammation modulation and promotion of angiogenesis has great potential for TBI treatment.

The choice of suitable materials and effective structural design are crucial in influencing the therapeutic outcomes of bone tissue engineering scaffolds. This study introduces a controllable biodegradable composite scaffold composed of flat silkworm cocoon (FSC) and polylactic acid (PLA) as an innovative strategy for promoting bone healing in complex injuries. We focused on optimizing the scaffold's structural design, mechanical properties, and underlying mechanisms of osteogenesis. Initial experiments established the parameters for hot pressing the FSC, followed by mechanical performance tests to identify the optimal preparation conditions. Composite scaffolds incorporating PLA films were subsequently fabricated using these optimized parameters. The results indicate that the FSC/PLA composite scaffold exhibits outstanding biocompatibility, mechanical strength, and in vitro mineralization capabilities, alongside an appropriate degradation rate. Furthermore, the composite scaffolds demonstrated significant potential in promoting osteogenic differentiation and facilitating macrophage polarization toward an anti-inflammatory M2 phenotype. In vivo implantation of the scaffold in defective regions enhanced osteogenesis and mitigated inflammatory responses associated with degradation. This investigation presents an optimal composite scaffold that closely mimics the complex structure of bone, offering a novel approach to enhance bone regeneration and effectively address substantial bone defects.

Cardiovascular disease (CVD) ranks among the leading causes of morbidity and mortality globally, primarily due to arterial occlusive disease. Vascular bypass remains the cornerstone of treatment; however, many patients lack suitable autologous vessels (e.g., saphenous vein) for grafting. Tissue-engineered vascular grafts (TEVGs) provide a viable alternative capable of integrating, remodeling, and repairing host vessels, responding to mechanical and biochemical stimuli. Currently, preparation methods for TEVGs are mainly categorized into scaffold-free and scaffold-based approaches. Scaffold-free methods exhibit comparatively weaker mechanical properties and limited research progress, whereas scaffold-based approaches show more promising applications due to their superior mechanical properties and biocompatibility. This review examines current research progress in materials, fabrication processes, functionalized modifications, cell implantation, and animal and clinical experiments for scaffold-based preparation of TEVGs. By exploring current challenges and future perspectives in this field, we expect to provide new insights into TEVGs development and expedite their clinical applications.

Nucleus pulposus (NP) cells, situated at the core of intervertebral discs, have acclimated to a hypoxic environment, orchestrating the equilibrium of extracellular matrix metabolism (ECM) under the regulatory influence of hypoxia inducible factor-1α (HIF-1α). Neovascularization and increased oxygen content pose a threat, triggering ECM degradation and intervertebral disc degeneration (IVDD). To address this, our study devised an oxygen-controllable strategy, introducing laccase into an injectable and ultrasound-responsive gelatin/agarose hydrogel. Laccase-mediated reactions were employed to deplete oxygen, establishing a hypoxic microenvironment that upregulated HIF-1α expression. The activation of hypoxia-inducible factors significantly enhanced the expression of aggrecan and collagen II, concurrently suppressing Matrix metalloproteinases (MMP13) and A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS5) levels, thereby restoring the equilibrium of ECM metabolism. Simultaneously, the hydrogel facilitated the recruitment of stem cells into the NP through the controlled release of ATI2341, activating C-X-C chemokine receptor type 4 (CXCR4). Moreover, ultrasound amplification enhanced ATI2341 release, promoting the migration of NP stem cells. The hydrogel's efficacy in mitigating metabolic imbalances and inhibiting IVDD progression was substantiated in a rat puncture IVDD model through hydrogel injection into the discs. In conclusion, this hypoxia-inducible hydrogel, responsive to thermal stimuli from ultrasound, presents a promising avenue for IVDD treatment.

