Cardiovascular diseases have become one of the major threats to human health. There is an urgent clinical need for small-diameter vascular grafts to achieve long-term implantation in the body. In previous studies, some progress has been made, but the prognosis is still poor. Heparin (HEP) is an anticoagulant that is widely applied in the clinical field and commonly used for anticoagulation modification of biomaterials. However, there is an important problem: HEP has almost no direct inhibitory effect on platelet adhesion, which may become one of the potential dangers after graft implantation. In recent years, it has been found that calcification is also a key factor affecting the long-term patency of small-diameter vascular grafts, which is often ignored. Therefore, in this study, based on HEP, procyanidin (PC) was introduced to modify the thermoplastic polyurethane (TPU) grafts fabricated by electrospinning to enhance the anticoagulation and anticalcification properties simultaneously. To verify the effects of drug modification on the material, the physical and chemical characterization, biocompatibility experiments and effectiveness tests of this vascular graft were conducted. The results indicated that the HEP-PC grafts could not only inhibit the excessive proliferation of human umbilical artery smooth muscle cells to some extent but also have excellent hemocompatibility. Particularly, in vivo experiments showed that this graft also achieved dual anticoagulation and delayed the calcification after implantation. These results suggested that HEP-PC-modified TPU might be a promising candidate for inhibiting intimal hyperplasia and anticalcification of small-diameter grafts.

Mechanical stimulation as a form of physical therapy plays a crucial role in regulating cellular behavior and promoting tissue regeneration. It can influence cell proliferation, differentiation, migration and extracellular matrix deposition, thereby providing a powerful biophysical cue in regenerative medicine. The implementation of precisely controllable mechanical stimulation relies on efficient and reliable tool platforms that can deliver defined magnitudes, frequencies, directions and temporal patterns of force, while maintaining high reproducibility and safety in biological environments. For mechanical stimulation of cells and injured tissues, a variety of materials as well as devices with distinct force outputs, such as stretchable elastic substrates, microfluidic shear systems and mechano-active scaffolds have been designed to meet diverse experimental and therapeutic requirements. Moreover, functional materials integrated with magnetic, acoustic and optical modalities are also been developed to establish remote mechanical stimulation systems, enabling spatiotemporally programmable interventions even in deep or delicate tissues. This review summarizes recent advances of the in vitro and in vivo strategies that leverage mechanical stimulation in regenerative medicine, along with its regulatory effects on regenerative processes in neural, skeletal, muscular and other tissues. Finally, the major challenges and prospects regarding materials and devices for mechanical stimulation in tissue therapy are discussed.

Abstract Poly(N-isopropylacrylamide) (PNIPAM) hydrogels are potential wound dressings due to their lower critical solution temperature (LCST) of 32 °C, close to physiological temperature, enabling injectable or spreadable formulations that quickly form a gel on irregular wounds while withstanding tissue motion. These systems aim to balance skin-like mechanical integrity, strong dry and wet adhesion, and deliver stability after placement. This review summarizes the impact of the LCST driven phase transition on water content, pore structure, stiffness, and interfacial hydration and how these effects regulate adhesion strength and failure mode. It compares major mechanical reinforcement strategies in PNIPAM-based dressings including hybrid nanocomposites, double network (DN) architectures, dynamic or sacrificial crosslinking strategies that enhance toughness, stretchability, and recovery. It also describes multifunctional systems incorporating antibacterial activity, hemostasis, sensing, photothermal response, or controlled drug release with emphasis on their effect on mechanics and adhesion. Since adhesion in soft hydrogels is strongly correlated with viscoelastic behavior, the review identifies rheological measures (G′/G ̋ trends, shear thinning, yield behavior, and recovery) as measures of injectability and wet adhesion stability. Lastly, essential translational barriers are defined, including limited biodegradability, additive cytotoxicity, sterilization, durability in exudate and motions, and standardized testing and reporting to facilitate reliable comparison and clinical relevance.

