Spinal cord injury (SCI) leads to high rates of central nervous system impairment and imposes a significant treatment burden, highlighting the need for effective repair strategies. Bioscaffolds are considered to be multifunctional materials composed of bioactive polymers and signaling molecules, showing potential comparable to tissue engineering approaches utilizing exogenous stem cells. These bioscaffolds, which act as biological frameworks, can modulate intrinsic neuronal regeneration and the external microenvironment to facilitate SCI repair. This review explores the current status and future prospects of three-dimensional bioscaffolds for SCI repair, covering the pathophysiology of spinal cord injury, associated repair mechanisms, and key bioscaffold properties influencing repair efficiency. Notably, the review highlights new insights into the use of therapeutic bioscaffolds to promote endogenous stem cell differentiation, enhance axon growth, regulate the injury microenvironment, and support SCI repair. Finally, expert opinions are discussed, summarizing design principles for effective SCI-repair bioscaffolds and underscoring their significant potential for clinical applications.

Leveraging the traditional medicinal properties of the intestinal meridian herb Coptis chinensis (CC), CC carbon dots nanozymes (CCzymes) are developed for the treatment of ulcerative colitis (UC). The CC precursors provide functional fragments and oxygenated functional groups that endow CCzymes with pharmacological activity and potent scavenging ability of free radicals. Targeting UC, CCzymes can effectively promote the restoration of the intestinal microenvironment. CCzymes inhibit the secretion of pro-inflammatory cytokines downstream of the MAPK and PI3K-Akt signaling pathways by suppressing the expression of the gene encoding the receptor tyrosine kinase protein (Kit). At the same time, CCzymes inhibited the HIF-1 and JAK-STAT signaling pathways, which in turn inhibited M1-type polarization of macrophages. In addition, CCzymes selectively inhibit pathogenic bacteria while promoting the growth of beneficial microbiota, thus achieving a balanced gut microbiota. Importantly, CCzymes also increased the levels of bile acids and indole derivatives, thereby contributing to the restoration of intestinal barrier integrity. This study provides a novel approach to harness the therapeutic potential of herbal nano-enzymes, offering a powerful strategy for treating inflammatory diseases through targeted antioxidant therapy. Targeting UC, CCzymes can be effective in treating inflammatory diseases.

Cancer is still a serious clinical concern, and current therapy is ineffective due to the complex tumor microenvironment (TME). Thus, TME targeting has gained recognition as a significant therapeutic target in cancer therapy. Among these, cold atmospheric plasma (CAP) has been proposed as an emerging and novel cancer treatment owing to its unique characteristics of non-invasive nature and selective tumor cell killing. The current investigation reveals CAP as an effective strategy for TME modulation and tumor eradication, emphasizing its potential to enhance antitumor responses. This review explores the therapeutic potential of CAP in cancer treatment, with a particular focus on its impact on the TME and the underlying mechanisms of tumor cell death. Initially, the review provides a comprehensive overview of the TME and underscores its critical role in cancer progression and treatment responsiveness. It then examines the efficacy of CAP across various in vitro and in vivo tumor models, highlighting its modulatory effects on key components of the TME, including immune cells, stromal cells, and cancer physiological hallmarks such as immune suppression, hypoxia, acidosis, angiogenesis, and metabolism. Furthermore, the review synthesizes evidence on the diverse mechanisms of CAP-induced tumor cell death, including apoptosis, pyroptosis, ferroptosis, autophagy, and necrosis. Together, findings from a wide range of experimental studies demonstrate the promise of CAP as a selective and safe antitumor agent, capable of reprogramming the TME and inducing numerous forms of cancer cell death. In addition, the review addresses current challenges and future directions for CAP and stresses the necessity of protocol standardization, large-scale experimental validation, and rigorous safety evaluation before clinical implementation. Finally, the review anticipates CAP as a revolutionary tool in cancer care, offering hope for improved therapeutic efficacy and a paradigm shift in cancer treatment.

