During bone defect repair, the phenotypes, differentiation, and paracrine functions of both macrophages (Mφ) and mesenchymal stem cells (MSCs) are critically regulated by matrix stiffness. These two cell types interact via paracrine signaling, forming a bidirectional "immune-osteogenic" regulatory axis that jointly drives bone regeneration. Based on this, the present study employed a dynamically stiffening hydrogel system based on calcium ion-crosslinked gelatin/sodium alginate (Gel/SA), combined with a conditioned medium (CM)-based coculture model, to investigate the interaction between Mφ and MSCs under conditions of dynamic matrix stiffness evolution. Experimental results demonstrated that dynamic stiffness, together with inflammatory factors secreted by stiffness-modulated Mφ, synergistically enhanced the osteogenic differentiation of MSCs, leading to significantly higher differentiation levels in the dynamic stiffness group compared to other groups. Meanwhile, dynamic stiffness, along with prostaglandin E2 (PGE2) secreted by stiffness-modulated MSCs, collectively influenced Mφ, resulting in an inflammatory factor expression profile intermediate between those in the high- and low-stiffness groups. The data demonstrated that dynamic rigidity steers Mφ polarization and MSCs immunomodulation, and that dynamic stiffness-mediated Mφ-MSCs crosstalk tailors the injury microenvironment to accelerate early osteogenic commitment. These findings reveal the mechanism by which dynamic matrix mechanics guide bone regeneration through modulation of the early inflammatory microenvironment.

Immunotherapy has emerged as a new clinical paradigm for cancer management, leveraging immunomodulation to enhance systemic antitumor responses. Despite its significant potency and distinct advantages, challenges such as limited patient response rates and immune-related toxicities persist. Although nanomaterial-based delivery systems have been explored to improve local drug retention within tumor tissues, the efficacy of systemic nanomaterial strategies is constrained by low bioavailability and poor tumor penetration. As innovative localized delivery systems, injectable hydrogels hold significant promise in overcoming these challenges. Capitalizing on their inherent biocompatibility, tailorable physicochemical characteristics, and biomimetic interactions with the extracellular matrix, these hydrogel systems can be engineered to achieve precise therapeutic delivery with enhanced stability and bioavailability. Additionally, they enable the combination of immunotherapy with complementary treatment modalities, such as chemotherapy, radiotherapy, phototherapy, sonodynamic therapy, and oncolytic virotherapy. This review begins by outlining the key steps of the cancer-immunity cycle, along with existing immunotherapeutic approaches and their inherent limitations. Then, we outline the design principles of hydrogel-based therapeutic delivery systems for cancer immunotherapy. Additionally, it summarizes recent advances in developing functional hydrogels for the localized delivery of small molecules, macromolecules, and immune cells to elicit robust antitumor immune responses. Moreover, we explore the potential benefits of hydrogel-based combination immunotherapy in enhancing therapeutic outcomes. Finally, we discuss the critical challenges and future perspectives for the clinical translation of hydrogel-based cancer immunotherapies.

The process of wound healing is intricate and, once disrupted, results in scar formation. Scar formation has negative physiological and psychological impacts on patients in addition to impeding the restoration of skin integrity and function. Increasing evidence indicates that factors such as angiogenesis, ECM deposition, and inflammation are all associated with scar formation. Given their excellent immunomodulatory and regenerative properties, mesenchymal stem cell-derived exosomes (MSCs-Exos) are increasingly favored in inhibiting scar formation during wound healing. This review begins with a summary of the key mechanisms of wound healing and scar formation, followed by the application of MSCs-Exos in attenuating the pathological process of scar formation, as well as its potential mechanisms of action. In addition, the current status and development prospects of engineered exosomes and hydrogel-combined exosomes in scar inhibition are further discussed. Finally, we evaluate the current challenges of using exosomes for scarless wound healing, including manufacturing standardization, dosing, delivery systems, and the lack of large-scale clinical data, which hold the potential to bridge the gap between the laboratory and the clinical.

