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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2021 · IF 6.953

Photo-crosslinked GelMA/collagen membrane loaded with lysozyme as an antibacterial corneal implant

Xiangjing Yang,Xiaomin Sun,Jia Liu,Yongrui Huang,Yuehai Peng,Yingni Xu,Li Ren

Corneal transplantation is an effective treatment for corneal blindness. However, it brings risk factors for the occurrence of bacterial keratitis, which can affect the repair effect and even lead to transplantation failure. The difficulty in re-epithelialization is also a main problem faced by corneal transplantation. Herein, a collagen-GelMA composite membrane containing lysozyme (CGL) was developed as an antibacterial corneal implant to fill stromal defect and support re-epithelialization. Characterizations of physicochemical properties and in vitro biocompatibility revealed that the composite membranes have proper water content, light transmittance and mechanical strength as well as good biocompatibility. Particularly, the cell adhesion force and adhesion-related genes expression were evaluated and exhibited an improvement after the addition of GelMA. Furthermore, the formed CGL membrane could continuously release lysozyme and exhibited a bactericidal rate of 96% and 64% after 2 h and 72 h, respectively. The results demonstrated that this CGL membrane has promising application in corneal repair.

研究领域: 生物医学工程 · 组织工程 · 眼科学
✓ 已验证 DOI PubMed 高影响因子
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BMC BIOTECHNOLOGY · 2026 · IF 4.8

Periodontal ligament stem cells-loaded photocrosslinking GelMA/PEGDA scaffolds for periodontal bone regeneration

Bei Gao,Jie Yao,Yijie Wang,Chen Chen,Zhen Chai,Wanting Wan,Shiyang Wu,Zhongbo Liu,Rui Zou

Background Matrix stiffness is a key feature of the mechanical microenvironment. Periodontal tissue is a multicomponent structure composed of cementum, periodontal ligament, and alveolar bone, and is essential for the physiological reconstruction and stress of teeth. Simulating the stiffness of periodontal tissue with a biomimetic extracellular matrix is ​​of great significance for regulating cell behavior and tissue repair. In this study, the application of GelMA-PEGDA hybrid hydrogels with different matrix stiffnesses for periodontal bone regeneration was explored. Results In this work, a GelMA‒PEGDA hybrid hydrogel ink was prepared, and the proportion of PEGDA significantly increased the matrix stiffness of the hybrid hydrogel, which had good biocompatibility. In addition, matrix stiffness promoted the osteogenic differentiation and mineralization capacity of periodontal ligament stem cells on the surface of the gels. A high-precision hydrogel scaffold was obtained by introducing a photoinhibitor. The porosity and biocompatibility of the scaffold were good. Conclusions This 3D-printed hydrogel provides a promising strategy for periodontal bone tissue regeneration.

CAS / MDL: 26570-48-9
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Advanced Materials Technologies · 2022 ·Vol. 8 ·期 4 ·2201102 · IF 8.856

One-Step Generation of Porous GelMA Microgels by Droplet-Based Chaotic Advection Effect

Zhongqiao Gan,Haitao Liu,Yaqing Wang,Tingting Tao,Mengqian Zhao,Jianhua Qin

Porous GelMA microgels are promising scaffolds for biomedical research and regenerative medicine due to their special topology, cell-loading capacity, and high biocompatibility. However, the traditional preparation of porous microgels is often limited by some complex postprocessing processes such as freeze-drying and swelling equilibrium. Herein, we present a simple strategy for in situ generation of porous GelMA microgels as cell carriers by integrating the placeholder of polyethylene oxide (PEO) and chaotic advection effect of droplets in microfluidic devices. The device is mainly composed of four functional units, including droplet generation, rapid mixing, photopolymerization, and collection. The strategy allows precise control of the size and porosity of the microgels by changing the flow rates of the continuous and dispersed phases. Furthermore, both human mesenchymal stem cells (hMSCs) and umbilical vein endothelial cells (HUVECs) cultured on the surface of obtained microgels show high cell viability, spreading, and proliferation, which indicate their good biocompatibility and potential as microcarriers for various cell types. The proposed strategy provides a novel approach for the preparation of porous microgels holding promise in tissue engineering and scalable cell expansion.

