INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Zhixiang Mu,Yan Yang,Guanyao Zhang,Xiaobin Yang,Qingqing Dong,Jiaying Ma,Anlin Li,Ke Li,Jiajun Hu,Xuanxin Yang,Qiuqiu Mu,Xiaojie Wang
Diabetic wound healing remains challenging due to persistent hyperglycemia-driven reactive oxygen species (ROS) accumulation and mitochondrial dysfunction. To address this, we engineered a photocurable hydrogel ( [email protected] ) composed of gelatin methacryloyl (GelMA) and bovine serum albumin methacryloyl (BSAMA) to encapsulate aucubin (Auc). Systematic evaluation of GelMA/BSAMA ratios identified the 1:1 formulation as optimal, exhibiting superior mechanical strength. The binding ability of BSAMA to Auc could realize sustained release. Furthermore, GelMA's MMP-9-responsive domains enabled accelerated Auc release in inflammatory microenvironments. The design integrates BSAMA's drug-binding capacity with GelMA's MMP-9 responsiveness to achieve spatiotemporal drug release. In vitro studies demonstrated that the hydrogel effectively scavenges ROS and restores mitochondrial membrane potential, thereby disrupting the ROS storm cycle. This antioxidative effect further suppressed the production of pro-inflammatory cytokines (IL-1β, IL-6) and the overexpression of MMP-9. In a type 2 diabetic rat model, the hydrogel accelerated full-thickness wound closure, with histological analysis revealing dense collagen deposition and enhanced angiogenesis. By synergistically integrating GelMA's MMP-9-triggered drug release with BSAMA's Auc-binding capacity, the hydrogel establishes a multifunctional platform that couples microenvironment-responsive drug delivery with anti-oxidative, anti-inflammatory, and pro-angiogenic functions, offering a promising solution for diabetic wound management.
研究领域:
生物材料
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药剂学
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伤口愈合
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糖尿病研究
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生物工程
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纳米医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2025
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IF 4.9
Sijia Tian,Haoying Li,Yanxin Niu,Xueyan Hu,Yongxue Guo
Transcatheter arterial chemoembolization (TACE) is an important method in the treatment of liver cancer and identification of an ideal microsphere for embolization is a key step in its development. Here, we used a microfluidic device to prepare uniformly sized Photopolymerized pH-Responsive GelMA Microspheres with Doxorubicin Modification (DOX-GelMA) that integrated embolization and drug delivery properties. The acid-sensitive doxorubicin (DOX) prodrug was synthesized through a three-step reaction and coupled during curing of the microspheres under UV irradiation. The microspheres exhibited significant pH-responsive drug release in the tumor microenvironment and had a good degradation performance over 18 days. Microscopic images and scanning electron microscopy results showed that the microspheres had good sphericity and uniform particle size (96.61 ± 0.046 μm), and that the particle size and their degree of swelling were suitable for embolization therapy. In vitro cytotoxicity and blood compatibility experiments showed that the microspheres were good biocompatible. The drug-loaded microspheres had obvious inhibitory effect on HepG2. A rabbit ear embolization study demonstrated that the microspheres could effectively block arterial blood flow. The DOX-GelMA microspheres simultaneously achieved physical targeted therapy and chemotherapy, and had great prospects in TACE therapy.
研究领域:
生物医学工程
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药学
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肿瘤学
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材料科学
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医疗器械
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
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IF 15.1
Zhenming Yang,Shuangshuang Fan,Wei Ma,Zhiguang Li,Xuehong Ren
Complex bacterial infection and inevitable movement are the two most concerning issues in joint wound healing. In this work, N -halamine structure was introduced into polydopamine nanoparticles (PDNPs) and encapsulated in a gelatin methacryloyl (GelMA)/silk fibroin (SF) matrix to endow the patches with efficient and broad-spectrum antibacterial activity. Zone of inhibition and in vivo antibacterial tests confirm that the addition of N -halamine containing organic nanoparticles as antibacterial components is a convenient and feasible strategy in the development of wound healing antibacterial materials. Here, dopamine methacrylamide (DMA) was synthesized and grafted onto the gelatin methacryloyl in patches with UV irradiation to get a reasonable adhesion. The liver prick injury model showed that the flexible adhesive GelMA/SF-based patch could be fixed on the wound area with rapid hemostatic effect. Furthermore, the resultant patches possess good flexibility, breathability and excellent biocompatibility. The histology analysis indicated the designed patches demonstrated less inflammatory response, significantly enhanced vascularization and the regeneration of dermis and epidermis. In summary, these N -halamine hemostatic GelMA/SF patches hold a promise for diverse practical acute trauma treatments.