Chemokines are emerging as important targets for cancer immunotherapy due to their role in regulating immune cell migration and activation within the tumor microenvironment. Effective delivery and sustained presence of chemokines at the tumor site is essential for recruiting and activating immune cells to exert anti-tumor effects. In this study, we report a genetically engineered bacterial cell factory designed for the continuous production of chemokine CCL21 in a controlled manner. To decrease the formation of infusion bodies (IBs) in bacteria, we used thioredoxin (Trx) as the fusion partner and cloned at N-terminal of the target protein. The commonly used promoters, pT7-LacO, pBV220, and pDawn, were employed to explore the influence of various inducers on the expression of CCL21 in bacteria. The engineered bacteria were finally encapsulated within spherical gelatin methacryloyl (GelMA) microgels, which not only maintained bacterial viability but also prolonged their retention in the intestines of mice. As a result, the sustained presence and localized production of CCL21 led to effective suppression of tumor growth.

Intervertebral disc degeneration (IDD) is a common degenerative disease of the spine that has a significant impact on both society and human health. Many studies have confirmed that there is a close relationship between IDD and senescence and apoptosis, and autophagy can combat apoptosis and senescence. Spatholobi caulis (SC) is an herb that contains various active compounds that are effective in tissue repair and regeneration, but it has not been explored in field of IDD. In this study, it was first found that SC can boost autophagy and reduce the apoptosis and senescence of Nucleus pulposus cell (NPCs). However, our animal studies revealed limited absorption of SC. To improve the bioavailability and efficacy of SC, we developed a hydrogel incorporating quaternary ammonium chitosan (QCS) and oxidized starch (OST) as carriers for SC. The QCS-OST/SC hydrogel exhibits excellent compatibility with cells, can be easily injected, and can release SC durably. At the cellular level, the QCS-OST/SC hydrogel enhances cell viability, initiates autophagy and release of the extracellular matrix (ECM), and inhibits cellular senescence and apoptosis. The injection of the QCS-OST/SC hydrogel via microneedles (MNs) into discs had successfully diminished disc degeneration in rats, which shows that this hydrogel has broad potential in the treatment of IDD.

Spinal cord injury (SCI) results in severe neurological deficits due to disrupted neural pathways. While the spinal cord possesses limited self-repair capabilities, recent advancements in hydrogel-based therapies have shown promise. Polyphenol-based hydrogels, known for their neuroprotective properties, offer a suitable microenvironment for neural regeneration. In this study, a novel poly(lipoic acid)/poly(dopamine) adhesive hydrogel was developed as a versatile platform for delivering therapeutic agents. This hydrogel was loaded with methylcobalamin, a neurotrophic factor, and tellurium nanoenzymes, potent antioxidants. The nanoenzymes effectively mitigated oxidative stress and inflammation, while methylcobalamin promoted nerve regeneration. The combined therapeutic effects of the nanoenzymatic hydrogel demonstrated significant efficacy in repairing spinal cord injuries, highlighting its potential as a promising strategy for treating this debilitating condition.

Acute kidney injury (AKI) induced by cisplatin (DDP), which is accompanied with the generation of reactive oxygen species (ROS), is a severe side effect during treatment and restricts the application of DDP. In this study, we develop ultrasmall MnO nanozyme (UMON) with tumor microenvironment (TME) responsive ROS scavenging and generating as adjuvant to alleviate DDP induced AKI with improved efficacy. In kidney, UMON with superoxide dismutase and catalase activity acts as ROS scavenger to eliminate ROS generated by DDP, successfully protecting the renal cells/tissue and alleviating AKI during DDP treatment. Alternatively, UMON rapidly responses to the high GSH level in TME and release Mn in tumor. This unique feature endows it to generate hydroxyl radicals (∙OH) through a Fenton-like reaction and deplete GSH in tumor cell and tissue, achieving high efficient chemodynamic therapy (CDT). More importantly, the Mn successfully activates the cGAS-STING pathway, initiating the immune response and effectively inhibiting the tumor metastases. The synergistic CDT and immune therapy effectively improve the anti-tumor efficacy of DDP and . This study demonstrates that TME responsive ROS scavenger/generator shows the potential to reduce side effects of DDP while improve its therapeutic efficacy, providing a new avenue to achieve efficient chemotherapy and promoting the progress of clinical chemotherapy.