研究领域: 生物医学工程 · 再生医学 · 组织工程 · 细胞生物学
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS · 2024 · IF 4.9

Preparation and properties of biphasic hydrogels with tunable microstructures

Shenghao Yang,Zhongrui Wang,Yuwen Meng,Xu Wang

Biphasic hydrogels are one of the most important biomaterials in tissue engineering due to their ability to mimic the properties of extracellular matrix. However, the lack of quantitative researches on biphasic hydrogel systems hinder the precise construction of the necessary living conditions for different cells. This fundamental study focuses on a biphasic emulsion hydrogel system consisting of polyethylene glycol diacrylate (PEGDA) and gelatin methacryloyl (GelMA), emphasizing the importance of microstructure in determining the physicochemical properties of biphasic hydrogels. Our approach utilizes a water-in-water (W/W) emulsion system, which is easy to operate and requires no purification steps. By constructing the phase diagram of PEGDA/GelMA biphasic emulsions, we demonstrate that adjusting the volume fractions of the two components results in distinct microstructures, including droplet-based and bicontinuous forms. The composition of biphasic hydrogel significantly influences its mechanical properties, swelling behavior, and biodegradability. Furthermore, the excellent biocompatibility of PEGDA/GelMA biphasic hydrogel system was demonstrated. This study conducts a more in-depth and quantitative study of the PEGDA/GelMA biphasic system. making it a versatile platform for creating precisely biomimetic environments suitable for cell encapsulation and tissue regeneration applications.

研究领域: 组织工程学 · 生物材料科学
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ACS Applied Materials & Interfaces · 2022 · IF 10.383

Microfluidic Preparation of Gelatin Methacryloyl Microgels as Local Drug Delivery Vehicles for Hearing Loss Therapy

Jiali Wang,Chong Wang,Qiao Wang,Zhuohao Zhang,Hui Wang,Shengyi Wang,Zhangcai Chi,Luoran Shang,Wuqing Wang,Yilai Shu

Local drug delivery has become an effective method for disease therapy in fine organs including ears, eyes, and noses. However, the multiple anatomical and physiological barriers, unique clearance pathways, and sensitive perceptions characterizing these organs have led to suboptimal drug delivery efficiency. Here, we developed dexamethasone sodium phosphate-encapsulated gelatin methacryloyl (Dexsp@GelMA) microgel particles, with finely tunable size through well-designed microfluidics, as otic drug delivery vehicles for hearing loss therapy. The release kinetics, encapsulation efficiency, drug loading efficiency, and cytotoxicity of the GelMA microgels with different degrees of methacryloyl substitution were comprehensively studied to optimize the microgel formulation. Compared to bulk hydrogels, Dexsp@GelMA microgels of certain sizes hardly cause air-conducted hearing loss in vivo. Besides, strong adhesion of the microgels on the round window membrane was demonstrated. Moreover, the Dexsp@GelMA microgels, via intratympanic administration, could ameliorate acoustic noise-induced hearing loss and attenuate hair cell loss and synaptic ribbons damage more effectively than Dexsp alone. Our results strongly support the adhesive and intricate microfluidic-derived GelMA microgels as ideal intratympanic delivery vehicles for inner ear disease therapies, which provides new inspiration for microfluidics in drug delivery to the fine organs.

研究领域: 生物医学工程 · 药剂学 · 听力学
✓ 已验证 DOI PubMed 高影响因子
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ACS Biomaterials Science & Engineering · 2026 · IF 6

Engineering a GelMA Hydrogel-Based Biomimetic Endometrium-on-a-Chip for Studying Embryo Implantation

Zhenxing Shi,Juan Liu,Ziyi Ouyang,Lei Guo,Shuyan Wang,Binyang Du,Dan Zhang,Huiquan Wang