Fiber-type soft bioelectronics are revolutionizing wearable and implantable healthcare technologies by addressing critical clinical challenges, particularly minimizing the mismatch in mechanical stiffness between bioelectronics and biological tissues. These devices can seamlessly integrate with dynamic in vivo environments. Their inherent mechanical flexibility and structural adaptability enable applications in both confined sensitive regions and expansive highly mobile areas of the body. Beyond adaptability, fiber-type soft bioelectronics offer multifunctionality, enabling real-time biological signal acquisition, targeted drug delivery, and localized electrical stimulation. Moreover, fabric-based designs offer excellent conformability, making them suitable for long-term monitoring of physical, electrochemical, and electrophysiological signals. This article presents a comprehensive review on fiber-type soft bioelectronics technologies, with a focus on their wearable and implantable applications in healthcare. First, the fundamental requirements for these devices are outlined, describing the foundation for their design and functional integration. Technological advancements that fulfill those requirements are described based on actual examples. The review also examines the materials used for the fibers, highlighting their mechanical, electrical, and biocompatible properties. Next, strategies for fiber fabrication are discussed, including methods for transforming fibers into fabrics. Finally, recent breakthroughs in the applications of fiber- and fabric-type soft bioelectronics in health monitoring and therapeutic interventions are explored.

Central nervous system (CNS) injury can cause devastating neurological dysfunction in patients, permanently impairing their ability to take care of themselves and reducing their quality of life. At present, neural tissue engineering is the most promising way to treat this disease. However, there are still many challenges and obstacles in the process of correctly structuring tissue engineering. The successful development of tissue engineering relies on three key components: biological scaffold materials, seed cells, and various growth factors. In summary, this review provides a systematic analysis of scaffold materials differentiation strategies for inducing diverse stem cells into neuro-like cells. The synthesized findings not only accelerate regenerative medicine approaches but also provide the critical solutions for CNS injury treatment and advance therapeutic development, offering important references for future research and clinical translation.

Liposomes have emerged as the most clinically successful nanocarriers with good biocompatibility, low immunogenicity, and facile modification potential. However, their widespread application is limited by challenges associated with suboptimal drug release kinetics and poor bioavailability under complex physiological conditions. These limitations stem from the dual paradox of maintaining circulatory stability while enabling rapid drug release at target sites. Engineering of stimulus-responsive liposomal systems has been identified as a promising strategy for mitigating these biomedical delivery challenges. Such systems are designed to achieve spatiotemporally controlled drug release and nanomedicine in response to specific endogenous or exogenous stimulus, thereby enhancing therapeutic efficacy while minimizing systemic toxicity. A comprehensive understanding of the design principles and release mechanisms governing stimulus-responsive liposomes is essential for the rational development of advanced drug delivery systems. Therefore, this review systematically examines the design strategies for precise, stimulus-triggered drug release through a detailed analysis of the effects of liposome structure and composition on drug release, with particular emphasis on lipid component engineering for controlled release. Furthermore, it explores functionalization strategies, focusing on chemical modification approaches for stimulus-responsive behavior. The component-responsive design and functional modification strategies discussed herein provide a systematic framework for liposome research. Meanwhile, the fundamental understanding of stimulus-responsive liposomes is significantly advanced, thereby facilitating the development of more efficient and precise drug delivery and nanomedicine.

Mitochondrial dysfunction is linked to various diseases, such as ischemic syndrome and type 2 diabetes, primarily due to insufficient energy supply caused by low adenosine triphosphate levels. Mitochondrial transplantation therapy is an emerging therapeutic strategy that can supplement the respiratory capacity of damaged mitochondria, thereby addressing mitochondrial disorders at their root. However, poor viability after isolation from cells, difficulties in targeting delivery in vivo, and low cellular internalization efficiency constitute the major challenges for the clinical translation of mitochondrial transplantation. The integration of advanced biomaterial design may hold the key to address these issues and improve the therapeutic efficacy of mitochondrial transplantation. In this review, we summarize recent advancements in biomaterial-assisted mitochondrial transplantation by protecting mitochondria during delivery, improving the targeting efficiency in vivo, and facilitating mitochondrial internalization. We also emphasize the importance of synergistic therapy of mitochondrial transplantation with other therapies. Finally, we discuss current issues and potential future directions of biomaterial-assisted mitochondrial transplantation therapy, aiming to further promote its clinical translation.

