1.Anti-tumor effect of metal ion-mediated natural small molecules carrier-free hydrogel combined with CDT/PDT.
Wen-Min PI ; Gen LI ; Xin-Ru TAN ; Zhi-Xia WANG ; Xiao-Yu LIN ; Hai-Ling QIU ; Fu-Hao CHU ; Bo WANG ; Peng-Long WANG
China Journal of Chinese Materia Medica 2025;50(7):1770-1780
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
2.Research progress of bioactive scaffolds in repair and regeneration of osteoporotic bone defects.
Yuangang WU ; Kaibo SUN ; Yi ZENG ; Bin SHEN
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(1):100-105
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
3.Application and progress of intelligent responsive hydrogels in articular cartilage injury repair.
Qingyu XU ; Baojian ZHANG ; Hongri LI ; Chengri LIU ; Shuhao BI ; Zhixiang YANG ; Yanqun LIU
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(2):250-256
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*
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Humans
;
Animals
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Chondrocytes/cytology*
;
Biocompatible Materials/chemistry*
;
Tissue Scaffolds/chemistry*
4.Research progress of hydrogel-based growth factors for treatment of intervertebral disc degeneration.
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(11):1491-1497
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*
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Hydrogels/chemistry*
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Humans
;
Intercellular Signaling Peptides and Proteins/administration & dosage*
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Biocompatible Materials/chemistry*
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Animals
;
Tissue Engineering/methods*
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Cell Proliferation/drug effects*
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Drug Delivery Systems
5.Application and advances of exosome-hydrogel system in wound healing.
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(12):1615-1622
OBJECTIVE:
To review the recent advances in the application of exosome-hydrogel system for wound healing.
METHODS:
A wide range of recent domestic and international studies were reviewed to systematically outline the roles and mechanisms of exosomes, hydrogels, and their composite system in promoting wound repair.
RESULTS:
Wound healing is a complex and finely regulated process. Traditional therapies lack targeted regulation of key mechanisms such as inflammation control, angiogenesis, collagen remodeling, and re-epithelialization. The exosome-hydrogel system enhances wound repair through targeted modulation of these mechanisms and provides effective protection against bacterial infection, hypoxia, excessive oxidative stress, and hyperglycemic microenvironments.
CONCLUSION
The exosome-hydrogel system represents an emerging approach for chronic wound repair and skin regeneration, potentially overcoming the inherent limitations of traditional therapies. Nevertheless, the lack of standardized preparation methods and dosing protocols calls for further optimization.
Wound Healing
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Humans
;
Hydrogels
;
Exosomes
;
Skin/injuries*
;
Animals
;
Re-Epithelialization
6.Human epidermal growth factor gel for pin tract infection following halo-pelvic ring traction procedure in patients with severe spinal deformity.
Yu-Liang LOU ; Feng HONG ; Can-Feng WANG ; Hui FEI ; Wei-Bin DU ; Ren-Fu QUAN
China Journal of Orthopaedics and Traumatology 2025;38(8):816-821
OBJECTIVE:
To explore the efficacy and safety of human epidermal growth factor gel in the treatment of pin tract infections after surgery in patients with severe spinal deformity.
METHODS:
A retrospective case-control study was conducted to analyze the clinical data of 26 patients with pin tract infections after skull-pelvic ring traction for severe spinal deformity admitted from February 2019 to May 2022. Among them, 11 were male and 15 were female;the age ranged from 18 to 31 years, with an average of (24.1±4.3) years;the Cobb angle ranged 80.3° to 120.7°, with an average of (88.6±10.2)°;there were 52 iliac traction pins, 104 pin tract openings, and 38 pin tract infections. According to the Checketts-Otterbum classification, there were 11 infections of gradeⅠ, 13 infections of gradeⅡ, 10 infections of grade Ⅲ, and 4 infections of grade Ⅳ. The patients were divided into the conventional dressing change group (13 cases) and the growth factor group (13 cases) by coin flipping. Clinical efficacy was evaluated by recording the visual analogue scale(VAS) score during dressing change, duration of dressing change, cost of dressing change, positive rate of bacterial culture, wound improvement rate, and wound improvement time.