Recurrent implantation failure is a critical bottleneck that limits the clinical success rates of assisted reproductive technologies. Existing in vitro implantation models often struggle to balance the conflicting needs of "fluid supply" and "embryo protection": static models lack necessary hydrodynamic stimulation, whereas traditional microfluidic perfusion frequently causes blastocyst damage due to excessive shear stress. Furthermore, most existing scaffold materials fail to mimic the critical dynamic mechanical remodeling of the endometrium during the implantation window. To overcome these limitations, this study constructed a biomimetic endometrium-on-a-chip based on methacryloyl gelatin (GelMA) hydrogels and micropillar arrays, aiming to reconstruct an implantation mechanical microenvironment that closely mimics in vivo conditions. In terms of engineering design, we optimized the micropillar array structure via COMSOL Multiphysics simulation to achieve spatial decoupling of shear stress. This design created a "mechanical sanctuary" for the embryo with shear stress lower than 0.3 dyn/cm2, effectively preventing fluid shear-induced damage while ensuring dynamic nutrient exchange. Regarding the material strategy, this study revealed the concentration-dependent degradation kinetics of GelMA hydrogels. Leveraging their "fast-then-slow" degradation behavior, we recapitulated the mechanical transition of the endometrium, aligning our matrix's softening profile with the physiological shift toward the receptive state characteristic of the implantation window. Biological experiments demonstrated that the GelMA-based hydrogel significantly enhanced the adhesion and zona hatching rates of mouse blastocysts compared to traditional static cultures. Furthermore, by integrating this biomimetic scaffold into a dynamically perfused microfluidic platform, we successfully established a robust in vitro model of mouse embryo implantation.

✓ 已验证 DOI PubMed 高影响因子
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS · 2026 · IF 5.4

Enzyme-Fenton Cascade Reaction for Preparing GelMA Photothermal Antibacterial Hydrogels to Promote Wound Healing

Siyuan Liu,Mengqi Liu,Jia Li,Xingcen Liu,Peiyu Zhang

Gelatin-based hydrogels are promising scaffolds for tissue engineering because of their biocompatibility and adjustable physical and chemical properties. Here, we describe a photothermal hydrogel made from gelatin methacryloyl (GelMA). Unlike UV-crosslinking methods, which can cause light-induced toxicity, gelation in this study occurs through an iron-tannic acid (Fe-TA) metal-phenolic network (MPN) that triggers an enzymatic Fenton cascade reaction. When exposed to glucose in the wound environment, glucose oxidase (GOx) produces hydrogen peroxide (H 2 O 2 ), which reacts with Fe 2+ to create reactive species that cause on-site gelation of GelMA. The resulting hydrogel shows strong biocompatibility and combined photothermal antibacterial effects under light exposure. In addition, L-arginine (L-Arg) is added in a slow-release form to actively support wound healing. This versatile system integrates in situ gelation, antimicrobial effects, and healing promotion, providing a promising approach for advanced wound care.

✓ 已验证 DOI 高影响因子
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2025 · IF 5.6

3D printed GelMA/HAMA based mechanical microenvironment boosted PDAC chemoresistance via NRF2-repressed ferroptosis

Jiashuai Yan,Di Wu,Biwen Zhu,Xiaoqi Guan,Xue Zhang,Yibing Guo,Yuhua Lu

As a highly aggressive solid tumor, pancreatic ductal adenocarcinoma (PDAC) is featured by a conspicuous tumor microenvironment (TME) with abundant extracellular matrix (ECM) deposition, such as collagen and hyaluronic acid (HA). Accompanying with the pathological process, the dense matrix caused stiffen microenvironment, which leads to poor chemotherapy. Therefore, understanding the potential mechanism of mechanical microenvironment on PDAC chemoresistance is of great significance. To this end, 3D printed methacrylated gelatin (GelMA) and hyaluronic acid methacryloyly (HAMA) hydrogel model was fabricated to resemble the mechanical microenvironment of PDAC. The results presented that the PDAC cell lines (MIA-PaCa2 and PANC-1) embedded in the hydrogel were distinctively less sensitive to gemcitabine compared to tissue culture plate (TCP) group. Interestingly, immunofluorescence staining and qRT-PCR assay demonstrated that the NRF2 level was elevated, which further upregulated the downstream effectors, such as SLC7A11 and GPX4. Meanwhile, the GSH concentration and GPX4 activity of hydrogel group were increased, while the lipid peroxidation level was reduced, which indicated that the matrix stiffness microenvironment mediated ferroptosis phenotype. Furthermore, RNA interference experiment elaborated that shNRF2 group showcased significantly enhanced sensitivity to gemcitabine, which demonstrated that the biomimetic microenvironment modulated chemoresistance through ferroptosis. All in all, the 3D printed model may serve as a new platform for illustrating the underlying mechanism of the TME induced chemoresistance, and also proposed a novel therapeutic strategy for PDAC through NRF2 inhibition, which effectively promotes ferroptosis to overcome chemoresistance.

