Metal ion-promoted chemodynamic therapy(CDT) combined with photodynamic therapy(PDT) offers broad application prospects for enhancing anti-tumor effects. In this study, glycyrrhizic acid(GA), copper ions(Cu~(2+)), and norcantharidin(NCTD) were co-assembled to successfully prepare a natural small-molecule, carrier-free hydrogel(NCTD Gel) with excellent material properties. Under 808 nm laser irradiation, NCTD Gel responded to the tumor microenvironment(TME) and acted as an efficient Fenton reagent and photosensitizer, catalyzing the conversion of endogenous hydrogen peroxide(H_2O_2) within the tumor into oxygen(O_2), and hydroxyl radicals(·OH, type Ⅰ reactive oxygen species) and singlet oxygen(~1O_2, type Ⅱ reactive oxygen species), while depleting glutathione(GSH) to stabilize reactive oxygen species and alleviate tumor hypoxia. In vitro and in vivo experiments demonstrated that NCTD Gel exhibited significant CDT/PDT synergistic therapeutic effects. Further safety evaluation and metabolic testing confirmed its good biocompatibility and safety. This novel hydrogel is not only simple to prepare, safe, and cost-effective but also holds great potential for clinical transformation, providing insights and references for the research and development of metal ion-mediated hydrogel-based anti-tumor therapies.
Hydrogels/chemistry* ; Animals ; Photochemotherapy ; Humans ; Mice ; Antineoplastic Agents/administration & dosage* ; Photosensitizing Agents/chemistry* ; Neoplasms/metabolism* ; Female ; Copper/chemistry* ; Reactive Oxygen Species/metabolism* ; Tumor Microenvironment/drug effects* ; Cell Line, Tumor ; Male

OBJECTIVE: To summarize the research progress of bioactive scaffolds in the repair and regeneration of osteoporotic bone defects. METHODS: Recent literature on bioactive scaffolds for the repair of osteoporotic bone defects was reviewed to summarize various types of bioactive scaffolds and their associated repair methods. RESULTS: The application of bioactive scaffolds provides a new idea for the repair and regeneration of osteoporotic bone defects. For example, calcium phosphate ceramics scaffolds, hydrogel scaffolds, three-dimensional (3D)-printed biological scaffolds, metal scaffolds, as well as polymer material scaffolds and bone organoids, have all demonstrated good bone repair-promoting effects. However, in the pathological bone microenvironment of osteoporosis, the function of single-material scaffolds to promote bone regeneration is insufficient. Therefore, the design of bioactive scaffolds must consider multiple factors, including material biocompatibility, mechanical properties, bioactivity, bone conductivity, and osteogenic induction. Furthermore, physical and chemical surface modifications, along with advanced biotechnological approaches, can help to improve the osteogenic microenvironment and promote the differentiation of bone cells. CONCLUSION With advancements in technology, the synergistic application of 3D bioprinting, bone organoids technologies, and advanced biotechnologies holds promise for providing more efficient bioactive scaffolds for the repair and regeneration of osteoporotic bone defects.
Humans ; Tissue Scaffolds/chemistry* ; Bone Regeneration ; Osteoporosis/therapy* ; Tissue Engineering/methods* ; Biocompatible Materials/chemistry* ; Printing, Three-Dimensional ; Calcium Phosphates/chemistry* ; Osteogenesis ; Ceramics ; Cell Differentiation ; Hydrogels ; Bioprinting ; Bone and Bones