RESULTS:
There were no statistically significant differences in VAS or duration of dressing change between the two groups (P>0.05). The cost of dressing change was (800.0±59.5) yuan in the conventional dressing change group and (1 179.5±80.9) yuan in the growth factor group, with a statistically significant difference (P<0.05). There was no statistically significant difference in the positive rate of bacterial culture between the two groups (P>0.05). In the conventional dressing change group, within 20 pin tract infections, 2 infections achieved wound healing, 7 infections showed improvement, and 11 infections were ineffective;in the growth factor group, within 18 pin tract infections 5 infections achieved wound healing, 8 infections showed improvement, and 5 infections were ineffective, with a statistically significant difference between the two groups (P<0.05). The wound healing time was (22.8±4.9) days in the conventional dressing change group and (14.2±2.5) days in the growth factor group, with a statistically significant difference (P<0.05). No complications occurred in either group.
CONCLUSION
The application of human epidermal growth factor gel in the treatment of pin tract infections after skull-pelvic ring surgery in patients with severe spinal deformity is easy to operate, does not increase patient pain, and has significant efficacy. It shortens wound healing time, effectively promotes wound healing, and has good safety and high cost-effectiveness.
Humans
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Male
;
Female
;
Adult
;
Adolescent
;
Retrospective Studies
;
Case-Control Studies
;
Young Adult
;
Epidermal Growth Factor/therapeutic use*
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Traction/adverse effects*
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Gels
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Bone Nails/adverse effects*
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Surgical Wound Infection/drug therapy*
7.Biomaterials of different sizes for enhanced adoptive cell transfer therapy in solid tumors.
Jiaxin CHEN ; Rui LIU ; Yingqi TANG ; Chenggen QIAN
Journal of Zhejiang University. Medical sciences 2025;54(4):469-478
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
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Neoplasms/therapy*
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Biocompatible Materials/chemistry*
;
Immunotherapy, Adoptive/methods*
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Nanoparticles
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Hydrogels
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Adoptive Transfer/methods*
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Animals
8.Advances in hydrogel drug delivery systems for myocardial infarction treatment.
Jia YANG ; Zheng ZHOU ; Xiahong XIE ; Mingzhou YE
Journal of Zhejiang University. Medical sciences 2025;54(4):455-468
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*
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Myocardial Infarction/drug therapy*
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Humans
;
Drug Delivery Systems/methods*
;
Biocompatible Materials
;
Drug Carriers
9.Microfluidic photo-curing fabrication of silk fibroin/hyaluronic acid composite microsphere hydrogels.
Ruyue WANG ; Yunlu CHEN ; Chenqi WU ; Shujing LI ; Zhenjie LIU ; Feng CHEN
Journal of Zhejiang University. Medical sciences 2025;54(4):434-445
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
10.Current Research Status of Biomedical Hydrogel and Challenges and Opportunities in Clinical Translation.
Huan LIAN ; Li LIU ; Linnan KE
Chinese Journal of Medical Instrumentation 2025;49(5):520-526
As representatives of the third generation of biomedical materials, hydrogels exhibit revolutionary potential in tissue engineering, precision drug delivery, and smart medical devices due to their ability to construct bionic microenvironments. However, the clinical translation of hydrogels is still limited by multidimensional challenges, including biocompatibility, scalable production, and regulatory complexity. This paper systematically reviews the design innovations, functionalization strategies, and translational bottlenecks of hydrogel materials, integrates the latest technological trends, such as 4D printing and AI-driven design, and proposes a collaborative optimization pathway encompassing materials, technology, clinical applications, and policy. By introducing local Chinese innovation cases and monitoring scientific advancements, this study offers solutions that possess both academic significance and practical guidance for the clinical translation of hydrogels.
Hydrogels
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Tissue Engineering
;
Translational Research, Biomedical
;
Biocompatible Materials
;
Humans
;
Drug Delivery Systems

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