[This corrects the article DOI: 10.1063/5.0280958.].

Myocardial infarction (MI) poses a severe threat to human life and health. During acute MI, persistent myocardial ischemia and hypoxia induce pathological alterations in the microenvironment. Traditional therapeutic approaches exhibit limited capacity for targeted modulation of this infarcted microenvironment. Consequently, developing therapeutic strategies capable of precisely responding to the pathological microenvironment holds significant importance. Hydrogels, as a class of polymeric biomaterials with excellent biocompatibility, can be engineered into intelligent responsive hydrogels by incorporating environmentally responsive functional groups or constructing intelligent network architectures. These hydrogels are designed to sense and respond to key features of the MI pathological microenvironment, such as temperature, pH, reactive oxygen species, and enzyme concentrations. This review systematically summarizes the design strategies and research advances in intelligent responsive hydrogels for MI therapy over recent years, focusing on their distinct functional capabilities: alleviating oxidative damage, suppressing excessive inflammatory responses, enabling precise drug delivery, and modulating immune activity. Although current research predominantly remains at the preclinical stage and faces numerous challenges, the convergence of materials science and biomedical engineering positions smart responsive hydrogels as promising candidates to deliver innovative solutions for the precise treatment of MI.

Evidence has shown that high-intensity laser therapy (HILT) may be beneficial for recovery after peripheral nerve injury (PNI). However, the optimized doses and effective mechanisms remain unclear. The present study sought to explore the effects of various doses of HILT on the recovery of nerve function in sciatic nerve injury (SNI) rats. The potential mechanism of action of HILT alleviating PNI was also assessed. Behavioral testing, polymerase chain reaction, immunoblotting, and immunofluorescence analyses were applied to explore whether HILT promotes the repair of injured nerves and its underlying mechanisms. SNI induces mechanical nociceptive hypersensitivity, disrupts sciatic nerve structure and function, causes gastrocnemius muscle atrophy, and increases oxidative stress and expression levels of inflammatory factors. HILT effectively ameliorated these SNI-induced alterations. Notably, the Bone Morphogenetic Protein 4 (BMP4)-SMAD Family Member 9 (Smad9) pathway mediates the therapeutic effects of HILT on SNI repair. These findings show for the first time that HILT stimulates the BMP4-Smad9 signaling pathway by increasing Smad9 expression to regulate inflammation and oxidative stress, which ultimately ameliorates SNI.

Growth factors (GFs) are potent regenerative proteins that modulate biological responses and stimulate tissue repair by activating cell signaling pathways to enhance proliferation, differentiation, and migration. However, the rapid degradation and diffusion characteristics of GFs necessitate the use of supraphysiological doses and/or frequent administrations to maintain therapeutic effects, which can result in reduced efficacy and an increased risk of adverse events. To address these challenges, novel GF delivery systems seek to preserve bioactivity and modulate GF release, ultimately promoting more effective tissue regeneration. Heparan sulfate (HS) is an essential regulator of GF activity, executing molecular recognition and information storage for controlling extracellular matrix remodeling and cellular behavior during tissue development. In this perspective, we summarize the diverse roles of HS in tissue repair, focusing on its interactions with GFs. These include protective functions, the tonic release of GFs, promoting the complexation of GFs with their cognate receptors, and enhancing the activation of intracellular signaling. Finally, we provide perspectives on using HS as a component of novel biomaterials and medical devices for improving tissue regeneration.

Innovative methods for finger gesture recognition have been an active research area, with surface electromyography (sEMG) emerging as a promising approach in human-machine interface applications, especially when visual imaging is impractical. However, sEMG-based gesture recognition is highly susceptible to movement artifacts, individual muscle activation, and changes in hand position, making dynamic gesture recognition challenging. While progress has been made in sEMG data collection and analysis, most studies focus on controlled, static hand positions, limiting real-world applicability. This study integrates a soft wearable sEMG sensor, a Video-Vision-Transform model, and motion sensor-based training to predict finger joint angles and recognize gestures across both static and dynamic hand positions. Despite inter-subject variability, results demonstrate differentiation of finger angles and gestures. For the highly performing subject, recognition accuracy reached 0.85 for static and 0.87 for dynamic settings. This work advances sEMG-based gesture recognition, indicating stable performance across tested static and dynamic conditions, suggesting potential suitability for natural and real-world applications.

Diagnosis of a glioblastoma (GBM) brain tumor is associated with very poor prognosis. Currently, few preclinical models used to identify new therapies address the soft brain tissue environment and GBM mechanoresponses, which are implicated in disease progression. Understanding the GBM biomechanical landscape is critical to deriving improved preclinical models and magnetic resonance elastography (MRE) holds promise to address this gap. Due to technical and feasibility issues for MRE of patient tumors at scale, most studies only report on small cohorts of patients, thus limiting the conclusions that may be drawn from individual studies. To thus gain a better overview, we have undertaken a systematic review and meta-analysis of the reported tissue viscoelastic property values from studies of both healthy brain and brain tumors, with a particular focus on delineating measurements relative to MRE transducer vibration frequency. Based on these analyses, healthy white matter consistently appears stiffer than gray matter. Further, analyses of pooled healthy brain tissue measurements vs human GBM suggested that, overall, the GBM has the same stiffness as the surrounding healthy tissue. This contrasted with mouse models of GBM, where the tumors appear softer than brain tissue. The limited number of studies of human GBM in situ is a caveat to these conclusions and MRE analyses of larger GBM patient cohorts are urgently needed. Meanwhile, the information from this analysis can be used to guide engineering of improved preclinical models with features that recapitulate the in vivo brain tissue environment.