研究领域:
生物材料学
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医学工程
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组织工程
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
·
IF 7.7
Feng Cheng,Lei Xu,Xiao Zhang,Jinmei He,Yudong Huang,Hongbin Li
Recently, photothermal nanomaterials has attracted enormous interests owing to their enhanced therapeutic effects and less adverse effects in the treatment of infectious diseases. Herein, this work presents a photothermally responsive antimicrobial, bioadhesive hydrogel through three dimensions (3D) printing technology for treatment the wound infection. The hydrogel is based on a visible-light-activated naturally derived polymer (GelMA), GelMA grafted with dopamine (GelMA-DA) and the polydopamine coated reduced graphene oxide (rGO@PDA), which can provide the multifunctional such as photothermal antibacterial, antioxidant, conductivity, adhesion and hemostasis performance to accelerate wound healing . The developed hydrogel shown the excellent adhesion capability to adhere the in vitro physiological tissues and glass surface. Moreover, the fabricated hydrogel also exhibited excellent cytocompatibility to L929 cells which is a vital biofunction for efficiently promoting cell proliferation and migration in vitro. The hydrogel also showed remarkable photothermally responsive antimicrobial capability against two strains (99.3 % antibacterial ratio for E. coli and 98.6 % antibacterial ratio for S. aureus ). Furthermore, it could support the wound repair and regeneration of S. aureus infected full-thickness wound defects in rats. Overall, the 3D printed hydrogel could be used as a photothermal platform for the development of more effective therapies against the infected wound.
研究领域:
生物医学工程
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材料科学
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感染性疾病治疗
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产品关联
DOI
PubMed
高影响因子
Biomedical Materials
·
2025
·
IF 3.7
Naiwen Zhang,Cong Ma,Fei Shao,Huanan Wang,Xiang Ma
Retinal degenerative diseases, including age-related macular degeneration (AMD) and retinitis pigmentosa (RP), are leading causes of blindness globally, characterized by progressive degeneration of retinal pigment epithelium (RPE) and photoreceptor (PR) cells. Despite advancements, current therapies have not substantially arrested disease progression. Cell replacement therapy using healthy RPE and PR cells holds promise but faces obstacles such as poor cell survival, inadequate integration, and transplantation difficulties. To address these issues, tissue engineering combined with 3D printing has become a focal point. This study investigates the use of four hydrogels—GelMA, HAMA, AlgMA, and PEGDA—and their various crosslinked combinations for creating hydrogel thin-layer matrices conducive to RPE cell growth. PEGDA/GelMA hydrogel demonstrated optimal support for cell spreading and proliferation, which is not achievable with hydrogels matrices of other formulations. The relationship between the mechanical properties of PEGDA/GelMA hydrogels and cell growth was further refined. PEGDA600-20 hydrogel with a compressive modulus of 1245.07 ± 20.79 kPa was selected based on time-course viability assays, leading to the development of the optimized Fib@PEGDA/GelMA hydrogel exhibited exceptional biocompatibility. Compared to PEGDA/GelMA, CCK-8 assays demonstrated significantly improved relative cell viability at 24 h, 48 h, and 72 h, with increases of 17.73 ± 1.22%, 14.54 ± 3.63%, and 19.04 ± 2.31%, respectively on Fib@PEGDA/GelMA matrix. qRT-PCR results indicated a mitigation of epithelial-mesenchymal transition (EMT), as evidenced by downregulation of EMT markers (CDH2, COL1A1, and FN1), accompanied by reduced IL-6 levels. Fib@PEGDA/GelMA hydrogel enhanced phagocytic activity in ARPE-19 cells and promoted functional expression in hiPSC-RPEs. Additionally, the hydrogel showed favorable in vivo biocompatibility following subcutaneous implantation of RCS rats at 1, 2, and 4 weeks post-implantation evidenced by HE and Masson's staining. This system offers a promising bioink for 3D-printed retinal cell scaffolds and paves the way for future advancements in cell replacement therapies for retinal degenerative diseases.