Continuous health monitoring is essential for the management of cardiovascular and musculoskeletal disorders. Fiber-based electronics are widely recognized as ideal platforms for such applications, owing to their superior comfort and seamless integrability with textiles. However, advances in this field have been hindered by two major challenges: limitations in manufacturing processes and functional isolation among components. Here, a multifunctional ionic wrinkled fiber was developed by creating micro-wrinkles through a pre-stretch-coat-release strategy. This process was applied to a spandex fiber substrate coated with a composite electrode and an ionic thermoplastic polyurethane sensing layer. The micro-wrinkles act as mechanical signal amplifiers that work in synergy with an ionic capacitive sensing mechanism, endowing assembled devices with outstanding sensing performance-including a high pressure sensitivity of 2.8 kPa(-1) in an orthogonal cross-point architecture and a gauge factor of 1.79 as a single-fiber strain sensor. Additionally, the fiber exhibits efficient Joule heating, ultrahigh stretchability (>450%), and excellent cyclic stability. To demonstrate its practical utility, two system-level platforms were constructed: a proactive closed-loop system for preventing carpal tunnel syndrome and a smart glove for enhanced human-machine interaction. This microstructuring strategy effectively enhances the sensitivity of fiber-based sensors, paving the way for next-generation health management systems that transition from passive monitoring to active, closed-loop therapeutic interventions.

Liver fibrosis is a hallmark pathological feature of chronic liver diseases and poses a major threat to the health of millions of people worldwide. Without timely diagnosis and effective intervention, liver fibrosis can progress to cirrhosis, liver failure, and even hepatocellular carcinoma (HCC). The limited availability of donor organs for orthotopic liver transplantation has driven the continuous search for alternative therapeutic strategies. However, conventional approaches, including pharmacotherapy, RNA-based therapies, and cell therapy, are often limited by insufficient therapeutic efficacy, poor targeting, and significant adverse effects, underscoring the urgent need for more effective treatment strategies. In recent years, biomaterials have emerged as promising platforms for liver fibrosis therapy owing to their excellent biocompatibility and tunable physicochemical properties. This review summarizes the recent advances in biomaterial-based therapeutic strategies for liver fibrosis, with a particular focus on nanomaterials, hydrogels, and microsphere-based delivery systems. The advantages and limitations of these biomaterial platforms are systematically discussed. Furthermore, we highlight the dual role of biomaterials not only as delivery vehicles for antifibrotic drugs, nucleic acids, and therapeutic cells but also as active platforms that modulate the fibrotic microenvironment and promote liver regeneration. Finally, the current status and future perspectives of biomaterial-based approaches in liver tissue engineering are discussed.

Conventional static biomaterials possess relatively stable physicochemical properties after fabrication or implantation, which limits their ability to adapt to dynamically changing physiological microenvironments. In contrast, dynamic biomaterials can undergo controllable or programmable changes to regulate their physicochemical properties in response to external or endogenous stimuli, thereby providing improved spatiotemporal adaptability for biomedical applications. In this review, dynamic biomaterials are systematically discussed from a physical-cue-centered perspective, focusing on stimulus-responsive changes in stiffness, surface morphology, and shape programmability rather than classification solely by stimulus type or material composition. The responsive mechanisms, preparation strategies, and representative stimuli, including light, temperature, pH, ions, and magnetic fields, are summarized and critically analyzed. Recent biomedical applications in tissue engineering, drug delivery, minimally invasive therapy, and intelligent biomedical devices are further highlighted. Finally, current challenges involving long-term biosafety, mechanical durability, manufacturability, and clinical translation are discussed, together with future perspectives for multifunctional, multi-stimuli-responsive, and spatiotemporally programmable dynamic biomaterials.

