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Materials Today Communications · 2025 · IF 4.5

3D-printed multilayer GelMA-PVA dual-network hydrogels with gradient andrographolide loading for antimicrobial wound healing: Fabrication, characterization, and in vitro evaluation

Ding Shen,Jingbin Hao,Siyu Liu,Md Thowfiqure Rahman,Shuaihang Wang,Sameer Hussain Jhatial

Chronic wounds are often aggravated by bacterial infection and prolonged inflammation, presenting major challenges in clinical wound management. To address these issues, a novel 3D-printed multilayer hydrogel was developed, based on a GelMA-PVA dual-network system incorporating graded concentrations of andrographolide (Andro), a phytochemical with proven antibacterial and anti-inflammatory activity. The GelMA component was photocrosslinked, while the PVA network was physically crosslinked via freeze–thaw cycles, forming a robust interpenetrating structure. The hydrogels were characteriazed using FTIR, XPS, SEM, mechanical testing, swelling analysis, and in vitro release and antibacterial assays. The multilayer patches demonstrated tunable swelling capacity (up to 1938 %), excellent tensile strength (up to 46.7 kPa) and compressive strength (up to 94.3 kPa), and a sustained drug release profile. In vitro studies confirmed enhanced L929 fibroblast proliferation and significant antibacterial activity against E. coli and S. aureus , particularly in the gradient Andro-loaded groups. These results suggest that the 3D-printed GelMA-PVA-Andro patches are promising candidates for advanced wound dressings with integrated mechanical, biological, and pharmaceutical functionalities.

CAS / MDL: 9002-89-5
研究领域: 生物材料 · 组织工程 · 药剂学 · 生物医学工程 · 微生物学 · 材料科学
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CERAMICS INTERNATIONAL · 2023 · IF 5.2

Combined treatment using novel multifunctional MAu-GelMA hydrogel loaded with neural stem cells and electrical stimulation promotes functional recovery from spinal cord injury

Weijian Kong,Yinlong Zhao,Yang Xiaoyu,Jing Chen,Yihang Chen,Zhengyang Zhao,Xiaonan Chen,Feng Wang,Chuan Fu

The massive death of nerve cells and the inflammatory microenvironment resulting from the release of reactive oxygen species after spinal cord injury (SCI) hinders the subsequent reconstruction of motor function. Owing to complex pathological changes, combination therapy is a potential new way to treat SCI. In this study, a novel multifunctional hydrogel containing an MXene-Au complex was constructed, and neural stem cells (NSCs) loaded in the hydrogel were combined with electrical stimulation to promote the recovery of motor function after SCI in rats. The constructed MAu-GelMA hydrogel had good reactive oxygen species-scavenging ability, electrical conductivity , and antibacterial ability. Simultaneously, electrical stimulation promoted the proliferation and differentiation of NSCs into nerve cells and promoted the establishment of synaptic connections between neurons. In the rat SCI model, combined treatment using MAu-GelMA hydrogel carrying NSCs and electrical stimulation reduced the formation of cavities and glial scars, enhanced neuronal differentiation and myelin regeneration of NSCs in the injured area, and promoted the recovery of motor function after SCI. In conclusion, in this study, we constructed a novel multifunctional hydrogel capable of carrying NSCs, which upon combining with electrical stimulation during treatment, effectively promoted the recovery of motor function in rats with SCI, thereby providing a new combination therapy strategy for SCI.

CAS / MDL: 13453-07-1
研究领域: 神经科学 · 生物材料 · 再生医学 · 组织工程
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Frontiers in Bioengineering and Biotechnology · 2020 · IF 3.644

Production and Characterization of an Integrated Multi-Layer 3D Printed PLGA/GelMA Scaffold Aimed for Bile Duct Restoration and Detection

Xiang Yang,Wang Weijia,Gao Yuanhui,Zhang Jianquan,Zhang Jing,Bai Zhiming,Zhang Shufang,Yang Yijun

