Significance: The mechanisms underlying degradation of biological cells due to mechanical fatigue are not well understood. Specifically, detrimental effects of fatigue on properties and homeostasis of human red blood cells (RBCs), as they repeatedly deform while traversing microvasculature, have remained largely unexplored. We present a general microfluidics method that incorporates amplitude-modulated electrodeformation to induce static and cyclic mechanical deformation of RBCs. Fatigue of RBCs leads to significantly greater loss of membrane deformability, compared to static deformation under the same maximum load and maximum-load duration. These findings establish unique effects of cyclic mechanical deformation on the properties and function of biological cells. Our work provides a means to assess the mechanical integrity and fatigue damage of RBCs in blood circulation.

Cell-based immuno-biosensors are novel platforms for studying immune responses of biological cells, with real-time insights more similar to physiological and pathological conditions. These systems utilize living immune cells as their main components, enabling them to detect disease-related biomarkers and cellular traits in a way that is often highly sensitive and label-free. Integration with microfluidics and organ-on-chip technologies has facilitated precise manipulational control over the cellular microenvironment. Not only has this resulted in high-throughput screening, but it also enabled smaller, more portable systems which can be used at the point of care. In this work, we review the recent advance in microfluidic cell-based immuno-biosensing associated with immune cells such as neutrophils, macrophages, T cell and dendrite cells. Some of the exciting developments include fusion with methods such as advanced imaging, electrical impedance sensing and application of machine learning to phenotyping. We will also elaborate on the issues related to the standardization of these systems, cell heterogeneity, and the challenges for translating these technologies for clinical application. Taken together, such integrated platforms have potential to fill the gap left in-between cellular immunology with biosensor engineering.

There exists a bidirectional interaction between cells and the surrounding extracellular matrix (ECM), driving increasingly stringent requirements for biomimetic matrices in the field of tissue engineering (Liu et al.). However, conventional static cross-linked hydrogels face significant application bottlenecks due to their insufficient mechanical properties, lack of selfhealing capability, and poor adaptability to dynamic biological environments. These materials struggle to precisely regulate degradation rates and exhibit low loading efficiency for bioactive molecules, which limits their broader application in precision medicine. To overcome these limitations, researchers have turned their attention to glycopeptide hydrogels-a novel class of multifunctional biomaterials constructed from polysaccharides and peptide chains via dynamic covalent bonds (e.g., Schiff base bonds, and boronate ester bonds) and supramolecular interactions (e.g., hydrogen bonding, π-π stacking, electrostatic interactions). Compared to traditional hydrogels, glycopeptide hydrogels demonstrate superior dynamic responsiveness, enhanced bioactivity, and excellent mechanical properties. This research topic focuses on three key dimensions of glycopeptide hydrogels-molecular design, mechanical regulation, and advanced processing-summarizing representative research progress and discussing their potential role and value in tissue engineering (Figure 1).The core of glycopeptide hydrogel molecular composition design lies in mimicking the chemical constituents and biological functions of the natural ECM (Figure 2), achieving structural biomimicry or metabolic microenvironment regulation through precise assembly of polysaccharides and peptides to promote tissue regeneration. As exemplified by the design strategy of constructing dynamic crosslinked networks through the introduction of reversible dynamic covalent bonds, glycopeptide hydrogels are endowed with precise control over their degradation behavior. Furthermore, such biomimetic mechanisms endow glycopeptide hydrogels with cell signaling characteristics. On one hand, peptide sequences (such as RGD) bind to integrins on the cell surface, activating mechanotransduction pathways such as focal adhesion kinase, thus providing a favorable environment for cell adhesion, proliferation, and signal transduction. On the other hand, sugar moieties (such as mannose) specifically bind to receptors on immune cell surfaces, triggering specific immune modulation. This material can also possess dynamic responsiveness, achieving matrix remodeling on demand through enzymatic degradation sites or utilizing dynamic bonds for the time-controlled release of growth factors. Consequently, this integrated design coordinates structural, mechanical, and biochemical signals to synergistically regulate cell.Traditional single-component hydrogels struggle to fully provide the multidimensional biological signals required by the ECM. In contrast, glycopeptide hydrogels closely mimic the molecular composition of the native ECM, which forms the basis for their superior biological functionality. It has been elucidated that integrating fungal extracts with natural antiinflammatory activity (primarily composed of polysaccharides) into a biomimetic hydrogel system can synergistically leverage the material's physical barrier function and the pharmacological effects of the active components, enabling precise regulation of the inflammatory microenvironment in wounds (Arbab et al., 2024). Guo et al. (Guo et al., 2025) developed an injectable, self-healing glycopeptide hydrogels (OGA-CMCS) formed through a dynamic Schiff base reaction between oxidized glycyrrhizic acid (OGA) and carboxymethyl chitosan (CMCS). This hydrogel mimics the structure and dynamic microenvironment of native ECM glycoproteins, achieving anti-inflammatory and antibacterial effects in acute wounds, as well as inducing macrophage M2 polarization to promote tissue regeneration. This design strategy for glycopeptide hydrogels based on natural bioactive molecules achieves precise biomimicry of ECM structure and function at the molecular composition level, offering an ideal cellular support platform for tissue regeneration. Furthermore, the network structure of this hydrogel is precisely based on reversible Schiff base dynamic bonds, whose hydrolysis rate can be flexibly regulated through crosslinking density and the chemical microenvironment. It has been confirmed that by adjusting the degree of oxidation, a tunable degradation window ranging from several days to two weeks can be achieved, enabling the matching of degradation rate with the tissue regeneration process. This design strategy based on dynamic chemistry represents a key advantage of glycopeptide hydrogels over traditional statically crosslinked hydrogels, providing a molecular foundation for their programmed degradation and on-demand therapeutic application.An ideal tissue engineering scaffold requires not only chemical biomimicry but also precise matching of the mechanical properties of native tissues to achieve physical regulation of cellular behavior. For instance, a study developed a hyaluronic acid-based double-network hydrogel that allows independent tuning of stiffness and viscoelasticity, thereby enabling investigation of how tissue mechanics and immune cells (macrophages) involved in the fibrotic process synergistically (Astrab et al., 2025). Zhang et al. (Zhang et al., 2025) systematically elaborated on the design principles and functional optimization strategies for glycopeptide hydrogels, with particular emphasis on the pivotal role of dynamic crosslinking strategies in optimizing their mechanical performance. By modulating the dynamic covalent bonds and supramolecular interactions between sugars and peptides, the viscoelasticity, self-healing capability, and shear-thinning properties of the hydrogels were significantly enhanced. This dynamic mechanical...