Myocardial infarction (MI) remains the leading cause of death related to cardiovascular diseases globally, presenting a significant clinical challenge due to the specificity of the lesion site and the limited proliferative capacity of cardiomyocytes (CMs) for repairing the infarcted myocardium. Extensive studies reported so far has focused on the utilization of hydrogel-based cardiac patches for MI treatment, highlighting their promising mechanical properties, conductivity, and ability to remodel the microenvironment post-repair. However, the majority of developed cardiac patches have been limited to the myocardial tissue surface via suturing or adhesive administration. Suturing inevitably leads to additional damage to the fragile myocardium, while uneven application of adhesives may result in patch displacement and compromised drug release. Based on these critical issues, we systematically summarize the advantages and drawbacks of using hydrogel patches for MI treatment with emphasis on elucidating various design strategies. Specifically, we first describe the changes in the pathological microenvironment following MI. Next, we discuss the biomimetic types of hydrogel patches, their functional design, and corresponding strategies for microenvironment adaptation, emphasizing adhesion mechanisms, wet adhesion design strategies, and fabrication techniques for hydrogel patches. Finally, we address the potential challenges and prospects of hydrogels as patches for MI therapy. The review is believed to provide theoretical guidance for the development of new therapeutic strategies for effectively MI treatment.

The skin is the body's primary immune barrier, defending it against pathogenic invasion. Skin injuries impose a significant physiological burden on patients, making effective wound management essential. Dressings are commonly employed in wound care, and electrospun nanofiber dressings are a research hotspot owing to their ease of fabrication, cost-effectiveness, and structural similarity to the extracellular matrix. Coaxial electrospinning offers considerable advantages in drug delivery, fiber structure transformation, and enhanced interaction with the host. These attributes make coaxial electrospun materials promising candidates for precision and personalized wound dressings in medical treatments. This review provides a comprehensive overview of wound healing and its influencing factors. It also outlines coaxial electrospinning's production principles and benefits in wound dressings. Guided by the factors affecting wound healing, coaxial electrospun nanofiber dressings have different application modalities. Furthermore, we discuss the current limitations and future directions for enhancing the current coaxial electrospun dressing technologies.

The management of diabetic wounds presents a considerable challenge within the realm of clinical practice. Cellular-derived nanoparticles, or extracellular vesicles (EV), generated by human adipose-derived stem cells (hASCs) have been investigated as promising candidates for the treatment of diabetic wounds. Nevertheless, limitations on the yield, as well as the qualitative angiogenic properties of the EV produced, have been a persistent issue. In this study, a novel approach involving the use of various cell culture morphologies, such as cell spheroids, on hASC was used to promote both EV yield and qualitative angiogenic properties for clinical use, with an emphasis on the in vivo angiogenic properties exhibited by the EV. Moreover, an increase in the secretion of the EV was confirmed after cell spheroid culture. Furthermore, microRNA(miRNA) analysis of the produced EVs indicated an increase in the presence of wound healing-associated miRNAs on the cell spheroid EV. Analysis of the effectiveness of the treated EVs in vitro indicated a significant promotion of the biological function of fibroblast and endothelial cells, cell migration, and cell proliferation post-cell spheroid EV application. Meanwhile, in vivo experiments on diabetic rats indicated a significant increase in collagen production, re-epithelization, and angiogenesis of the diabetic wound after EV administration. In this investigation, we posit that the use of cell spheroids for the culture of hASC represents a novel approach to enhance the substantial secretion of extracellular vesicles while increasing the angiogenic wound healing properties. This innovation holds promise for augmenting the therapeutic potential of EVs in diabetic wound healing, aligning with the exigencies of clinical applications for these nanoparticles.

Organ-on-a-chip, an in vitro biomimetic microsystem that enables precise regulation and real-time observation of the cell microenvironment, has the potential to become a powerful platform for recapitulating the real microenvironment of organs in vitro. Microenvironmental factors, such as living cells, three-dimensional (3D) culture, tissue-tissue interfaces, and biomechanical factors, are important cues in the construction of biomimetic microsystems. It is important to provide an appropriate 3D culture environment for living cells to grow. Fibers, particularly microfibers and nanofibers, can provide a suitable 3D culture environment for living cells via surface adhesion or internal loading. In addition, fibers can further expand their applications in tissue engineering and biomedical research by being assembled at a higher level in various ways to create functional 3D tissues or organs with more complex structures. The use of fiber to construct an organ-on-a-chip, whether as a 3D scaffold for cell culture or to more closely mimic real tissues/organs, will introduce new ideas and strategies for developing novel organ-on-a-chip systems. Based on this context, this review summarizes the research progress in the construction and applications of micro/nanofibers for organ-on-a-chip systems. It outlines the preparation methods and material selections for micro/nanofibers and provides a detailed overview of their respective strategies for cell 3D culture and organ-on-a-chip construction. This review also highlights the main research findings and applications of micro/nanofiber in this field, which have significant implications for future practice, and finally concludes by examining potential directions for future development.