We successfully fabricated artificial bile duct via 3D printing technique which was composed of poly (lactic-co-glycolic acid) (PLGA) and gelatin methacrylate (GelMA). The PLGA-inner layer provided sufficient strength to support the bile duct contraction, the GelMA-outer layer possessed good biocompatibility to provide a good living environment for the cells. Moreover, IKVAV laminin peptide (Ile-Lys-Val-Ala-Val) and ultrasmall superparamagnetic iron oxide (USPIO) were used to regulate scaffold cell adhesion and magnetic resonance imaging (MRI) detection, respectively. After BMSCs co-culture with IKVAV at a certain concentration, the survival rate and adhesion of BMSCs was increased obviously. Meanwhile, the fabricated scaffold exhibited the tensile modulus in the range of 17.19 – 29.05 MPa and the compressive modulus in the range of 0.042 – 0.066 MPa, which could meet the needs of human implantation. In an animal experiment in vivo pig bile duct regeneration, PLGA/GelMA/IKVAV/USPIO duct conduits could promote bile duct regeneration and enhance cytokeratin 19 (CK19) expression. In summary, the composite bile duct scaffold with excellent MRI imaging function and biocompatibility could be used to develop bioactive artificial bile ducts.

CAS / MDL: 9000-70-8 760-93-0
研究领域: 生物医学工程 · 组织工程 · 再生医学 · 医学影像
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Bioactive Materials · 2022 · IF 16.874

Hydrogel platform with tunable stiffness based on magnetic nanoparticles cross-linked GelMA for cartilage regeneration and its intrinsic biomechanism

Chenchen Zhou,Chunli Wang,Kang Xu,Zhixing Niu,Shujuan Zou,Demao Zhang,Zhiyong Qian,Jinfeng Liao,Jing Xie

Cartilage injury affects numerous individuals, but the efficient repair of damaged cartilage is still a problem in clinic. Hydrogel is a potent scaffold candidate for tissue regeneration, but it remains a big challenge to improve its mechanical property and figure out the interaction of chondrocytes and stiffness. Herein, a novel hybrid hydrogel with tunable stiffness was fabricated based on methacrylated gelatin (GelMA) and iron oxide nanoparticles (Fe 2 O 3 ) through chemical bonding. The stiffness of Fe 2 O 3 /GelMA hybrid hydrogel was controlled by adjusting the concentration of magnetic nanoparticles. The hydrogel platform with tunable stiffness modulated its cellular properties including cell morphology, microfilaments and Young's modulus of chondrocytes. Interestingly, Fe 2 O 3 /GelMA hybrid hydrogel promoted oxidative phosphorylation of mitochondria and facilitated catabolism of lipids in chondrocytes. As a result, more ATP and metabolic materials generated for cellular physiological activities and organelle component replacements in hybrid hydrogel group compared to pure GelMA hydrogel. Furthermore, implantation of Fe 2 O 3 /GelMA hybrid hydrogel in the cartilage defect rat model verified its remodeling potential. This study provides a deep understanding of the bio-mechanism of Fe 2 O 3 /GelMA hybrid hydrogel interaction with chondrocytes and indicates the hydrogel platform for further application in tissue engineering.

研究领域: 生物材料 · 组织工程 · 生物力学 · 再生医学
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CHEMICAL ENGINEERING JOURNAL · 2023 · IF 15.1

Bioactive wound dressing based on decellularized tendon and GelMA with incorporation of PDA-loaded asiaticoside nanoparticles for scarless wound healing

Shuang Liu,Yingsong Zhao,Ming Li,Lei Nie,Qianqian Wei,Oseweuba Valentine Okoro,Hafez Jafari,Siyuan Wang,Jun Deng,Jianghai Chen,Amin Shavandi,Lihong Fan