Animal models, especially rodents, used to study neurodevelopment have significantly advanced our comprehension of cellular and molecular mechanisms. Nevertheless, differences in species-specific structures, gestation periods, and interneuronal connections limit animal models' ability to represent human neurodevelopment accurately. The unique characteristics of primate neural progenitor cells (NPCs) enable cortex expansion with gyrus formation, which does not occur in lissencephalic animals, like rodents. Therefore, there is a need for novel in vitro models using human cells that recapitulate the complexity of human brain development. Along with organoids, 3D bioprinting offers a platform for creating more complex in vitro models. We developed, extensively characterized, and successfully used a Geltrex™/GelMA hydrogel blend to bioprint human induced pluripotent stem cells-derived NPCs (hNPCs). We show that 3D bioprinted hNPCs can self-organize, revealing key features of a neurogenic niche, including proliferation, differentiation, and migration, remaining viable for over 110 days. Within the first 20 days, bioprinted constructs showed the formation of positive cell clusters for the neurogenic niche cell markers FABP7, NESTIN, and GFAP. Clusters were interconnected by process bundles supporting cell migration. The cells proliferated within the clusters, and over time, NPCs originated TUBB3+ neurons with long axonal tracts, prominent around the clusters. We propose this as a 4D model to study neurogenic niches' key cellular and molecular features in a 3D bioprinted scaffold, adding time as the fourth dimension. Neuronal maturation in this dynamic model recapitulates key neurogenic niche properties, making it suitable for neurodevelopmental disease modeling and drug screening.

Damage to the olfactory nerve, caused by aging, trauma, or neurological disorders, can lead to smell loss, negatively impacting quality of life, taste perception, safety, and emotional well-being. Currently, olfactory training, which involves exposure to aromatic odorants, is the most widely used treatment. While this method provides some benefit, it does not offer a fundamental cure. Developing an approach that directly stimulates the olfactory nerves to restore neural activity is critical for effectively addressing smell loss. This study investigates the effects of radiofrequency (RF) stimulation on the olfactory nerves in healthy individuals to evaluate its potential as a treatment for olfactory dysfunction. An RF antenna was positioned, and the specific absorption rate was verified using 3D modeling. The sensitivity of odor threshold tests with n-butanol and specific odors was assessed in a total of 28 healthy subjects, confirming olfactory nerve stimulation through electrobulbogram measurements. The average odor threshold for n-butanol in 23 subjects was 9.73 ± 2.45. RF stimulation on the olfactory nerve for 5 min at 10–20 W improved the odor threshold score to 15.88 ± 0.25, indicating enhanced sensitivity lasting up to one week. Electrical signals from olfactory nerves significantly increased after RF stimulation compared to pre-stimulation levels, consistent with results for natural odors like grapes and bananas. Unlike chemical-based treatments, RF stimulation avoids discomfort or dissipation of effects and provides sustained nerve activation. These findings demonstrate the potential of RF technology for olfactory training and as a novel treatment for olfactory dysfunction, as well as applications in maintaining odor sensitivity for professionals.

As the most common primary malignant bone tumor, osteosarcoma (OS) is characterized by drug resistance and poor prognosis, highlighting the urgent need for promising therapeutic agents. Formononetin (FMN), a natural product derived from Spatholobi Caulis, has been reported to possess anti-tumor properties. However, its role in OS has not yet been elucidated. In the present study, we established an OS patient-derived xenograft model to investigate the effects of FMN and the underlying mechanisms of its effects on OS. When FMN treatment was completed, bulk transcriptome sequencing was conducted, and the analyses were combined with OS single-cell RNA sequencing (scRNA-seq) data. Results indicated that GTSF1 was up-regulated in OS but down-regulated after FMN intervention, which may regulate the apoptosis of OS cells. Furthermore, the qRT–PCR and IHC results demonstrated that GTSF1 expression was significantly up-regulated in OS cells, whereas FMN expression was down-regulated both in vitro and in vivo. Moreover, in vitro experiments revealed that FMN effectively promoted apoptosis and suppressed the proliferation, migration, and invasion of OS cells. Therefore, this study demonstrated that FMN exerts anti-OS effects by down-regulating GTSF1 expression, thus effectively promoting the apoptosis and inhibiting the proliferation of OS cells, making FMN a promising anti-OS drug.

Spinal cord injury (SCI) severely disrupts the central nervous system, with neuropathic pain (NP) emerging as a prevalent and challenging complication, affecting approximately two-thirds of affected individuals. This study aims to explore the immune landscape and potential drug therapeutic targets associated with NP post-SCI using single-cell and bulk RNA sequencing. We identified 1050 differentially expressed genes enriched in cytokine interactions and inflammatory pathways, including key pain-related genes like Itgb2, Ccr5, Fcrg3, and Adora3, through weighted gene co-expression network analysis and immune infiltration analysis. Cell communication analysis revealed the pivotal role of the Ccl4-Ccr5 signaling axis in the interaction between macrophages and natural killer cell, thereby intensifying neuroinflammatory responses and aberrant nociceptive signaling, which may contribute to apoptosis after SCI. Molecular docking and molecular dynamics simulations showed that quercetin had stable binding with Ccr5 and identified potential amino acid binding sites TYR-108 and PHE-109. In vivo experiments demonstrated that Ccr5 inhibitors and quercetin effectively improved the Basso mouse scale and mechanical withdrawal threshold score, concurrently attenuating spinal tissue apoptosis. Therefore, we propose that quercetin and Ccr5 inhibitors could potentially treat NP post-SCI by inhibiting the Ccl4-Ccr5 pathway and reducing apoptosis, providing new treatment avenues.