研究领域:
组织工程学
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再生医学
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眼科
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产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2024
·
IF 5.5
Ping Song,Xingyu Gui,Lina Wu,Xinyu Su,Wenzheng Zhou,Zeyu Luo,Boqing Zhang,Pin Feng,Wei Wei,Chen Fan,Yunhong Wu,Weinan Zeng,Changchun Zhou,Yujiang Fan,Zongke Zhou
Severe bone defects resulting from trauma and diseases remain a persistent clinical challenge. In this study, a hierarchical biomimetic microporous hydrogel composite scaffold was constructed by mimicking the hierarchical structure of bone. Initially, gelatin methacrylamide (GelMA) and methacrylic anhydride silk fibroin (SilMA) were synthesized, and GelMA/SilMA inks with suitable rheological and mechanical properties were prepared. Biomimetic micropores were then generated by using an aqueous two-phase emulsification method. Subsequently, biomimetic microporous GelMA/SilMA was mixed with hydroxyapatite (HAp) to prepare biomimetic microporous GelMA/SilMA/HAp ink. Hierarchical biomimetic microporous GelMA/SilMA/HAp (M-GSH) scaffolds were then fabricated through digital light processing (DLP) 3D printing. Finally, in vitro experiments were conducted to investigate cell adhesion, proliferation, and inward migration as well as osteogenic differentiation and vascular regeneration effects. In vivo experiments indicated that the biomimetic microporous scaffold significantly promoted tissue integration and bone regeneration after 12 weeks of implantation, achieving 42.39% bone volume fraction regeneration. In summary, this hierarchical biomimetic microporous scaffold provides a promising strategy for the repair and treatment of bone defects.
研究领域:
生物医学工程
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组织工程
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再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
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2025
·
IF 4.8
Dandan Zhou,Xiaoxiao Li,Wencun Liu,Mingjun Zhang,Ying Cheng,Zhousong Xu,Jian Gao,Yiyang Wang
Liver cancer, a highly aggressive malignancy, continues to present significant challenges in therapeutic management due to its pronounced chemoresistance. This resistance, which undermines the efficacy of conventional chemotherapy and targeted therapies, is driven by multifaceted mechanisms, with increasing emphasis placed on the protective role of the tumor microenvironment (TME). The hepatocellular carcinoma extracellular matrix (ECM), a primary non-cellular component of the TME, has emerged as a critical regulator in cancer progression and drug resistance, particularly in hepatocellular carcinoma cell (HCC). In this study, a hybrid biomimetic hydrogel was engineered by integrating decellularized hepatocellular carcinoma matrix (DHCM) with gelatin methacrylate (GelMA) precursors. This composite DHCM/GelMA hydrogel was designed to replicate the physicochemical and functional properties of the hepatocellular carcinoma ECM, thereby offering a biomimetic platform to explore the interactions between HCCs and their microenvironment. Leveraging a custom-designed microfluidic 3D printing platform, we achieved high-throughput fabrication of HCC-encapsulated DHCM/GelMA microgels, characterized by enhanced uniformity, biocompatibility, and scalability. These microgels facilitated the construction of hepatocellular carcinoma microtissues, which were subsequently employed for chemoresistance studies. Our findings revealed that DHCM/GelMA microgels closely mimic the hepatocellular carcinoma tumor microenvironment, effectively recapitulating key features of ECM-mediated drug resistance. Mechanistic studies further demonstrated that DHCM significantly upregulates the expression of Aquaporin 3 (AQP3) in the encapsulated HCCs. This upregulation potentially activates mTOR signaling-associated autophagy pathways, thereby enhancing chemoresistance in HCCs. These biomimetic models provide a robust and versatile platform for studying the underlying mechanisms of drug resistance and evaluating therapeutic interventions. This innovative approach highlights the potential of DHCM/GelMA microgels as a transformative tool in cancer-associated tissue engineering and anticancer drug screening. By enabling detailed investigations into the role of ECM in chemoresistance, this study contributes to advancing therapeutic research and offers promising strategies to overcome drug resistance, ultimately improving clinical outcomes in liver cancer treatment.