Abstract Reactive oxygen species (ROS) play a significant role in regulating various signaling pathways and biochemical reactions within cells during their proliferation and differentiation. Nonetheless, when excessive ROS are accumulated within cells, they will cause severe damage to cellular components like DNA, proteins, and lipids. With advances in nanotechnology, “ROS storm” has become a promising multi-faceted therapeutic strategy for tumor treatment, whose mechanism mainly lies in inducing a massive ROS surge within tumors via synthesis optimization, the modulation of tumor adaptive responses, and overcoming inherent constraints of individual ROS, so as to exceed the fatal threshold, thereby leading to severe oxidative damage. Therefore, in this review we would like to focus on the specific strategies of engineered nanomaterials for triggering ROS storms in tumor tissues and the resultant effects, which have been primarily described in terms of augmenting substrate supply, inhibiting antioxidant systems, enhancing catalytic efficiency, enriching the diversity of reactive species, and intensifying targeting accumulation respectively. Moreover, the strong potential of combining this strategy with therapies such as immunotherapy has been demonstrated in various studies and constitutes a key focus of our discussion. At the end of the review, the future outlook and the remaining challenges when it comes to clinical application have also been discussed. This review is aimed at providing an overview of previous anti-cancer studies based on ROS storm, and shedding new light on this innovative strategy with fresh perspectives, thereby facilitating advances in cancer nanomedicine.

The regeneration of osteochondral defect in osteoarthritis (OA-OCD) remains a significant clinical challenge, frequently accompanied by synovial inflammation and persistent joint pain. Tissue engineering scaffolds show promising application prospects; however, due to their lack of bioactive molecules, they often fail to effectively regulate extracellular matrix remodeling and inflammatory responses, resulting in poor repair outcomes. In our previous study, we identified epimedin C (Epi C) as one of the most bioactive compounds from Xianlinggubao (XLGB) through 3D human osteoarthritic chondrocyte pellet cultures, demonstrating significant anti-inflammatory and anabolic effects. In this study, we developed a novel biphasic scaffold incorporating Epi C to enhance osteochondral regeneration in an OA-like microenvironment. The biphasic scaffold consists of a cartilage phase [PLGA (50:50)] and a subchondral bone phase [PLGA (75:25)/β-TCP], both with biomimetic pore sizes, porosity and mechanical properties, while the incorporation of Epi C did not compromise the scaffold’s structural integrity. In vitro degradation experiments revealed that the cartilage phase degraded rapidly, facilitating the prompt release of Epi C, while the subchondral bone phase exhibited slower degradation, allowing for sustained drug release over an extended duration. In a rat OA-OCD model, PTP@Epi C scaffold significantly promoted subchondral bone regeneration compared to the OA-OCD group and PTP group. Additionally, the PTP@Epi C scaffold effectively inhibited the expression of TNF-α in the synovial tissue, thereby alleviating synovitis. Transcriptomic analysis and in vitro experiments demonstrate that Epi C downregulates NLRP3 mRNA expression by inhibiting the phosphorylation of IκBα and p65, thereby preventing p65 nuclear translocation and reducing NF-κB transcriptional activity. This ultimately suppresses NLRP3 mRNA levels and decreases downstream IL-1β secretion. In summary, the PTP@Epi C scaffold significantly enhances the osteochondral regeneration and improves the synovial microenvironment through a layered controlled release of Epi C, providing a novel approach for the OA-OCD treatment.

Bone defects represent a significant clinical challenge, frequently resulting in nonunion and impaired function. Although autologous bone grafts are considered the gold standard owing to their excellent biocompatibility, their application is constrained by limited donor availability, thereby driving the need for alternative biomaterials. In this study, we report the synthesis of copper-aluminum layered double hydroxide (CuAl-LDH) nanosheets as a bioactive platform for bone regeneration. The nanosheets were systematically characterized using transmission electron microscopy, energy-dispersive spectroscopy and dynamic light scattering, confirming uniform morphology, precise elemental composition and colloidal stability. To enable localized therapeutic delivery, CuAl-LDH nanosheets were incorporated into gelatin methacryloyl (GelMA) hydrogels to form a nanocomposite hydrogel (Gel-CAL). Mechanical testing demonstrated that tuning the CuAl-LDH concentration (0.01–0.1 wt%) significantly enhanced the compressive modulus of the hydrogel, while rheological analysis revealed rapid light-induced gelation kinetics, making it suitable for minimally invasive, in situ implantation. The nanocomposite exhibited sustained release of Cu2+ ions over 40 days and displayed strong antibacterial activity against Escherichia coli. In vitro studies using rat bone marrow mesenchymal stem cells showed that Gel-CAL effectively reduced intracellular reactive oxygen species levels and upregulated key osteogenic markers, including alkaline phosphatase. In a rat subchondral bone defect model, micro-computed tomography and histological analyses at 5 weeks post-implantation revealed that Gel-CAL induced a significantly higher new bone volume fraction compared to GelMA alone. These results demonstrate that CuAl-LDH nanosheets serve as a multifunctional biomaterial that integrates mechanical reinforcement, antibacterial properties and osteogenic stimulation, offering a promising strategy for bone regeneration.

