Biofabrication
·
2025
·Vol. 18
·期 1
·015010
·
IF 8
Xuan Jiao,Kexun Liu,Jie Wu,Peian Cai,Limeng Chao,Chang Liu,Kegong Chen,Xionghai Qin,Xin Tian,Yuanzhong Zhao,Hai Tian,Wei Chen
The transplantation of human bone marrow mesenchymal stem cells (hMSCs) exhibits promising therapeutic effects in the treatment of myocardial infarction (MI), however, its clinical application is limited due to the low survival rate of the transplanted cells. Three-dimensional (3D) bioprinted tissue engineering patches have demonstrated efficacy as a delivery approach to enhance the viability and engraftment of stem cells. In this study, we have developed a novel hMSCs tissue-engineered patch equipped with a nano-slow-release system using 3D bioprinting technology. The patch is based on a matrix material consisting of methacrylated gelatin (GelMA) and chitosan nanoparticles loaded with vascular endothelial growth factor (VEGF), which possesses pro-angiogenic effects. The resulting patch demonstrated excellent compatibility with hMSCs and enabled stable, sustained VEGF release. In vivo results showed that the patch significantly reduced cardiomyocyte apoptosis three days after MI, and improved cardiac function and myocardial fibrosis at 28 d post-surgery. These effects were closely associated with the patch’s potent angiogenic properties and favorable stem cell survival. In conclusion, this study successfully developed a 3D-printed tissue engineering patch with strong potential for clinical application, offering a promising new approach for the treatment of MI.
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Materials Today Bio
·
2025
·
IF 10.2
Xiaofei Zhang,Linzi Ma,Xiaotong Liu,Xingyu Zhou,Ao Wang,Yunhui Lai,Jun Zhang,Ying Li,Shiling Chen
Background Premature ovarian insufficiency (POI) refers to the severe decline or failure of ovarian function in women younger than 40 years of age. It is a serious hazard to women's physical and mental health, but current treatment options are limited. Mesenchymal stem cell-derived exosomes (MSC-Exo) exhibit promising potential as a therapeutic approach for POI. However, their clinical application is hindered by their instability and low long-term retention rate in vivo . Methods and Results In this study, miR-21 was identified as the predominant miRNA with low-expression in follicular fluid exosomes of POI patients and was shown to possess antiapoptotic activity. Next, we loaded miR-21 agomir to MSC-Exo to form Agomir21-Exo, which significantly reversed the apoptosis of granulosa cells in vitro. Moreover, we successfully developed GelMA hydrogel microspheres for encapsulating Agomir21-Exo through microfluidic technology, named GelMA-Ag21Exo, which had good injectability and significantly enhanced the stability and long-term retention of Agomir21-Exo in mice through sustained release. The release of Agomir21-Exo from GelMA-Ag21Exo notably alleviated the apoptosis of ovarian granulosa cells and improved the ovarian reserve and fertility in POI mice. Conclusion Our findings illustrate that activating miR-21 through Agomir21-Exo could improve the function of ovarian granulosa cells. The GelMA-Ag21Exo enhanced the exosome-based therapeutic efficacy of the Agomir21-Exo in vivo . These findings provide a novel and promising treatment strategy for POI patients.
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PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-29
·
IF 10.6
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
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BIOMATERIALS
·
2025
·
IF 12.9
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.
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高影响因子
Materials Today Bio
·
2022
·
IF 10.761
Zhengzhe Han,Lanlan Dong,Ang Li,Zongyue Li,Landie Fu,Zhichang Zhang,Xiang Li,Xiaolin Li
Wound healing and angiogenesis remain challenges for both clinical and experimental research worldwide. Periosteum-derived extracellular vesicles (P-sEVs) delivered by hydrogel dressings provide a potential strategy for wound defects to promote fast healing. In this study, we designed a NAGA/GelMA/Laponite/glycerol hydrogel wound dressing that can release P-sEVs to accelerate angiogenesis and wound healing (named [email protected] ) ( N -acryloyl glycinamide, NAGA). The wound dressing showed multiple functions, including efficient angiogenesis, tissue adhesion and a physical barrier. P-sEVs significantly enhanced the proliferation, migration, and tube formation of endothelial cells in vitro . The results of in vivo experiments showed that P-sE [email protected] accelerates the healing of a full-thickness defect wound model by stimulating the angiogenic process. The improved cell proliferation, tissue formation, remodeling, and re-epithelialization possibly resulted in the fast healing. This study shows that multifunctional hydrogel dressing combined with bioactive molecules can achieve fast and satisfactory wound healing in full-thickness wound defects and other related wounds.