In this study, bioactive composite hydrogels were created using the decellularized extracellular matrix (ECM), GelMA, and Polydopamine-loaded Asiaticoside (AC@PDA) nanoparticles for use as wound dressings that could promote healing. A decellularization method was used to obtain ECM from porcine Achilles tendon tissue. AC@PDA nanoparticles were then synthesized and found to have a uniform spherical structure with good cytocompatibility, particularly when compared to PDA nanoparticles alone. The mechanical properties of the bioactive composite hydrogels showed good elasticity and shape recovery after compression, with a slight decrease in compressive strength due to the addition of nanoparticles. The formation of interpenetrating networks through the use of EDC/NHS was also found to improve the mechanical properties and moisture retention of the hydrogels. The PDA/ECM-G and AC@PDA/ECM-G hydrogels showed higher water absorption capacity and similar moist retention capacity to the ECM-G hydrogel. The microstructure of the hydrogels was observed through SEM, with the ECM-G hydrogel showing a dense and compact structure, while the PDA/ECM-G and AC@PDA/ECM-G hydrogels displayed a more porous and interconnected structure due to the presence of nanoparticles. In vitro cytotoxicity tests on human skin fibroblasts showed good biocompatibility for all hydrogels. The in vivo wound healing performance of the hydrogels was also tested on a full-thickness excisional wound model in mice, with the AC@PDA/ECM-G hydrogel showing the fastest wound closure without scarring and the highest-formed hair follicles. The AC@PDA/ECM-G hydrogel had the best performance in promoting wound healing. These results suggest that the bioactive hydrogel has the potential for use as a wound dressing.

研究领域: 生物材料 · 组织工程 · 伤口愈合 · 纳米技术 · 生物医学工程
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ACS Applied Materials & Interfaces · 2023 · IF 9.5

Layered GelMA/PEGDA Hydrogel Microneedle Patch as an Intradermal Delivery System for Hypertrophic Scar Treatment

Zhijing Chen,Xiaole Hu,Zhengjie Lin,Haoran Mao,Zhen Qiu,Kerong Xiang,Tiancheng Ke,Lihua Li,Lu Lu,Liling Xiao

Hypertrophic scar (HS) is an unfavorable skin disorder that typically develops after trauma, burn injury, or surgical procedures and causes numerous physical and psychological issues in patients. Currently, intralesional multi-injection of corticosteroid, particularly compound betamethasone (CB), is one of the most prevalent treatments for HS. However, injection administration could result in severe pain and dose-related side effects. Additionally, the vacuum therapeutic efficacy of this treatment relies on the level of expertise of the healthcare professional. To overcome the limitations of conventional injections, a new method that is convenient, painless, and self-administrable is urgently required. In this study, we developed a methacrylate gelatin (GelMA)/polyethylene glycol diacrylate (PEGDA) double-network hydrogel microneedle patch loaded with CB (CB-HMNP) as an intradermal delivery system for HS treatment. The double-network structure conferred the CB-HMNP with sufficient mechanical properties to successfully penetrate scar tissue while also helping to regulate the drug’s sustained release rate. Subsequently, we confirmed that the CB-HMNP had a pronounced inhibitory effect on human HS fibroblasts (hHSFs), whereas drug-free HMNPs had no effect on hHSFs, indicating its high biocompatibility. In order to assess the therapeutic efficacy of CB-HMNPs, HS models of New Zealand rabbit ears were developed. The administration of CB-HMNP three times significantly decreased the scar elevation index (SEI), collagen I/III, and transforming growth factor-β1 (TGF-β1) protein. Therefore, the CB-HMNP may offer an administration pathway for the treatment of HS that is less painful, more convenient, less invasive, and sustain-released.

CAS / MDL: 760-93-0 26570-48-9
研究领域: 药学 · 材料科学 · 生物医学工程 · 皮肤科
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Bioactive Materials · 2020 · IF 8.724

Neuro-regenerative imidazole-functionalized GelMA hydrogel loaded with hAMSC and SDF-1α promote stem cell differentiation and repair focal brain injury

Yantao Zheng,Gang Wu,Limei Chen,Ying Zhang,Yuwei Luo,Yong Zheng,Fengjun Hu,Tymor Forouzanfar,Haiyan Lin,Bin Liu