[This corrects the article DOI: 10.1093/rb/rbaf003.].

The local stiffness of brain tissues increases in pathological states, and then, drives microglial cells to migrate towards stiffer areas for their functioning, but the underlying mechanism is still unclear. Herein, we investigated the role and mechanism of the mechanosensitive Piezo1 channel in matrix stiffness regulation of microglial cell migration using BV2 microglial cell line and mouse primary microglial cells growing on soft (500 Pa) and stiff (20 kPa) polyacrylamide (PA) hydrogels. Compared with soft substrates, stiff substrates promoted cell migration, upregulated the Piezo1 expression, raised intracellular Ca2+ concentration ([Ca2+]i) and favored F-actin reassembly. Cell migration and F-actin assembly were suppressed by inhibiting the Piezo1 channel, reducing the [Ca2+]i or inhibiting PI3K/AKT. In addition, stiff substrates induced AKT activation that was reversed by blocking the Piezo1 channel or preventing an increase in [Ca2+]i. Finally, stiff substrates induced a Piezo1-, Ca2+- and AKT-dependent decrease in the phosphorylation level of cofilin, which promotes cofilin severing F-actin, increases G-actin levels and further enhances F-actin reassembly, thereby promoting microglial cell migration. Collectively, our study has revealed that stiff matrix regulates drives microglial cell migration through the Piezo1/Ca2+/AKT/cofilin signaling axis-regulated F-actin reassembly. Our findings provide new insights into the mechanisms underlying tissue stiffness regulation of microglial cells occurring in neurological disorders.

The key obstacle to functional recovery after spinal cord injury (SCI) is the imbalance of the oxidative stress microenvironment in the injured area. Traditional drug therapies have limitations in regulating this environment and eliminating the excessive accumulation of reactive oxygen species (ROS) is crucial. In this study, an environmentally friendly and economical recombinant nanoenzyme (LA-HMPB) was successfully constructed, which achieves delivery to the SCI injury site and enhances the therapeutic capacity of lipoic acid (LA). This nanoenzyme alleviates oxidative stress through the Keap1/Nrf2 pathway, thereby promoting functional recovery after SCI. The research found that HMPB not only serves as a carrier but also enhances the antioxidant stress capacity of LA. After administration, LA-HMPB can distribute to the SCI site and exert its effects. It has been confirmed that this formulation reduces oxidative stress levels by regulating the Keap1/Nrf2 pathway, thereby promoting functional recovery. This natural nano-drug delivery platform strategy opens up broad prospects for the clinical treatment of SCI and provides a useful reference for the research on antioxidant therapy for other neurological diseases.

Radiotherapy improves the survival and life quality of individuals diagnosed with locally advanced or terminal pancreatic ductal adenocarcinoma (PDAC). Nevertheless, the ubiquitous of radioresistance resulted in ineffective outcome, which commonly observed the recurrence and malignant progression within the radiation target area. Our clinical observation has shown that PDAC cells resident in rigid tumor niche, therefore, to illuminate the underlying mechanism from the biomechanical perspective is of significant importance. To this end, PDAC models with tunable mechanical properties were constructed through 3D-bioprinted gelatin methacryloyl (GelMA) hydrogel, which enabled the precise manipulation of cellular behavior under physiological stiffness scopes. The effect of matrix stiffness on radiation tolerance of PDAC cells subjected to distinct X-ray radiation was assessed, and the results validated that stiff matrix promoted radioresistance. To elucidate the in-depth mechanism underlying this phenomenon, enrichment analysis was performed on DEGs between soft and stiff groups treated with 4 Gy X-ray radiation. The results showcased that glycolysis process was prominent enriched, further experiment demonstrated that matrix stiffness promoted the glycolysis level and lactate accumulation. The stiff group reinforced histone H3 lysine 18 lactylation level, and the inhibition of histone lactylation efficiently suppressed PDAC radioresistance. shRAD51 assay corroborated that H3K18 lactylation-driven RAD51 transcriptional activation, which established a causal link to radioresistance. Overall, our research shed light on the matrix stiffness mediated histone lactylation, which exerted essential role in PDAC radioresistance and provided insight into future radiotherapy from the perspective of biomechanics.