研究领域:
组织工程
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再生医学
·
生物材料
·
细胞生物学
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高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
Zhihong Chen,Mingyu Jia,Yangyang Liu,Huajian Zhou,Xiaopan Wang,Min Wu
Background The use of autologous bone grafting is considered the most successful method for managing bone defects, particularly when utilizing cancellous bone grafts for the best outcomes. Nonetheless, the scarcity of cancellous bone presents a notable obstacle in remedying these defects. Consequently, it is essential to create reliable alternatives to cancellous bone grafts to ensure effective management of bone defects.Methods In this research, we created an injectable composite hydrogel stents using gelatin methacrylate (GelMA) hydrogel to mimic the collagen properties of cancellous bone, along with the inclusion of nanohydroxyapatite (nHA) to signify the inorganic element. Furthermore, we incorporated vascular endothelial growth factor (VEGF) to improve regenerative vascular capabilities. Before being implanted into rat cranium defect models, these composite hydrogel stents were co-cultured with human umbilical vein endothelial cells (HUVEC) and bone marrow mesenchymal stem cells (BMSC).Results The composite hydrogel stents exhibited a network structure with porosity, robust mechanical properties, and beneficial degradation traits. In the degradation phase, it steadily releases Ca²⁺ and VEGF, which encourages the proliferation, migration, and osteogenic differentiation of BMSCs from rats. Moreover, this release improves the ability of HUVECs to form tubes. Collectively, these mechanisms support the regeneration of blood vessels and bone in the cranium defect region of rats.Conclusion The composite hydrogel stents demonstrated excellent cytocompatibility and biological characteristics, as evidenced by its ability to enhance both osteogenesis and angiogenesis in vivo and in vitro. Consequently, it has the potential to act as an effective alternative to natural cancellous bone.
研究领域:
组织工程
·
再生医学
·
生物材料科学
·
骨科
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2022
·Vol. 20
·期 1
·1-17
·
IF 9.429
Wu Boda,Yang Jintao,Zu Yan,Chi Junjie,Shi Keqing
A film with elaborate microstructures that offers biomimetic properties and multi functionalities is highly desired in wound healing. Here, we develop an aligned hydrogel fiber film integrated with multi-active constituents to promote wound healing. Such fiber films are designed and constructed by photo-crosslinking the methacrylate gelatin (GelMA) doped with silver nanoparticles (Ag NPs) and iridium nanoparticles coated with polyvinylpyrrolidone (PVP-Ir NPs) in the precursor solution using electrospinning. The nature of GelMA hydrogel and the aligned arrangement of nanofibers endow the film with high-water content, self-degradability, improved bionic characteristics, oriented cell growth, and improved cell proliferation and migration. Moreover, the encapsulated nanozymes and Ag NPs offer the fiber film with superior reactive oxygen species (ROS) scavenging and antibacterial capability. The infected wound model shows that the multi-active hydrogel fiber film can reduce inflammation by killing bacteria and decomposing ROS, which accelerates the growth of new blood vessels and granulation tissue. Benefitting from these features, the versatile aligned GelMA fiber film demonstrates the clinically translational potential for wound healing.
研究领域:
材料科学
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生物医学工程
·
纳米技术
·
伤口愈合
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高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2024
·Vol. 113
·期 1
·e37844
·
IF 3.9
Qibin Han,Yinhua Qian,Lang Bai,Jing Zhou,Yuefeng Hao,Dan Hu,Zhouzhou Zhang,Xing Yang
Tendinopathy is a disorder characterized by pain and reduced function due to a series of changes in injured or diseased tendons. Inflammation and collagen degeneration are key contributors to the onset and chronic nature of tendinopathy. Acetyl-11-keto-β-boswellic acid (AKBA) is an effective anti-inflammatory agent widely used in chronic inflammatory disorders and holds potential for tendinopathy treatment; however, its therapeutic efficacy is limited by poor aqueous solubility. Here, we fabricated AKBA-encapsulated cationic liposome-gelatin methacrylamide (GelMA) microspheres (GM-Lipo-AKBA) using thin-film hydration and microfluidic technology for drug delivery therapy. GM-Lipo-AKBA exhibited high encapsulation efficiency, extended AKBA release for over 4 weeks, and prolonged degradation. In vitro and in vivo experiments demonstrated its effectiveness in improving inflammation and ECM remodeling in tendinopathy. In summary, the injectable nano-micron drug delivery platform provides a promising strategy for the sustained and localized delivery of AKBA for tendinopathy treatment.