Ion interference, including intracellular copper (Cu) overload, disrupts cellular homeostasis, triggers mitochondrial dysfunction, and activates cell-specific death channels, highlighting its significant potential in cancer therapy. Nevertheless, the insufficient intracellular Cu ions transported by existing Cu ionophores, which are small molecules with short blood half-lives, inevitably hamper the effectiveness of cuproptosis. Herein, the ESCu@HM nanoreactor, self-assembled from the integration of H-MnO nanoparticles with the Cu ionophore elesclomol (ES) and Cu, was fabricated to facilitate cuproptosis and further induce relevant immune responses. Specifically, the systemic circulation and tumoral accumulation of Cu, causing irreversible cuproptosis, work in conjunction with Mn, resulting in the repolarization of tumor-associated macrophages (TAMs) and amplification of the activation of the cGAS-STING pathway by damaged DNA fragments in the nucleus and mitochondria. This further stimulates antitumor immunity and ultimately reprograms the tumor microenvironment (TME) to inhibit tumor growth. Overall, ESCu@HM as a nanoreactor for cuproptosis and immunotherapy, not only improves the dual antitumor mechanism of ES and provides potential optimization for its clinical application, but also paves the way for innovative strategies for cuproptosis-mediated colorectal cancer (CRC) treatment.

Bacterial-infected wounds could cause delayed wound healing due to increased inflammation, especially wounds infected by drug-resistant bacteria remain a major clinical problem. However, traditional treatment strategies were gradually losing efficacy, such as the abuse of antibiotics leading to enhanced bacterial resistance. Therefore, there was an urgent need to develop an antibiotic-free multifunctional dressing for bacterially infected wound healing. This study demonstrated the preparation of a multifunctional injectable hydrogel and evaluated its efficacy in treating acute and infected wounds. The hydrogel was prepared by a one-step mixing method, and cross-linked by natural deep eutectic solvent (DES), polyvinyl alcohol (PVA), chitosan (CS), tannic acid (TA), and Cu through non-covalent interactions (hydrogen bonds and metal coordination bonds). PVA/CS/DES/CuTA hydrogel has multiple functional properties, including injectability, tissue adhesion, biocompatibility, hemostasis, broad-spectrum antibacterial, anti-inflammatory, and angiogenesis. Most importantly, in the -infected skin wound model, PVA/CS/DES/CuTA hydrogel could ultimately accelerate infected wound healing by killing bacteria, activating M2 polarization, inhibiting inflammation, and promoting angiogenesis. In summary, the PVA/CS/DES/CuTA hydrogel showed great potential as a wound dressing for bacterial infected wounds treatment in the clinic.

The evaluation of thyroid lesions through Fine-Needle Aspiration Biopsy (FNAB) is a common procedure that requires advanced hand manipulation skills. Conventional training models for this procedure lack essential features such as tactile sensation and the ability to repeat punctures similar to those of real organs. To improve the quality of training, we have developed a hydrogel thyroid model that possesses features such as high-water retention and self-healing properties. This model consists of polyvinyl alcohol (PVA), polyacrylic acid (PAA), and trehalose that enhance water retention. By utilizing indirect printing technology, this hydrogel-based thyroid model closely resembles those of porcine thyroid tissue in terms of compression modulus and friction coefficient, exhibiting exceptional conformability, flexibility, and a water retention rate of 94.7 % at 6 h. It also displays a thrust force range of 0-0.98 N during simulated puncture, closely approximating real FNAB operations. This model shows evidence that it effectively simulates thyroid tissue and can be utilized for repetitive FNAB training to enhance the proficiency of medical personnel. Our study focuses on introducing new possibilities for developing advanced materials training models to be utilized in the medical field.