OBJECTIVE: To review clinical application and research progress of different types of intelligent responsive hydrogels in repairing articular cartilage injury. METHODS: The animal experiments and clinical studies of different types of intelligent responsive hydrogels for repairing articular cartilage injury were summarized by reviewing relevant literature at home and abroad. RESULTS: The intrinsic regenerative capacity of articular cartilage following injury is limited. Intelligent responsive hydrogels, including those that are temperature-sensitive, light-sensitive, enzyme-responsive, pH-sensitive, and other stimuli-responsive hydrogels, can undergo phase transitions in response to specific stimuli, thereby achieving optimal functionality. These hydrogels can fill the injured cartilage area, promote the proliferation and differentiation of chondrocytes, and expedite the repair of the damaged site. With advancements in cartilage tissue engineering materials research, intelligent responsive hydrogels offer a novel approach and promising potential for the treatment of cartilage injuries. CONCLUSION Intelligent responsive hydrogel is a kind of flexible, controllable, efficient, and stable polymer, which has similar structure and functional properties to articular cartilage, and has become one of the important biomaterials for cartilage repair. However, there is still a lack of unified treatment standards and simple and efficient preparation technology.
Hydrogels/therapeutic use* ; Cartilage, Articular/injuries* ; Tissue Engineering/methods* ; Humans ; Animals ; Chondrocytes/cytology* ; Biocompatible Materials/chemistry* ; Tissue Scaffolds/chemistry*

OBJECTIVE: To summarize recent research progress in hydrogel-based growth factors for treatment of intervertebral disc degeneration (IDD). METHODS: The relevant literature on hydrogel-based growth factors for IDD treatment at home and abroad was extensively reviewed, and their advantages and therapeutic effects in repairing IDD were analyzed and summarized. RESULTS: Hydrogels exhibit high hydration, biocompatibility, and biodegradability, enabling targeted delivery and sustained release of growth factors such as growth differentiation factors and transforming growth factors. This facilitates enhanced efficacy in promoting cell proliferation, extracellular matrix synthesis, and reducing inflammatory responses. Consequently, hydrogels demonstrate broad application prospects in the repair of IDD. CONCLUSION Research on hydrogel-based growth factors for treating IDD demonstrates advantages such as avoiding disc damage caused by repeated injections and controlling growth factor release concentrations. However, drawbacks include the limited variety of loaded growth factors and the need to verify the long-term stability and biocompatibility of hydrogels. Therefore, further research is required on aspects such as the types of loaded growth factors and the long-term stability and biocompatibility of hydrogels to establish an experimental foundation for their clinical application.
Intervertebral Disc Degeneration/therapy* ; Hydrogels/chemistry* ; Humans ; Intercellular Signaling Peptides and Proteins/administration & dosage* ; Biocompatible Materials/chemistry* ; Animals ; Tissue Engineering/methods* ; Cell Proliferation/drug effects* ; Drug Delivery Systems

Adoptive cell transfer (ACT) shows significant efficacy against hema-tological malignancies but is limited in solid tumors due to poor homing, immunosuppre-ssion, and potential toxicity. Biomaterials spanning from nano- to macroscales-including nanoparticles, microspheres/micropatches, and hydrogels-offer unique advantages for ex vivo cell engineering, in vivo delivery, and modulation of the tumor microenvironment. Specifically, nanoparticles enable gene delivery, artificial antigen-presenting cell engi-neering, and immune microenvironment remodeling. Microspheres/micropatches improve immune cell expansion, targeted activation, and localized retention. Hydrogels enhance ACT via in situ genetic engineering, 3D culture support, and cytokine co-delivery. This review summarizes advances in biomaterial-enhanced ACT, highlighting their potential to improve delivery efficiency, amplify antitumor responses, and reduce toxicity. These insights may accelerate the clinical translation of ACT for solid tumors.
Humans ; Neoplasms/therapy* ; Biocompatible Materials/chemistry* ; Immunotherapy, Adoptive/methods* ; Nanoparticles ; Hydrogels ; Adoptive Transfer/methods* ; Animals