研究领域:
生物医学工程
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肿瘤学
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药理学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN POLYMER JOURNAL
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2024
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IF 5.8
Sheng Ding,Shaoqin He,Lian Shen,Qingliang Yang,Gensheng Yang
Gelatin methacryloyl (GelMA) hydrogels have become a key biomaterial in various biomedical fields, such as tissue regeneration engineering and drug delivery, due to their exceptional biocompatibility and customizable physical and chemical characteristics. The resemblance of GelMA to the extracellular matrix and its ability to be cured with light make it a popular choice for researchers. This research delves into how the material properties of GelMA hydrogels, specifically the density of the molecular network (DMN), impact their performance in different applications. By preparing GelMA hydrogels with different degrees of substitution (DS) and concentrations, and utilizing these attributes as key measurable parameters for determining DMN, we conducted a comprehensive evaluation of properties relevant to biological applications. We also suggest strategies for optimizing these properties. Through the application of the DMN theory, we show that precise control over material properties allows for tailored customization of GelMA hydrogels for specific tissue engineering and drug delivery purposes. This study offers valuable insights into the optimization of GelMA hydrogel properties to advance the field of tissue engineering and improve customization of cellular microenvironments.
研究领域:
生物医学工程
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组织工程
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药物递送系统
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
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2023
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IF 8
Suyang Zheng,Dong Li,Qingbai Liu,Cheng Tang,Wenhao Hu,Shengshan Ma,Yan Xu,Yong Ma,Yang Guo,Bo Wei,Chuanlin Du,Liming Wang
Purpose This study aims to investigate the impact of enhancing subchondral bone repair on the efficacy of articular cartilage restoration, thereby achieving improved osteochondral regeneration outcomes.Methods In this study, we modified the surface of nano-hydroxyapatite (n-HAp) through alkylation reactions to prepare n-HApMA. Characterization techniques, including X-ray diffraction, infrared spectroscopy scanning, thermogravimetric analysis, particle size analysis, and electron microscopy, were employed to analyze n-HApMA. Bioinks were prepared using n-HApMA, high porosity GelMA hydrogel, and adipose tissue derived stromal cells (ADSCs). The rheological properties of the bioinks during photocuring were investigated using a rheometer. Based on these bioinks, a biphasic scaffold was constructed. The viability of cells within the scaffold was observed using live-dead cell staining, while the internal morphology was examined using scanning electron microscopy. The stiffness of the scaffold was evaluated through compression testing. Scaffolds were implanted into the osteochondral defects of New Zealand rabbit knees, and microCT was utilized to observe the subchondral bone repair. Hematoxylin and eosin (H&E) staining, Masson’s trichrome staining, and Safranin O/Fast Green staining were performed to assess the regeneration of subchondral bone and cartilage. Furthermore, immunohistochemical staining was employed to detect the expression of osteogenic and chondrogenic-related molecules.Results Scaffold characterization revealed that surface modification enables the uniform distribution of n-HApMA within the GelMA matrix. The incorporation of 5% n-HApMA notably enhanced the elastic modulus and stiffness of the 6% high-porosity GelMA in comparison to n-HAp. Moreover, in-vivo study showed that the homogeneous dispersion of n-HApMA on the GelMA matrix facilitated the osteogenic differentiation of adipose-derived stem cells (ADSCs) and promoted osteochondral tissue regeneration.Conclusion These findings suggest potential applications of the n-HApMA/GelMA composite in the field of tissue engineering and regenerative medicine.