Liquid metal (LM) nanoparticles have been widely used in photothermal therapy (PTT), but they are susceptible to oxidative inactivation and have poor targeting ability. Platelets (PLT) have many abundant membrane proteins on their surface that can be used to modify LM nanoparticles. Here, a gallium (Ga)-based LM-based nanoparticle delivery system was developed. The conducting polymer polypyrrole (PPy) was first grown in situ on the surface of LM nanoparticles by polymerization (named as LM@PPy). The oxidation resistance and photothermal stability of LM were improved. Subsequently, PLT membrane (PM) was extracted and coated on the surface of LM@PPy to prepare LM@PPy/PM. The antitumor effect of LM@PPy/PM was investigated through in vitro and in vivo experiments. It was demonstrated that the LM@PPy had better photothermal stability and their photothermal conversion efficiency reached 55 +/- 2 %, which was higher than that of unmodified LM nanoparticles (31 +/- 2 %). Most of the membrane proteins from PLT were retained on the prepared LM@PPy/PM. The PM coating effectively enhanced the tumor-targeting ability of the nanoparticles, leading to better tumor accumulation and antitumor effects in in vitro and in vivo. The findings showed that this nanoparticle delivery system provided a new technological solution to improve the antitumor ability of LM nanoparticles.

Peripheral nerves and blood vessels regulate the development process of bone tissue by delivering neural and vascular-related cytokines. However, challenge of preventing the loss of neural and vascular growth factors and ensuring their long-term availability for bone defects was often been overlooked. The current study designed a hybrid cell membrane with specific surface receptors for calcitonin receptor (CTR) and vascular endothelial growth factor receptor (VEGFR) through overexpressed the CTR receptor gene (Calcr) and the VEGFR 1 gene (Flt-1). The bone repair matrix functionalized by the hybrid cell membrane (GCMs) had collecting property for neurogenic growth factor (NGF) and vascular endothelial growth factor (VEGF). Furthermore, GCMs enhanced neural and vascular differentiation in mesenchymal stem cells (MSCs) and stimulated osteogenic differentiation of MSCs through neural and vascular-related paracrine signals. GCMs also facilitated the angiogenesis and neurogenesis around bone defects, further promoted the repair of rat skull defects. This study suggests a promising approach for using cell membranes to harvest growth factors for innervation and vascularization in bone reconstruction.

In the repair of large bone defects, loss of the periosteum can result in diminished osteoinductive activity, nonunion, and incomplete regeneration of the bone structure, ultimately compromising the efficiency of bone regeneration. Therefore, the research and development of tissue-engineered periosteum which can replace the periosteum function has become the focus of current research. The functionalized electrospinning periosteum is expected to mimic the natural periosteum and enhance bone repair processes more effectively. This review explores the construction strategies for functionalized electrospun periosteum from the following perspectives: ⅰ) bioactive factor modification (bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF) etc.), ⅱ) inorganic compound modification, ⅲ) drug modification, ⅳ) artificial periosteum in response to physical stimuli. Furthermore, the construction of artificial periosteum through electrospinning, in conjunction with other strategies, is also analyzed. Finally, the current challenges and prospects for the development of electrospinning periosteum are also discussed.

Thrombin is central to the process of the coagulation cascade reaction, and its activity directly affects fibrin formation and final hemostasis. Nanomaterial-based hemostatic agents have exhibited excellent performance in hemorrhage management. The unique exposed crystal facets of nanomaterials play a crucial role in catalytic reactions but are often overlooked. Here, a series of nanoscale zeolitic imidazolate frameworks (denoted as ZIF-8/C with exposed (100) facet, ZIF-8/TRD with mixed exposed (100) and (110) facets, and ZIF-8/RD with exposed (110) facet) were successfully synthesized with crystal facets progressively evolving from (100) to (110), which serve as catalytic platforms to accelerate the process of the coagulation cascade reaction by modulating the activity of thrombin immobilized on their surfaces. ZIF-8/TRD exhibited a striking catalytic capacity with at least 13-fold higher levels of thrombin expression compared with natural platelet-based physiological processes. Molecular dynamics (MD) simulations revealed that the special mixed-facet environment increased substrate accessibility and exhibited a more stable active site conformation. This work focuses on the regulation of enzymatic reactions carried out on the protein corona of the host material by crystal facets, paving the way for the design of hemostatic agents with enhanced thrombin activity.