Myocardial infarction is a cardiovascular disease with high morbidity and mortality rates. Hydrogel biomaterials mimicking the extracellular matrix have recently been shown to demonstrate excellent biocompatibility, low immunogenicity, favorable biodegradability, and multifunctionality, showcasing significant potential for treatment of myocardial infarction. Hydrogels can provide mechanical support to the damaged myo-cardium, alleviating pathological remodeling. Moreover, their porous structure makes them ideal carriers for localized and sustained drug delivery. Hydrogels derived from various matrices-including polysaccharides, polypeptides, proteins, decellularized extracellular matrix, and synthetic polymers-exhibit distinct properties in terms of biocompatibility, mechanical performance, and drug delivery capacity. These hydrogels support tissue regeneration and enable targeted release of diverse therapeutics, meeting the various therapeutic demands for myocardial repair. In the infarcted myocardial microenvironment, endogenous signals such as low pH, specific enzyme expression, and elevated levels of reactive oxygen species can trigger responsive drug release from hydrogels, while external physical stimuli-such as ultrasound, light, and magnetic fields-can also be employed to precisely control the release process, thereby enhancing therapeutic efficacy and reducing systemic side effects. This review summarizes recent advances in hydrogel-based drug delivery systems for treatment of myocardial infarction, focusing particularly on the characteristics and advantages of different hydrogel materials for myocardial repair. Furthermore, the responsive drug release behavior of hydrogels is analyzed in the context of the cardiac injury microenvironment, providing a reference for future research.
Hydrogels/chemistry* ; Myocardial Infarction/drug therapy* ; Humans ; Drug Delivery Systems/methods* ; Biocompatible Materials ; Drug Carriers

OBJECTIVES: To fabricate an injectable composite microsphere hydrogel reinforced with silk fibroin/hyaluronic acid microspheres, achieving synergistic enhance-ment of mechanical robustness and biofunctionality. METHODS: Methacrylated hyaluronic acid (HAMA) and thiolated silk fibroin (TSF) were synthesized. Monodisperse microspheres generated via microfluidics were UV-cured (420 nm) through thiol-ene click reaction. These microspheres were embedded in a TSF/HAMA matrix to form photo-cured composites. The grafting rate of TSF and HAMA was characterized by H1-NMR; particle size distribution of microsphere hydrogels in soybean oil was observed by optical microscopy; gel point of composite microsphere hydrogels was determined by advanced extensional rheometer; microscopic morphology of microsphere hydrogels was observed by scanning electron microscopy; elemental distribution of microsphere hydrogels was detected by X-ray energy dispersive spectroscopy; tunability of composite microsphere hydrogels was observed by inverted confocal microscopy; mechanical properties of composite microsphere hydrogels were tested by compression testing; swelling ratio, degradation rate and water retention rate of composite microsphere hydrogels were measured by gravimetric method. Cytotoxicity of the composite microsphere hydrogels was determined by Calcein-AM/propidium iodide dual staining and CCK-8 assay; cell migration capability was observed by scratch assay. RESULTS: The grafting rates of HAMA and TSF was 48.03% and 17.99%, respectively. Microsphere hydrogels with particle sizes of (43.3±1.2), (78.1±3.0), and (130.8±1.9) μm were prepared. The gel time of the composite microsphere hydrogels was 48-115s. The laser confocal imaging confirmed dynamic regulation characteristics of the composite microsphere hydrogels. The compressive strength of the composite microsphere hydrogels reached 22.7 kPa and maintained structural integrity at 40% strain after 20 compression cycles. The composite microsphere hydrogels exhibited differential deswelling behaviors in simulated physiological environments, and reducing microsphere particle size could significantly enhance its stability under moist conditions. The degradation rate of the composite microsphere hydrogels was (49.1±0.9)% after 200 h, and water retention rate was maintained at 40%-60% after 96 h. Biocompatibility assays confirmed >95% cell viability and unimpaired cell migration abilities. CONCLUSIONS The TSF/HAMA composite microsphere hydrogel developed in this study has characteristics of rapid fabrication, adjustable mechanical properties, enhanced environmental stability and excellent biocom-patibility, thus providing a new material solution for tissue repair and regenerative medicine.
Fibroins/chemistry* ; Hydrogels/chemistry* ; Microspheres ; Hyaluronic Acid/chemistry* ; Humans