研究领域:
药学
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生物医学工程
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骨科
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药物递送系统
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炎症研究
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-18
·
IF 10.2
Zhou Heng,Jing Shuili,Xiong Wei,Zhu Yangzhi,Duan Xingxiang,Li Ruohan,Peng Youjian,Kumeria Tushar,He Yan,Ye Qingsong
Spinal cord injury (SCI) is accompanied by loss of Zn2+, which is an important cause of glutamate excitotoxicity and death of local neurons as well as transplanted stem cells. Dental pulp stem cells (DPSCs) have the potential for neural differentiation and play an immunomodulatory role in the microenvironment, making them an ideal cell source for the repair of central nerve injury, including SCI. The zeolitic imidazolate framework 8 (ZIF-8) is usually used as a drug and gene delivery carrier, which can release Zn2+ sustainedly in acidic environment. However, the roles of ZIF-8 on neural differentiation of DPSCs and the effect of combined treatment on SCI have not been explored. ZIF-8-introduced DPSCs were loaded into gelatin methacryloyl (GelMA) hydrogel and in situ injected into the injured site of SCI rats. Under the effect of ZIF-8, axon number and axon length of DPSCs-differentiated neuro-like cells were significantly increased. In addition, ZIF-8 protected transplanted DPSCs from apoptosis in the damaged microenvironment. ZIF-8 promotes neural differentiation and angiogenesis of DPSCs by activating the Mitogen-activated protein kinase (MAPK) signaling pathway, which is a promising transport nanomaterial for nerve repair.
研究领域:
神经科学
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干细胞生物学
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材料科学
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再生医学
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高影响因子
JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE
·
2022
·Vol. 33
·期 8
·1-14
·
IF 4.727
Xu Hongjie,Wang Jingjing,Wu Di,Qin Dajiang
Background Diabetic wound is a severe complication of diabetes. Stem cell is considered as a promising therapy for diabetic skin wounds. Hydrogel can supply niche for cells adhesion and survival to improve the efficacy of stem cell therapy, but the development of hydrogel with suitable properties remains a great challenge. Thus, our study was conducted to combine an optimized hydrogel with stem cell to improve complex diabetic wound treatment. Methods This study constructed a hydrogel with low toxicity and adjustable mechanical properties from gelatin methacrylate (GelMA) and chitosan-catechol (Chi-C), and encapsulated human umbilical cord-mesenchymal stem cells (hUMSCs) to repair full-thickness diabetic wound. Results We explored the relationship between mechanical stiffness and cell proliferation and differentiation potency, and found 10% GelMA hydrogel with an optimal stiffness improved hUMSCs adhesion, proliferation, and differentiation potency maintenance in vitro. Assistant with optimized hydrogel encapsulating hUMSCs, diabetic wound healing process was greatly accelerated, including accelerated wound closure, inhibited secretion of inflammatory factors TNF-α and IL-1β, promoted vascular regeneration and collagen deposition after treatment of hUMSCs. Conclusions The optimized hydrogel encapsulating hUMSCs improved diabetic wound healing, and has a broad implication for the treatment of diabetic complication.