Brain tissues that are severely damaged by traumatic brain injury (TBI) is hardly regenerated, which leads to a cavity or a repair with glial scarring. Stem-cell therapy is one viable option to treat TBI-caused brain tissue damage, whose use is, whereas, limited by the low survival rate and differentiation efficiency of stem cells. To approach this problem, we developed an injectable hydrogel using imidazole groups-modified gelatin methacrylate (GelMA-imid). In addition, polydopamine (PDA) nanoparticles were used as carrier for stromal-cell derived factor-1 (SDF-1α). GelMA-imid hydrogel loaded with [email protected] α nanoparticles and human amniotic mesenchymal stromal cells (hAMSCs) were injected into the damaged area in an in-vivo cryogenic injury model in rats. The hydrogel had low module and its average pore size was 204.61 ± 41.41 nm, which were suitable for the migration, proliferation and differentiation of stem cells. In-vitro cell scratch and differentiation assays showed that the imidazole groups and SDF-1α could promote the migration of hAMSCs to injury site and their differentiation into nerve cells. The highest amount of nissl body was detected in the group of GelMA-imid/SDF-1α/hAMSCs hydrogel in the in-vivo model. Additionally, histological analysis showed that GelMA-imid/SDF-1α/hAMSCs hydrogel could facilitate the regeneration of regenerate endogenous nerve cells. In summary, the GelMA-imid/SDF-1α/hAMSCs hydrogel promoted homing and differentiation of hAMSCs into nerve cells, and showed great application potential for the physiological recovery of TBI.

研究领域: 神经科学 · 干细胞疗法 · 生物材料 · 再生医学
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BIOMATERIALS · 2025 · IF 12.9

A Nerve Conduit Optimizing the Microenvironment for Neurorepair in Long-Segment Nerve Injury Using Silk Fibroin-MXene Conductive Nerve Guide and IGF-1/GelMA Hydrogel

Lan Zeng,Kang Ma,Ying Huang,Bingqing Liao,Luyao Zhong,Yue Zhao,Yongling Lu,Kai Xu,Shi Wang,Ning Mu,Yaning Shi,Chuanyan Yang,Xianyong Fu,Rong Hu,Hua Feng,Qiang Zhang,Xiaoming Wang,Tunan Chen

Long-segment peripheral nerve injury (PNI) represents a significant global health challenge, often leading to sensory and motor deficits, neuropathic pain, and secondary complications. Early reconnection of injured nerves is essential for preserving function and minimizing sequelae. In this study, we present a novel Silk Fibroin-MXene (SF-MXene) pIGF1 GelMA Hydrogel Nerve Conduit as an effective solution to optimize the bio-electrical and cellular microenvironment, thereby accelerating nerve regeneration. Unlike standalone plasmid Insulin-like Growth Factor-1 (pIGF1) releasing conduits, which disrupt growth direction and attract non-neuronal repair cells that obstruct nerve elongation, this advanced conduit enhances directional nerve growth and myelination while facilitating efficient electrical signal transmission in PNI rats. In this multifunctional NGC, pIGF1 optimizes the cellular microenvironment by promoting Schwann cell proliferation and migration, while the conductive SF-MXene NGC supports spatially ordered distribution and accelerates nerve elongation. Additionally, the conduit sustains long-term RANKL upregulation, activating NF-κB signaling to drive Schwann cell differentiation into myelinating subtypes, thereby promoting efficient and durable myelination of regenerated nerves and facilitating effective electrical signal transmission. These findings underscore the potential of the Silk-MXene+pIGF1 Nerve Conduit as a promising strategy for long-segment nerve injury repair, with strong implications for future clinical applications.

CAS / MDL: 497-19-8 7550-35-8
研究领域: 生物医学工程 · 神经组织工程 · 再生医学 · 生物材料 · 神经科学
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Materials Today Bio · 2023 · IF 8.2

Advantages of photo-curable collagen-based cell-laden bioinks compared to methacrylated gelatin (GelMA) in digital light processing (DLP) and extrusion bioprinting