Xerostomia (dry mouth) is frequently experienced by patients treated with radiotherapy for head and neck cancers or with Sjögren's syndrome, with no permanent cure existing for this debilitating condition. To this end, in vitro platforms are needed to test therapies directed at salivary (fluid-secreting) cells. However, since these are highly differentiated secretory cells, the maintenance of their differentiated state while expanding in numbers is challenging. In this study, the efficiency of three reversible thermo-ionically crosslinked gels: (1) alginate-gelatin (AG), (2) collagen-containing AG (AGC), and (3) hyaluronic acid-containing AG (AGHA), to recapitulate a native-like environment for human salivary gland (SG) cell expansion and 3D spheroid formation was compared. Although all gels were of mechanical properties comparable to human SG tissue (~11 kPa) and promoted the formation of 3D spheroids, AGHA gels produced larger (>100 cells/spheroid), viable (>93%), proliferative, and well-organized 3D SG spheroids while spatially and temporally maintaining the high expression of key SG proteins (aquaporin-5, NKCC1, ZO-1, α-amylase) for 14 days in culture. Moreover, the spheroids responded to agonist-induced stimulation by increasing α-amylase secretory granules. Here, we propose alternative low-cost, reproducible, and reversible AG-based 3D hydrogels that allow the facile and rapid retrieval of intact, highly viable 3D-SG spheroids.
Humans ; Hydrogels/chemistry* ; Acinar Cells/cytology* ; Spheroids, Cellular/cytology* ; Salivary Glands/cytology* ; Gelatin/chemistry* ; Collagen/chemistry* ; Alginates/chemistry* ; Cell Culture Techniques/methods* ; Hyaluronic Acid/chemistry* ; Cell Proliferation ; Cell Survival ; Cells, Cultured

Organoids are three-dimensional (3D) cellular structures formed through the differentiation and self-organization of pluripotent stem cells or tissue-derived cells, showing considerable potential in the research on disease mechanism, personalized medicine, and developmental biology. However, the development of organoids is limited by the complex composition, batch-to-batch variations, and immunogenicity of basement-membrane matrix in the current culture system, which hinders the clinical translation and in vivo applications of organoids. Hydrogels are highly hydrated 3D polymer network materials, with modifiable mechanical and biochemical properties by engineering, representing an ideal alternative to basement-membrane matrix. This article reviews the research progress in engineered hydrogels with defined composition currently used in organoid culture. We introduce the structural characteristics and engineering design considerations of hydrogels, emphasize the latest research progress and specific application cases, and discuss the future development of these engineered hydrogels, provide valuable insights for the further advancement and optimization of engineered hydrogels for organoid.
Hydrogels/chemistry* ; Organoids/cytology* ; Tissue Engineering/methods* ; Humans ; Animals ; Pluripotent Stem Cells/cytology* ; Cell Culture Techniques, Three Dimensional/methods* ; Tissue Scaffolds

Collagen contains abundant cell binding motifs, which are conducive to adhesion, migration, and differentiation, maintain cell vitality and promote cell proliferation. However, pure collagen hydrogel has some shortcomings such as poor mechanical properties, poor thermal stability and fast degradation. Numerous studies have shown that the properties of collagen can be improved by combining it with natural polysaccharides such as alginate, chitosan, hyaluronic acid and cellulose. In this paper, the research status and biological application fields of four kinds of composite hydrogels, including collagen-alginate composite hydrogels, collagen-chitosan hydrogels, collagen-hyaluronic acid hydrogels and collagen-cellulose hydrogels, were summarized. The common preparation methods of four kinds of composite hydrogels were introduced, and the future development direction of collagen-based composite hydrogels was prospected.
Hydrogels/chemical synthesis* ; Collagen/chemistry* ; Polysaccharides/chemistry* ; Alginates/chemistry* ; Hyaluronic Acid/chemistry* ; Chitosan/chemistry* ; Biocompatible Materials/chemistry* ; Humans ; Tissue Engineering/methods* ; Cellulose/chemistry* ; Tissue Scaffolds