CAS / MDL: 9002-93-1
研究领域: 肿瘤学 · 细胞生物学 · 生物医学工程
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MACROMOLECULAR BIOSCIENCE · 2022 ·Vol. 22 ·期 10 ·2200208 · IF 5.859

3D Printing GelMA/PVA Interpenetrating Polymer Networks Scaffolds Mediated with CuO Nanoparticles for Angiogenesis

Qingxi Hu,Runsheng Lu,Suihong Liu,Yakui Liu,Yan Gu,Haiguang Zhang

Biocompatible hydrogels have been considered one of the most well-known and promising in various materials used in the fabrication of tissue-engineering scaffolds. Although considerable progress has been made in recent decades, many limitations remain, such as poor mechanical and degradation properties of biomaterials. In addition, vascularization of tissue-engineering scaffold is an enduring challenge, which limited the fabrication and application of scaffold with clinically relevant dimension. To cover these challenges, in this work, a novel nanocomposite interpenetrating polymer networks (IPN) hydrogel scaffold consists of methacrylated gelatin (GelMA), poly(vinyl alcohol) (PVA), and copper oxide nanoparticles (CuONPs) is fabricated by extrusion-based 3D printing. A series of physiochemical and biological characterizations of the nanocomposite GelMA/PVA scaffolds are performed. Results showed that the mechanical and degradation properties of the nanocomposite GelMA/PVA scaffolds are obviously improved compared to GelMA scaffolds with single network. In vitro cell experiments and chick embryo angiogenesis (CEA) assay confirmed good cytocompatibility of the fabricated scaffold and its potential to promote cell migration and angiogenesis. In conclusion, altogether the results demonstrated that GelMA/PVA IPN scaffolds modified with CuONPs have great potential for fabrication of volumetric scaffolds and promote angiogenesis during tissue growth and repair.

研究领域: 材料科学 · 生物材料 · 组织工程 · 纳米技术 · 生物医学工程
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BIOMACROMOLECULES · 2024 · IF 5.5

Gelatin Methacryloyl (GelMA)-Based Biomaterial Inks: Process Science for 3D/4D Printing and Current Status

Soumitra Das,Jeyapriya Thimukonda Jegadeesan,Bikramjit Basu

Tissue engineering for injured tissue replacement and regeneration has been a subject of investigation over the last 30 years, and there has been considerable interest in using additive manufacturing to achieve these goals. Despite such efforts, many key questions remain unanswered, particularly in the area of biomaterial selection for these applications as well as quantitative understanding of the process science. The strategic utilization of biological macromolecules provides a versatile approach to meet diverse requirements in 3D printing, such as printability, buildability, and biocompatibility. These molecules play a pivotal role in both physical and chemical cross-linking processes throughout the biofabrication, contributing significantly to the overall success of the 3D printing process. Among the several bioprintable materials, gelatin methacryloyl (GelMA) has been widely utilized for diverse tissue engineering applications, with some degree of success. In this context, this review will discuss the key bioengineering approaches to identify the gelation and cross-linking strategies that are appropriate to control the rheology, printability, and buildability of biomaterial inks. This review will focus on the GelMA as the structural (scaffold) biomaterial for different tissues and as a potential carrier vehicle for the transport of living cells as well as their maintenance and viability in the physiological system. Recognizing the importance of printability toward shape fidelity and biophysical properties, a major focus in this review has been to discuss the qualitative and quantitative impact of the key factors, including microrheological, viscoelastic, gelation, shear thinning properties of biomaterial inks, and printing parameters, in particular, reference to 3D extrusion printing of GelMA-based biomaterial inks. Specifically, we emphasize the different possibilities to regulate mechanical, swelling, biodegradation, and cellular functionalities of GelMA-based bio(material) inks, by hybridization techniques, including different synthetic and natural biopolymers, inorganic nanofillers, and microcarriers. At the close, the potential possibility of the integration of experimental data sets and artificial intelligence/machine learning approaches is emphasized to predict the printability, shape fidelity, or biophysical properties of GelMA bio(material) inks for clinically relevant tissues.