As the demand for personalized health monitoring continues to rise, wearable electrochemical biosensors have attracted considerable attention owing to their superior performance. Two-dimensional (2D) nanomaterials, with their unique layered structure, high specific surface area, and exceptional electrical conductivity, demonstrate substantial potential in biosensing applications. The incorporation of 2D nanomaterials enhances sensor sensitivity, facilitates electron transfer, reduces the detection limit, and improves the ability to detect metabolites at low concentrations. Initially, this review outlines the properties of 2D nanomaterials, and then introduces the synergistic effects of composite materials that combine 2D nanomaterials with different materials to enhance biosensing performance. Subsequently, this paper offers an in-depth discussion of the working principles and various sensing mechanisms of electrochemical biosensors. Based on this foundation, this paper highlights the applications of 2D nanomaterials in detecting biomarkers in human body fluids, including sweat, tears, saliva, and interstitial fluid. Finally, the review analyzes the challenges associated with integrating 2D nanomaterials into wearable biosensors and explores the prospective advancements of these materials within the domain of wearable biosensing.

Immunotherapy has emerged as a transformative paradigm in tumor therapy, but its clinical potential remains limited by the immunosuppressive tumor microenvironment driven by dysregulated tumor metabolism. Aerobic glycolysis, a hallmark of abnormal tumor metabolism, not only fuels tumor proliferation but also reshapes the tumor microenvironment through lactate accumulation, hypoxia, and competitive glucose consumption. Recent advances in nanomedicine offer innovative strategies to reprogram tumor glycolysis for enhanced immunotherapy, achieved through precision targeting of pivotal nodes of glycolysis pathways, including glucose transport, enzymatic activity, and lactate consumption. This review systematically summarizes cutting-edge advances in glycolysis-rewiring nanomedicines, emphasizing their mechanisms in reversing immunosuppression and reinvigorating antitumor immune responses. Challenges in clinical translation and future directions for designing multifunctional metabolic-immune modulators are also critically discussed.

Neurodegenerative diseases (NDs) are a major cause of disability and the second leading cause of death worldwide. The progression of NDs is intricately linked to the disruption of immune homeostasis, which is characterized by excessive activation and infiltration of immune cells. Recent studies have uncovered the potential of nanomaterials (NMs) with immunomodulatory capabilities to effectively manage neuroinflammation and slow the progress of NDs. The review begins by elucidating the mechanisms through which NMs modulate innate and adaptive immune responses in the context of NDs. These mechanisms encompass the dampening of innate immune cell activation, particularly microglia and astrocytes, and the restriction of peripheral adaptive immune cell infiltration into the central nervous system (CNS). By doing so, NMs can alleviate neuroinflammation and promote the repair of damage induced by NDs. The review emphasizes the application of stimulus-responsive NMs for targeted immunomodulation within the CNS. Moreover, it discusses strategies to enhance NM targeting and develop of NM-based active immunotherapies as prospective therapeutic approaches for clinical application. Understanding the mechanisms and applications of NMs is pivotal for unlocking their full potential in immunomodulatory strategies. This knowledge will lay the foundation for novel therapies addressing the unmet clinical needs of NDs.