Huimin Shi,Yang Li,Kailei Xu,Jun Yin

The development of cell-laden bioinks that possess high biocompatibility and printability is crucial in the field of bioprinting for the creation of cell-embedded tissue engineering scaffolds. As widely known, methacrylated gelatin (GelMA) is one of the most commonly used photo-crosslinkable bioink for cell-laden bioprinting with different printing methods, but GelMA is the derivative of gelatin, so it loses the unique triple-helix molecular structure of collagen and may not be able to successfully activate the cellular pathways or facilitate cell-matrix interaction as effectively as collagen. Recently, methacrylated collagen (CMA) was developed to be an alternative photocrosslinkable bioink with a good bioactivity, but its low printability and biocompatibility limited that application in tissue engineering. In this study, the synthetic process for CMA was improved by synthesizing under 4 °C and using acidic aqueous solution as solvent. Our CMA bioinks were demonstrated a similar printability as GelMA in extrusion bioprinting, while a better formability in digital light processing (DLP). To further analyze the bioactive properties, CMA bioinks were encapsulated with Schwann cells (SCs) and bone mesenchymal stem cells (BMSCs) for printing. SCs-laden CMA bioinks had a significantly higher proliferation rate and expression of neural stem cell-associated genes than GelMA in DLP bioprinting. While, BMSCs-laden CMA bioinks demonstrated >95% cellular viability, better cell spreading and higher expression of osteogenesis-related genes than that of GelMA. Overall, we speculate that the CMA-based bioink developed in this study could be potential bioinks for 3D cell-laden bioprinting in the future.

研究领域: 组织工程 · 生物打印 · 生物材料 · 细胞生物学
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JOURNAL OF NANOBIOTECHNOLOGY · 2024 ·Vol. 22 ·期 1 ·1-29 · IF 10.6

A novel spherical GelMA-HAMA hydrogel encapsulating APET×2 polypeptide and CFIm25-targeting sgRNA for immune microenvironment modulation and nucleus pulposus regeneration in intervertebral discs

Yu Xiao-Jun,Zhao Yuan-Ting,Abudouaini Haimiti,Zou Peng,Li Tian-Qi,Bai Xiao-Fan,Wang Shan-Xi,Guan Jian-Bin,Li Meng-wei,Wang Xiao-dong,Wang Ying-guang,Hao Ding-Jun

Methods Single-cell transcriptomics and high-throughput transcriptomics were used to screen factors significantly correlated with intervertebral disc degeneration (IDD). Expression changes of CFIm25 were determined via RT-qPCR and Western blot. NP cells were isolated from mouse intervertebral discs and induced to degrade with TNF-α and IL-1β. CFIm25 was knocked out using CRISPR-Cas9, and CFIm25 knockout and overexpressing nucleus pulposus (NP) cell lines were generated through lentiviral transfection. Proteoglycan expression, protein expression, inflammatory factor expression, cell viability, proliferation, migration, gene expression, and protein expression were analyzed using various assays (alcian blue staining, immunofluorescence, ELISA, CCK-8, EDU labeling, transwell migration, scratch assay, RT-qPCR, Western blot). The GelMA-HAMA hydrogel loaded with APET×2 polypeptide and sgRNA was designed, and its effects on NP regeneration were assessed through in vitro and mouse model experiments. The progression of IDD in mice was evaluated using X-ray, H&E staining, and Safranin O-Fast Green staining. Immunohistochemistry was performed to determine protein expression in NP tissue. Proteomic analysis combined with in vitro and in vivo experiments was conducted to elucidate the mechanisms of hydrogel action. Results CFIm25 was upregulated in IDD NP tissue and significantly correlated with disease progression. Inhibition of CFIm25 improved NP cell degeneration, enhanced cell proliferation, and migration. The hydrogel effectively knocked down CFIm25 expression, improved NP cell degeneration, promoted cell proliferation and migration, and mitigated IDD progression in a mouse model. The hydrogel inhibited inflammatory factor expression (IL-6, iNOS, IL-1β, TNF-α) by targeting the p38/NF-κB signaling pathway, increased collagen COLII and proteoglycan Aggrecan expression, and suppressed NP degeneration-related factors (COX-2, MMP-3). Conclusion The study highlighted the crucial role of CFIm25 in IDD and introduced a promising therapeutic strategy using a porous spherical GelMA-HAMA hydrogel loaded with APET×2 polypeptide and sgRNA. This innovative approach offers new possibilities for treating degenerated intervertebral discs. Graphical Abstract Molecular mechanism of GCA targeting CFIm25 in NP cells to promote regeneration of degenerated intervertebral disc NP