In most studies, the penetration of nanoparticles into tumors was mainly dependent on the enhanced permeability and retention (ERP) effect. However, the penetration of nanoparticles would be limited by tumor-dense structure, immune system, and other factors. To solve these problems, macrophages with active tropism to tumor tissues, loaded nanoparticles with photothermal therapy, and chemotherapy were designed. In detail, liquid metal (gallium indium alloy) nanoparticles were modified with mesoporous silica and then embedded with the chemotherapeutic drug sorafenib (LM@Si/SO) for photothermal therapy and chemotherapy. After that, the LM@Si/SO nanoparticles were carried by the mouse macrophage RAW264.7 cell line (LM@Si/SO@R) to increase the accumulation of the nanoparticles in the tumor site and improve the tumor immune microenvironment. With the enhanced tumor accumulation, LM@Si/SO@R exhibited excellent antitumor ability in vitro and in vivo. Thus, these strategies via the cell carrier to enhance tumor therapeutic efficiency had the potential for the improvement of tumor therapy.

The extracellular matrix (ECM) maintains tissue morphology and regulates cellular behavior through its network of biochemical components and biophysical signals. Matrix stiffness, as a key physical parameter in cell-matrix interactions, has attracted widespread attention and has been recognized as a crucial regulator of cellular behavior. Tissue engineering mimics the biomechanical environment of the ECM to promote the repair of damaged tissues. In this context, gelatin methacryloyl (GelMA), a photocrosslinkable hydrogel, has emerged as a pivotal platform in tissue engineering due to its excellent biocompatibility, biodegradability, and tunable mechanical properties. This review systematically summarizes various strategies for modulating GelMA stiffness, including adjusting the crosslinking density, incorporating nanomaterials, optimizing photopolymerization parameters, and integrating bioactive components. Furthermore, the mechanisms by which GelMA stiffness influences cellular behavior through mechanotransduction are discussed, with a focus on integrin signaling pathways, cytoskeletal remodeling, and transcription factors such as YAP/TAZ. The review also highlights applications of tuned-stiffness GelMA scaffolds in bone, skin, cardiac, and neural tissue engineering, underscoring their potential for functional repair via biomimetic mechanics. Finally, the review emphasizes the need for future research to further explore synergistic interactions between stiffness, dynamic degradation, and biological signaling mechanisms, to advance the clinical translation of GelMA in regenerative medicine.

The combination of nerve guide conduits (NGCs) and electrical stimulation (ES) is an effective treatment for peripheral nerve injury (PNI). Flexible conductive materials with mechanical properties similar to those of biological tissues have been shown to have better long-term biointegration and functionality than rigid conductive materials. In this study, liquid metal (LM)-based conductive polycaprolactone/gelatin/polypyrrole/LM (PCL/Gel/PPy/LM, PGPL) NGC was combined with exogenous ES to repair PNI. PGPL membranes had good hydrophilicity, degradability, and mechanical properties, and its conductivity reached 0.66 ± 0.02 S/m. In vitro studies showed that the combination of PGPL membranes and ES (2 Hz, 100 mV/cm, 30 min/d) could significantly increase the expression of neuromarkers and had a better pro-neural differentiation effect. In vivo studies demonstrated that PGPL NGCs in combination with ES (2 Hz, 200 mV/mm, 30 min/d) could effectively promote morphological reconstruction and functional recovery of the sciatic nerve in rats. At 3 months post-surgery, PGPL NGCs combined with ES restored the nerve conduction velocity to 73.85% ± 5.45% of the normal value. The LM-based NGCs prepared in this study could effectively repair long sciatic nerve defects, which may further expand the application of LM in the field of nerve tissue engineering.