Improving oral peptide drug delivery is a longstanding pharmaceutical goal due to significant advantages in patient compliance and clinical versatility. However, despite extensive optimization of chemical permeation enhancers, orally delivered peptides such as semaglutide and octreotide remain limited by bioavailabilities below 1%, suggesting that critical determinants of gastrointestinal absorption have been inadequately addressed. In particular, mechanical forces generated by peristalsis and intimate dosage form–epithelium interactions, although influential for drug transport, have remained largely unexploited in oral drug delivery. Here we introduce a mechanobiological permeation-enhancement approach, leveraging microtopography to amplify mechanical stimuli, thus transiently modulating epithelial permeability through Piezo1 activation. Experiments employing magnetic microbeads and rose-petal-templated micropatterned films demonstrated that increased surface roughness correlates quantitatively with enhanced paracellular permeability in Caco-2 monolayers. Mechanistic studies using calcium imaging, selective inhibitors, and transcriptomics confirmed that microtopography-activated Piezo1 channels drive sustained intracellular Ca²⁺ influx and cytoskeletal remodeling, while finite-element modeling and ex vivo electron microscopy revealed mechanically induced transient intercellular gap formation. Importantly, integrating micropatterned films into oral enteric capsules in beagle dogs improved octreotide bioavailability by three-fold relative to the Food and Drug Administration approved formulations containing high-dose sodium caprate. These results establish microtopography-driven functional modulation of tight junctions as a safe, effective, and broadly applicable route to improve oral macromolecule absorption, offering a robust new framework to integrate physical enhancement strategies alongside traditional chemical excipients in advanced pharmaceutical formulations.

Constructing in situ tissue engineered heart valves based on xenogeneic decellularized heart valves (DHVs) is a promising strategy for heart valve regeneration. However, the inflammation triggered by foreign body responses results in maladaptive matrix remodeling and compromised mechanical support. Given the critical role of macrophages (Møs) in regulating several homeostasis to relieve xenogeneic rejection and promote tissue regeneration, folic acid modified cerium ions-tannic acid metal-polyphenol framework nanoparticles (FCT NPs) have been synthesized via a green coordination method and then loaded onto thiolated DHVs to reprogram macrophage phenotype. FCT NPs, with multiple enzyme-mimicking activity, biodegradability and biocompatibility, moderately scavenge various reactive oxygen species in M1 Møs, reprogramming them to increase the M2 phenotype. This reduces inflammatory factors levels and promotes secretion of anti-inflammatory and pro-regenerative cytokines, enabling elimination of inflammation and promotion of adaptive matrix remodeling. In vitro studies show that FCT-loaded DHVs (FCT@DHVs) exhibit excellent immunomodulatory capability, mechanical properties, hemocompatibility, and cytocompatibility. Rat implantation models reveal that FCT@DHVs achieve re-endothelialization and adaptive matrix remodeling via immunomodulation. They also exhibit excellent hemodynamics, hemocompatibility, histocompatibility, anti-calcification and mechanical support. Notably, M2 Møs numbers decrease with scaffold degradation, indicating self-adaptive immunomodulation. This strategy offers a promising approach for in situ heart valve regeneration based on xenogeneic DHVs.

Despite momentous divergence from oceanic origin, human beings and marine organisms exhibit elemental homology through silicon utilization. Notably, silicon serves as a critical constituent in multiple biomedical processes. Marine biosilicon, an abundant yet underutilized class of siliceous materials, represents a frontier in green and sustainable biomedical development. Enormous interest is garnered by the pursuit of intricate inorganic structures with superior properties involving hierarchical structure, mechanical performance, surface chemical activity, autofluorescent pigment, and intrinsic biosafety. These attractive features drive marine siliceous organisms toward widespread availability in diverse biomedical fields. Current challenges are thorough comparison of biogenic sources, scalable biomanufacturing, and long-term metabolism elucidation during biomedical translations. In this review, a brief overview of marine biosilicon sources is initially clarified. Advancements of engineered marine biosilicon are discussed with improved physicochemical attributes ranging from innovative strategies for tuning the sizes, surfaces, mechanics, and biosensors to fabricating sophisticated complex architectures through pioneering biofabrication designs. Advanced applications are comprehensively summarized on tissue engineering, aesthetic medicine, hemostasis, drug delivery, biosensing and bioimaging, tumor therapeutics as well as wearable devices. Further initiatives and perspectives are extensively delineated. As the first systematic assessment of marine biosilicon materials, this review offers a state-of-the-art framework and theoretical groundwork of biosilicon harnessing for sustainable biomedical applications. It endeavors to propel biosilicified resources and convert the biosiliceous gifts from marine sources to clinical biomedicines that benefit humanity.