研究领域:
生物材料学
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组织工程
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再生医学
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产品关联
DOI
PubMed
高影响因子
Bio-Design and Manufacturing
·
2023
·Vol. 6
·期 4
·464-477
·
IF 7.9
Qiao Qian,Zhang Xiang,Yan Zhenhao,Hou Chuanyu,Zhang Juanli,He Yong,Zhao Na,Yan Shujie,Gong Youping,Li Qian
Cryobioprinting has tremendous potential to solve problems to do with lack of shelf availability in traditional bioprinting by combining extrusion bioprinting and cryopreservation. In order to ensure the viability of cells in the frozen state and avoid the possible toxicity of dimethyl sulfoxide (DMSO), DMSO-free bioink design is critical for achieving successful cryobioprinting. A nontoxic gelatin methacryloyl-based bioink used in cryobioprinting is composed of cryoprotective agents (CPAs) and a buffer solution. The selection and ratio of CPAs in the bioink directly affect the survival of cells in the frozen state. However, the development of universal and efficient cryoprotective bioinks requires extensive experimentation. We first compared two commonly used CPA formulations via experiments in this study. Results show that the effect of using ethylene glycol as the permeable CPA was 6.07% better than that of glycerol. Two datasets were obtained and four machine-learning models were established to predict experimental outcomes. The predictive powers of multiple linear regression (MLR), decision tree (DT), random forest (RF), and artificial neural network (ANN) approaches were compared, suggesting an order of ANN>RF>DT>MLR. The final selected ANN model was then applied to another dataset. Results reveal that this machine-learning method can accurately predict the effects of cryoprotective bioinks composed of different CPAs. Outcomes also suggest that the formulations presented here have universality. Our findings are likely to greatly accelerate research and development on the use of bioinks for cryobioprinting. Graphic abstract
研究领域:
生物工程
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细胞生物学
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产品关联
DOI
高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Liu Xin,Li Jiale,Liu Shuyu,Long Yan,Kang Ching,Zhao Chen,Wei Ling,Huang Shaoqi,Luo Yi,Dai Bo,Zhu Xiangjia
Posterior capsule opacification (PCO) remains the predominant complication following cataract surgery, significantly impairing visual function restoration. In this study, we developed a PCO model that closely mimics the anatomical structure of the crystalline lens capsule post-surgery. The model incorporated a threaded structure for accurate positioning and observation, allowing for opening and closing. Utilizing 3D printing technology, a stable external support system was created using resin material consisting of a rigid, hollow base and cover. To replicate the lens capsule structure, a thin hydrogel coating was applied to the resin scaffold. The biocompatibility and impact on cellular functionality of various hydrogel compositions were assessed through an array of staining techniques, including calcein-AM/PI staining, rhodamine staining, BODIPY-C11 staining, and EdU staining in conjunction with transwell assays. Additionally, the PCO model was utilized to investigate the effects of eight drugs with anti-inflammatory and anti-proliferative properties, including 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), THZ1, sorbinil, 4-octyl itaconate (4-OI), xathohumol, zebularine, rapamycin, and caffeic acid phenethyl ester (CAPE), on human lens epithelial cells (HLECs). Confocal microscopy facilitated comprehensive imaging of the PCO model. The results demonstrated that the GelMA 60 5% + PLMA 2% composite hydrogel exhibited superior biocompatibility and minimal lipid peroxidation levels among the tested hydrogels. Moreover, compared to using hydrogel as the material for 3D printing the entire model, applying surface hydrogel spin coating with parameters of 2000 rpm x 2 on the resin-based 3D printed base yielded a more uniform cell distribution and reduced apoptosis. Furthermore, rapamycin, 4-OI, and AICAR demonstrated potent antiproliferative effects in the drug intervention study. Confocal microscopy imaging revealed a uniform distribution of HLECs along the anatomical structure of the crystalline lens capsule within the PCO model, showcasing robust cell viability and regular morphology. In conclusion, the PCO model provides a valuable experimental platform for studying PCO pathogenesis and exploring potential therapeutic interventions.
研究领域:
眼科学
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生物材料学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2022
·Vol. 18
·期 25
·2106357
·
IF 15.153
Sili Yi,Qiong Liu,Zeyu Luo,Jacqueline Jialu He,Hui-Lin Ma,Wanlu Li,Di Wang,Cuiping Zhou,Carlos Ezio Garciamendez,Linxi Hou,Jin Zhang,Yu Shrike Zhang
It is well-known that tissue engineering scaffolds that feature highly interconnected and size-adjustable micropores are oftentimes desired to promote cellular viability, motility, and functions. Unfortunately, the ability of precise control over the microporous structures within bioinks in a cytocompatible manner for applications in 3D bioprinting is generally lacking, until a method of micropore-forming bioink based on gelatin methacryloyl (GelMA) was reported recently. This bioink took advantage of the unique aqueous two-phase emulsion (ATPE) system, where poly(ethylene oxide) (PEO) droplets are utilized as the porogen. Considering the limitations associated with this very initial demonstration, this article has furthered the understanding of the micropore-forming GelMA bioinks by conducting a systematic investigation into the additional GelMA types (porcine and fish, different methacryloyl-modification degrees) and porogen types (PEO, poly(vinyl alcohol), and dextran), as well as the effects of the porogen concentrations and molecular weights on the properties of the GelMA-based ATPE bioink system. This article exemplifies not only the significantly wider range of micropore sizes achievable and better emulsion stability, but also the improved suitability for both extrusion and digital light processing bioprinting with favorable cellular responses.
研究领域:
生物材料
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组织工程
·
生物打印
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）