Owning to seriously impaired capacity of bone regeneration, the repair of osteoporotic bone defect remains a major clinical challenge in orthopedics. For titanium mesh scaffolds of skull repair, to construct bio-coatings targeting the pathological environment of osteoporosis is significant. Here, tannic acid (TA)/casein phosphopeptide (CPP) based layer-by-layer (LBL) self-assembled coating that loaded with anti-osteoporotic alendronate sodium (AS) and bioactive Mg2+ were prepared. The TA/CPP based LBL coatings showed good antioxidative function to effectively clear ABTS+• free radicals (scavenging rate of 64.29 ± 20.21 %) and inhibited the production of reactive oxygen species (ROS) in bone marrow mesenchymal stem cells (BMSCs) under oxidative stress conditions. All the LBL coatings exhibited good blood compatibility, and promoted early adhesion of BMSCs without affecting cell proliferation. In particular, the (TA/CPP-AS NPs)4 + Mg2+coatings had both good alkaline phosphatase (ALP) activity and in vitro osteogenic mineralization, and could effectively promote the migration of human umbilical vein endothelial cells (HUVECs). In 8-weeks in vivo implantation experiments of osteoporotic skull defects, AS and Mg2+ loaded LBL coating showed significant formation of new bone tissue. The study on the integrated system of antioxidative coating with bisphosphonates and active metal ions will serve as a promising strategy for osteoporotic bone defect repair.

During tendon injury repair, deficiency of basic fibroblast growth factor (bFGF) is a critical factor leading to unsatisfactory repair results. This study aims to prepare bFGF-loaded zeolite imidazole framework-8 (ZIF-8) nanocrystals using a one-pot synthesis method. Subsequently, a bilayer nanofibrous membrane incorporating these drug-loaded nanocrystals was fabricated through electrospinning technology. The potential of this composite nanofibrous membrane to facilitate the continuous release of bFGF at the site of tendon injury was evaluated, with the aim of enhancing the quality of tendon repair. The efficacy of the nanofibrous membrane in promoting tendon differentiation, preventing tendon adhesion, and facilitating tendon repair was assessed through both in vitro and in vivo experiments. At the site of tendon injury, the degradation of ZIF-8 in an acidic microenvironment resulted in the release of bFGF and Zn2+, which contributed to the enhancement of tendon repair. ZIF-8 nanocrystals achieved an encapsulation efficiency of 50.13% ± 1.42%. Following a continuous release period exceeding 40 days, the cumulative in vitro release rate was determined to be 35.02% ± 4.27%. The incorporation of ZIF-8 nanocrystals into a nanofibrous membrane demonstrated the ability to effectively preserve the bioactivity of bFGF while enabling sustained release at the site of tendon injury, thereby facilitating tendon repair. The findings offer novel insights into the treatment of tendon injuries and provide significant theoretical guidance for the tendon repair process.

The overproduction of reactive oxygen and nitrogen species (RONS) is tightly related to various diseases. Previous radical scavenging agents usually focus on biomaterials or noble metals, suffering from problems of stability and cost. Few nonmetallic agents have been reported for the RONS scavenging with enzyme-like activity. Herein, a series of three isoreticular metal-organic frameworks (MOFs) are specifically designed based on the UiO-68-type structure, in which a molecular platform derived from a rigid N-heterocycle has been attached to the backbone of MOFs by mimicking the structure of a Se-based antioxidative enzyme termed as selenoneine. Precise manipulation of three chalcogen atoms (O, S, and Se) has been successfully achieved in three similar N-heterocycles, that is, phenoxazine (PXZ), phenothiazine (PTZ), and phenoselenazine (PSZ). Two MOFs in this series exhibited excellent elimination efficiencies in radical solutions of 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO) and 2,2 '-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), that is, 80% clearance of PTIO radical in 2 h by UiO-68-PTZ and nearly 100% clearance of ABTS+ in 5 min by UiO-68-PSZ. The scavenging mechanisms of PTIO and ABTS+ have been further revealed and demonstrated by experiments and theoretical calculations, in which the S site and Se site can selectively scavenge the radicals through binding interaction with the PTIO radical or electron transfer with ABTS+.