This study aimed to investigate the role of force stimulation in promoting peripheral nerve regeneration and to elucidate the underlying mechanisms by which it enhances nerve repair. We developed two distinct force stimulation devices for in vivo and in vitro experiments. The in vivo device applied tensile stress to the sciatic nerve of mice, whereas the in vitro device used acoustic surface wave (SAW) actuators to apply fluid shear stress to dorsal root ganglion (DRG) neurons. We evaluated the effects of these mechanical forces on axonal regeneration, mitochondrial biogenesis, and adenosine triphosphate (ATP) production. In vivo experiments demonstrated that controlled mechanical stretching significantly improved axonal regeneration and functional recovery compared to autologous nerve grafting. Mechanical stretching facilitated myelin reformation and angiogenesis, providing a favorable environment for axonal growth. In vitro studies revealed that fluid shear stress increased mitochondrial density and ATP production in DRG neurons by promoting mitochondrial biogenesis through the activation of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α). In conclusion, tensile stress and fluid shear stress positively impact peripheral nerve repair and regeneration. Our findings suggest that mechanical forces can enhance the body's natural nerve repair mechanisms by restoring cellular energy and promoting axonal regeneration. These results have significant implications for the development of novel therapeutic strategies for peripheral nerve injuries and diseases.

The major issue of bioresorbable polymer vascular stents (BRPSs) is their insufficient radial capacity relative to metal stents. As a result, BRPSs are always designed with a larger thickness. However, the thicker struts substantially increase the risk of adverse events. Therefore, the clinical demand for thinner BRPSs is becoming increasingly urgent. In this study, we built on our previous research to develop BRPSs with only 100 μm thickness. Through in vitro experiments and numerical simulations, we evaluated the compression, expansion, vessel dilation processes, and hemodynamics of thinner BRPSs. We also validated the feasibility and benefits by in vivo experiments. The results demonstrated that during compression, expansion, and vessel dilation, the thinner BRPSs maintained sufficient Radial strength (RS) and decreased residual stress and plastic strain. They also mitigated intima damage, the recirculation region, and low wall shear stress distribution induced by stent implantation. In vivo experiments showed that thinner BRPSs effectively alleviated concerns related to thicker BRPSs, such as intimal hyperplasia, inflammatory response, and delayed endothelialization. In conclusion, the thinner BRPSs with 100 μm thickness in this study maintain adequate RS and reduce the risks of thicker stents, thereby exhibiting the potential for clinical application.

Polyurethane thermogels are attractive materials for biomedical applications due to their reversible temperature-controlled gelation that allows for in situ gelation at physiological temperatures. However, traditional thermogels are limited by their lack of ionizable groups, rendering them electroneutral. Herein, pendant amine groups were incorporated into amphiphilic polyurethane copolymers to obtain cationic polyelectrolyte thermogels. Polyurethane thermogels, unlike other cationic thermogels, have greater control over functional group density, enabling customization of charge density and resulting properties. This study elucidates the influence of cationic charges on their self-assembly and thermogelling properties. Notably, thermogels with greater cationic group density exhibit amplified pH responsiveness, enabling the material's pH sensitivity to be tailored. These findings provide critical insights into the hierarchical self-assembly mechanism, which dictates the thermogelling behavior and properties of cationic, amphiphilic copolymers, offering a deeper molecular understanding necessary for designing polyelectrolyte thermogels for specific biomedical applications.