CAS / MDL: 85073-19-4
研究领域: 生物医学工程 · 再生医学 · 组织工程 · 分子生物学 · 细胞生物学 · 骨科
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Nanoscale · 2023 ·Vol. 15 ·期 34 ·14189-14204 · IF 6.7

Novel PVAMA/GelMA aerogels prepared by liquid-phase collection of photoinitiated polymerisation: injectable and flowable low-density 3D scaffolds for bone regeneration

Manxuan Liu,Yihan Sun,Lijun Liu,Zhiying Zhang,Maierhaba Aimaijiang,Lu Zhang,Sezhen Quni,Minghui Li,Xiuyu Liu,Daowei Li,Junhu Zhang,Yanmin Zhou

Nanofibrous scaffolds, which are morphologically/structurally similar to native extracellular matrix, are ideal biomaterials for tissue engineering and regenerative medicine. However, the use of traditional electrospinning techniques to produce three-dimensional (3D) nanofibrous scaffolds with desired structural properties presents difficulty. To address this challenge, we prepared a novel liquid–phase-collected photoinitiated polymerised aerogel 3D scaffold (LPPI-AG) using the thermally induced (nanofiber) self-aggregation method after liquid-phase electrospinning of the hydroxyapatite-doped methacrylated polyvinyl alcohol/methacrylated gelatine solution obtained by photoinitiated polymerisation. The fabricated aerogel scaffolds had a high porosity of approximately 99.01% ± 0.40% and an interconnected network structure with pore sizes ranging from submicron to ∼300 μm. The new aerogel rapidly became flowable when exposed to a solution, and it can fill gaps and repair gap edges effectively and be loaded with nutrients and growth factors that promote bone growth for bone tissue engineering. LPPI-AG scaffolds can considerably promote osteogenic differentiation of bone marrow mesenchymal stem cells in vitro. Furthermore, in vivo studies showed that the LPPI-AG scaffold significantly promoted bone formation in a mouse model of critical-size calvarial defects.

研究领域: 组织工程 · 再生医学 · 生物材料 · 生物医学工程 · 骨再生
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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS · 2026 ·Vol. 114 ·期 8 ·e70141 · IF 3

Osteogenic GelMA/Calcium Oligophosphate Composite Hydrogel for Bone Regeneration

Yue Shu,Meizi Zhang,Bo Li,Ziyi Yan,Lingfei Liu,Yiran Wang,Congyan Xia,Zhongning Liu,Yanlin Chen

Critical-sized bone defects (CSDs) represent a major clinical challenge due to their limited self-healing capacity. Conventional hydrogels incorporating crystalline hydroxyapatite (HA) often fail to recapitulate the hierarchical nanostructure of native bone, leading to suboptimal regeneration outcomes. To overcome this, we developed a biomimetic hydrogel by molecularly integrating amorphous calcium phosphate oligomers (CPO) into gelatin methacryloyl (GelMA), enabling a bone-like organic–inorganic hybrid network. This composite exhibits outstanding performance: an ultimate strength of 192 kPa at 18 wt% CPO confirms robust mechanical reinforcement, while 54% mass retention after 56 days underscores exceptional degradation resistance and dose-dependent bioactivity, evidenced by a two-fold upregulation of alkaline phosphatase (ALP) activity. The amorphous CPO facilitates biomimetic HA nucleation within the GelMA matrix, mimicking the natural mineralization process. In a rat calvarial CSD model, the hydrogel promoted 60% bone volume regeneration within 12 weeks, significantly outperforming conventional composites, through seamless host integration, vascularized trabecular bone formation, and a collagen–mineral hierarchy resembling native osteogenesis. This study establishes CPO as a transformative component that converts passive scaffolds into bioactive osteogenic microenvironments, offering a clinically viable strategy for complex bone regeneration.

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