研究领域: 生物医学工程 · 材料科学 · 再生医学
✓ 已验证 DOI PubMed 高影响因子
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CHEMICAL ENGINEERING JOURNAL · 2026 · IF 12.5

Injectable photo-crosslinkable GelMA hydrogel incorporating quercetin@Zif-8 nanocarriers for osteoimmunomodulation and bone regeneration

Qing Gao,Wanshuang Zhang,Yi Li,Li Lin,Wen Jin,Jiayin Qiu,Kai Xie,Xianfa Yuan

Injectable Que@ZIF-8/Gel hydrogel offers structural support and sustained quercetin release. • The hydrogel demonstrates pro-osteogenic, pro-angiogenic, antioxidant, and immunomodulatory effects. • It enables effective bone regeneration in rat calvarial defects, showing clinical promise. Effective bone regeneration demands biomaterials that provide mechanical support and actively orchestrate osteogenesis, angiogenesis, and immune modulation. Here, we engineered an injectable, photo-crosslinkable hydrogel by integrating quercetin-loaded Zif-8 nanoparticles within a GelMA matrix (Que@Zif-8/Gel). This composite exhibited tunable mechanics, sustained drug release, and favorable physicochemical properties. In vitro, Que@Zif-8/Gel supported BMSC adhesion, proliferation, and osteogenic differentiation without cytotoxic or hemolytic effects. It also enhanced endothelial migration and tube formation, attenuated LPS-induced oxidative stress, and directed macrophages toward a reparative M2 phenotype characterized by elevated IL-10 and reduced TNF-α. In a rat calvarial defect model, Que@Zif-8/Gel treatment promoted substantial new bone formation, improved mineral density and trabecular structure, and upregulated osteogenic markers including COL-1 and OPN. In summary, these findings establish Que@Zif-8/Gel as a multifunctional platform that integrates structural reinforcement with angiogenic, antioxidant, and immunoregulatory activities, offering strong translational potential for vascularized bone regeneration.

✓ 已验证 DOI 高影响因子
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Journal of Materials Chemistry B · 2025 · IF 5.7

Angiogenesis-Osteogenesis Coupling and Immunomodulatory CGRP@Nano MOF-Loaded CMCS/GelMA Hydrogel for Bone Regeneration

Rong Luo,Zhao Chen,Man Zhe,Wenting Wu,Yuzhen Xiao,Jiabao Jiang,Hao Liu,Ming Liu,Fei Xing

The management of bone defects poses a significant challenge for clinicians, necessitating effective strategies to regulate immune inflammation, angiogenesis, and osteogenic differentiation for successful bone regeneration. In this study, we developed a novel hydrogel composed of carboxymethyl chitosan (CMCS) and gelatin methacryloyl (GelMA) designed for the sustained release of the bioactive component calcitonin gene-related peptide (CGRP) and zeolitic imidazolate framework-8 (ZIF-8). CGRP was initially encapsulated within ZIF-8 and subsequently integrated into the CMCS/GelMA hydrogel matrix. In vitro evaluations revealed that the hydrogel exhibited exceptional biocompatibility and antimicrobial properties, effectively promoting osteogenesis and angiogenesis while modulating M2 macrophage polarization. Furthermore, in vivo assessments indicated that the CGRP@MOF/CG hydrogel significantly regulated the local immune microenvironment and accelerated the healing of cranial defects in rat models. This study provides valuable references for the design and fabrication of multifunctional materials for enhancing bone regeneration.

研究领域: 生物材料学 · 组织工程学 · 再生医学
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