Magnetic resonance imaging (MRI) techniques are essential for the diagnosis of hepatocellular carcinoma (HCC) and the development of precise treatment strategies. Multifunctional diagnostic agents integrating MRI capabilities have attracted considerable interest in precision oncology. In this study, a biomimetic nanoparticle (HAMM NPs) is engineered through the synthesis of Mn²⁺-doped mesoporous polydopamine (Mn-MPDA) as a drug carrier, followed by loading the hydrophilic sonosensitizer artesunate (ART) and coating with Hepa1-6 cell membranes. The resulting Hepa1-6@ART@Mn-MPDA nanoparticles (HAMM NPs) exhibit enhanced tumor accumulation owing to the homologous targeting capability conferred by the Hepa1-6 cell membrane. Under the acidic conditions of the tumor microenvironment, HAMM NPs undergo pH-triggered release of Mn²⁺ and ART. HAMM NPs exhibit excellent T₁/T₂ dual-modality MRI capability enabling precise liver cancer imaging and MRI-guided sonodynamic therapy (SDT). Upon ultrasound activation, ART generates cytotoxic reactive oxygen species in an oxygen-independent manner, which synergizes with Mn²⁺-mediated chemodynamic therapy via Fenton-like reactions. In both subcutaneous and orthotopic HCC models, HAMM NPs effectively inhibit tumor growth. This strategy overcomes the limitations of conventional SDT in hypoxic tumors, offering a promising approach for imaging-guided combination therapy against deep-seated tumors.

Acute kidney injury (AKI) is a severe disease driven by a vicious cycle of tubular damage, oxidative stress, and inflammation, yet current therapies remain limited by poor targeting, short bioavailability, and inability to synergistically regulate multiple pathological pathways. To address this, we develop multifunctional nano-networks (NNWs) through reaction-induced self-assembly of spermidine, epigallocatechin gallate, 2-formylphenylboronic acid, and deferoxamine via dynamic iminoboronate bonds. These NNWs exploit the oxidative AKI microenvironment to trigger disintegration, thereby enabling the site-specific release of therapeutic agents. Deferoxamine and epigallocatechin gallate chelate excess iron to suppress ferroptosis-associated apoptosis, while epigallocatechin gallate and spermidine synergistically mitigate oxidative stress and inflammation through reactive oxygen species scavenging, autophagy promotion, and cytokine inhibition. NNWs overcome the limitations of single-drug therapy or physically combined drug therapy by integrating targeted delivery, controlled release, and multi-pathway modulation, thereby disrupting the self-perpetuating injury cycle. In vitro and in vivo evaluations demonstrated enhanced renal accumulation and superior efficacy in alleviating AKI pathology. This platform provides a promising strategy for spatiotemporally coordinated AKI treatment, offering a blueprint for combinational nanotherapies in complex disease settings.

Cell membrane-coated nanoparticles (CM-NPs) are emerging as immune-intelligent nanoplatforms capable of integrating precise tumor targeting with immunological functionality. By harnessing the native surface architecture of donor membranes—particularly from cancer or immune cells—CM-NPs achieve immune evasion, homotypic recognition, and enhanced intratumoral retention. Beyond passive delivery, these constructs can promote antigen cross-presentation and T-cell priming, rendering them especially effective in immune-excluded or antigen-scarce tumors. Precision functionalization strategies, including aptamer-guided targeting, peptide-mediated infiltration, and magnetically navigable systems, further extend their therapeutic reach. A transformative advance lies in the use of autologous tumor-derived membranes, preserving patient-specific antigenicity and glycosylation profiles vital for adaptive immune engagement. Recent innovations in synthetic biology now enable programmable membrane design, supporting site-specific ligand attachment while maintaining immune stealth. Although challenges remain—ranging from membrane orientation fidelity to GMP-scale manufacturing—advances in microfluidics, quality control analytics, and real-time biomanufacturing are narrowing the translational gap. Together, CM-NPs represent a modular, adaptive therapeutic paradigm uniquely suited to align with the immunogenomic complexity of cancer, offering a pathway toward truly personalized and responsive immunotherapy.

Organic field-effect transistor (OFET)-based biosensors are promising for wearable technology due to their good flexibility and low-cost fabrication. However, their susceptibility to signal drift from mechanical stress and environmental factors like temperature has been a major limitation. In this Commentary, we highlight a novel strategy that fundamentally redesigns the OFET biosensing circuit to eliminate the drifts.