Diabetic wound is a severe complication of diabetes. Stem cell is considered as a promising therapy for diabetic skin wounds. Hydrogel can supply niche for cells adhesion and survival to improve the efficacy of stem cell therapy. This study constructed a hydrogel with low toxicity and adjustable mechanical properties from gelatin methacrylate (GelMA) and chitosan-catechol (Chi-C), and encapsulated human umbilical cord-mesenchymal stem cells (hUMSCs) to repair full-thickness diabetic wound. Hydrogel of 10% GelMA with an optimal stiffness improved hUMSCs adhesion, proliferation, and differentiation potency maintenance in vitro. Assistant with optimized hydrogel encapsulating hUMSCs, diabetic wound healing process was greatly accelerated, including accelerated wound closure, inhibited secretion of inflammatory factors TNF-α and IL-1β, promoted vascular regeneration and collagen deposition after treatment of hUMSCs. The study supplies an alternative treatment for diabetic complication. Hydrogel-hUMSCs combined treatment accelerates wound closure in diabetic mice. A . Representative images of wounds during 21-day in vivo experiments. B . Quantification of wound closure rate (%) over 21-day period. C . HE staining of wounds at days 7, 14 and 21. The bar corresponds to 200 μm.
研究领域:
生物医学工程
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组织工程
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干细胞研究
·
伤口愈合
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PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Yujian Hui,Jiannan Mao,Min Rui,Yiyang Huang,Xinzhao Jiang,Yichang Xu,Wei Wang,Jie Wu,Liang Zhou,Kun Xi,Lixin Huang,Liang Chen
The healing of bone defects among diabetic patients presents a critical challenge due to the pathological microenvironment, characterized by hyperglycemia, excessive reactive oxygen species (ROS) production, and inflammation. Herein, multifunctional composite microspheres, termed GMAP are developed, using a microfluidic technique by incorporating Au@Pt nanoparticles (NPs) and GelMA hydrogel to modulate the diabetic microenvironment for promoting bone regeneration. The GMAP enables the sustained release of Au@Pt NPs, which function as bimetallic nanozymes with dual enzyme-like activities involving glucose oxidase and catalase. The synergistic effect allows for efficient glucose consumption and ROS elimination concurrently. Thus, the GMAP effectively protects the proliferation of bone marrow mesenchymal stem cells (BMSCs) under adverse high-glucose conditions. Furthermore, it also promotes the osteogenic differentiation and paracrine capabilities of BMSCs, and subsequently inhibits inflammation and enhances angiogenesis. In vivo diabetic rats bone defect model, it is demonstrated that GMAP microspheres significantly improve bone regeneration, as verified by micro-computed tomography and histological examinations. This study provides a novel strategy for bone regeneration by modulating the diabetic microenvironment, presenting a promising approach for addressing the complex challenges associated with bone healing in diabetic patients.
研究领域:
材料科学
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生物医学工程
·
再生医学
·
纳米技术
·
糖尿病研究
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-18
·
IF 10.6
Xu Chao,Yang Kun,Xu Yin,Meng Xiangfu,Zhou Ying,Xu Yanping,Li Xueyao,Qiao Weihua,Shi Jiawei,Zhang Donghui,Wang Jianglin,Xu Weilin,Yang Hongjun,Luo Zhiqiang,Dong Nianguo
Tissue engineered heart valves (TEHVs) demonstrates the potential for tissue growth and remodel, offering particular benefit for pediatric patients. A significant challenge in designing functional TEHV lies in replicating the anisotropic mechanical properties of native valve leaflets. To establish a biomimetic TEHV model, we employed melt-electrowriting (MEW) technology to fabricate an anisotropic PCL scaffold. By integrating the anisotropic MEW-PCL scaffold with bioactive hydrogels (GelMA/ChsMA), we successfully crafted an elastic scaffold with tunable mechanical properties closely mirroring the structure and mechanical characteristics of natural heart valves. This scaffold not only supports the growth of valvular interstitial cells (VICs) within a 3D culture but also fosters the remodeling of extracellular matrix of VICs. The in vitro experiments demonstrated that the introduction of ChsMA improved the hemocompatibility and endothelialization of TEHV scaffold. The in vivo experiments revealed that, compared to their non-hydrogel counterparts, the PCL-GelMA/ChsMA scaffold, when implanted into SD rats, significantly suppressed immune reactions and calcification. In comparison with the PCL scaffold, the PCL-GelMA/ChsMA scaffold exhibited higher bioactivity and superior biocompatibility. The amalgamation of MEW technology and biomimetic design approaches provides a new paradigm for manufacturing scaffolds with highly controllable microstructures, biocompatibility, and anisotropic mechanical properties required for the fabrication of TEHVs.
研究领域:
组织工程
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生物材料
·
心血管工程
·
生物医学工程
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