Conductive hydrogel‐based triboelectric nanogenerator (TENG) is widely used in multiple fields. The incompatibility of conductive filler and hydrogel electrode may result in stress concentration or damage within hydrogel, thereby impacting the long‐term stability of TENG. Herein, a poly(vinyl alcohol) (PVA) hydrogel/liquid metal (LM) TENG is presented with simple fabrication, high output performance, and versatile applications. Flexible LM is incorporated into both the PVA hydrogel‐based electrode and Ecoflex friction layer to fabricate the PLL‐TENG (TENG of Ecoflex/LM friction material‐coated PVA/LM hydrogel electrodes). The LM doped into the Ecoflex friction layer improves the dielectric constant of the friction layer, resulting in the electrical performance of the constructed PLL‐TENG being 1.5 times that of the TENG with a pure Ecoflex friction layer (PL‐TENG). In single‐electrode mode, the open‐circuit voltage is 275 V, the short‐circuit current is 4.8 μA, and the transferred charge is 118 nC. The PLL‐TENG could easily light up to 293 light‐emitting diodes. In addition to energy harvesting, the PLL‐TENG has potential applications in wearable motion monitoring, high‐precision writing stroke recognition, and various other fields. This study presents substantial potential for the development of advanced materials and devices in the domains of flexible wearable sensors, electronic skin, and intelligent robotics.

Temperature-dependent photothermal therapy (PTT) has emerged as a promising non-invasive strategy for cancer treatment. However, its efficacy is constrained by a critical trade-off: while high-temperature PTT is potent, it often triggers detrimental inflammatory responses that can cause tissue damage and promote tumor recurrence; conversely, low-temperature PTT minimizes collateral damage but is frequently undermined by heat shock proteins (HSPs)-induced thermoresistance. Reductive gas therapy (GT), utilizing molecules such as carbon monoxide (CO), hydrogen sulfide (H2S), and hydrogen (H2), offers a promising avenue to overcome these limitations. This review posits that the synergy between reductive gases and PTT is fundamentally rooted in a dual mechanism of mitochondrial regulation. The primary mechanism involves gas-induced mitochondrial dysfunction, which disrupts oxidative phosphorylation and depletes cellular adenosine triphosphate (ATP). Given the high ATP-dependency of HSPs chaperone function, this energy crisis directly cripples the thermoresistance machinery, thereby sensitizing cancer cells to low-temperature PTT. The secondary, complementary mechanism leverages the potent anti-inflammatory and antioxidant properties of these gases. By scavenging reactive oxygen and nitrogen species and modulating pro-inflammatory pathways such as nuclear factor kappa B (NF-κB), they effectively mitigate the harmful inflammation and oxidative stress associated with high-temperature PTT, reducing side effects and improving treatment safety. Furthermore, the integration of PTT/GT with other treatment modalities within a multimodal strategy can yield enhanced therapeutic outcomes. This review provides a comprehensive summary of recent advancements in reductive gas-enhanced cancer PTT. It begins with an overview of stimuli-responsive gas-generating systems, then discusses their application in both anti-inflammation-boosted high-temperature PTT and HSPs downregulation-promoted low-temperature PTT, respectively. Finally, the review addresses potential challenges and future directions, serving as a valuable resource for the continued development of photothermal/gas-based nanomedicines.

Bone formation is a dynamic process, while the stiffness of extracellular matrix increases dynamically during bone maturation. Matrix stiffness can significantly regulate the stem cell differentiation and bone repair. It is particularly important to develop dynamic stiffness scaffolds to simulate dynamic mechanical microenvironment for bone repair. This study proposed a novel method to achieve dynamic improvement of scaffold stiffness by mineralization, which is a natural process of bone matrix dynamic stiffening. The decalcified bone matrix (DBM)/collagen (Col)/silicon-substituted hydroxyapatite (SiHA) scaffold was constructed by coating the Col/SiHA on the surface of DBM. When the scaffolds contacted with body fluid, the stiffness of scaffolds were enhanced by mineralization, increasing from 9.10 ± 4.42 kPa to 19.77 ± 9.66 kPa in the DBM/Col scaffold and from 40.54 ± 6.25 kPa to 69.40 ± 8.76 kPa in the DBM/Col/SiHA scaffold. The experimental results proved that the DBM/Col/SiHA scaffold with dynamic stiffness had good biocompatibility and could promote the osteogenic differentiation of mesenchymal stem cell. The DBM/Col/SiHA scaffold, when implanted in a rat calvarial defect model, further enhanced bone regeneration and integration, as evidenced by a bone mineral density reaching 285.592 ± 19.611 mg HA ccm −1 at 12 weeks. This research may provide new insights into the application of mineralization-dependent stiffening scaffolds in bone tissue engineering.