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Biomedical Materials · 2024 · IF 3.9

Carboxymethyl chitosan-methacrylic acid gelatin hydrogel for wound healing and vascular regeneration

Jingrong Yu,Zhengkun Gao,Qingyue Han,Zi Wang,Wenjie Zhang,Jie Zhao,Shan Qiao,Xinxin Zou,Fengjie Huang

At present, wound dressings in clinical applications are primarily used for superficial skin wounds.However these dressings have significant limitations, including poor biocompatibility and limited ability to promote wound healing. To address this issue, t this study used aldehyde polyethylene glycol as the cross-linking agent to design a carboxymethyl chitosan-methacrylic acid gelatin hydrogel with enhanced biocompatibility, which can promote wound healing and angiogenesis.The CSDG hydrogel exhibites acid sensitivity, with a swelling ratio of up to 300%. Additionally, it exhibited excellent resistance to external stress, withstanding pressures of up to 160 kPa and self-deformation of 80%. Compared to commercially available chitosan wound gels, the CSDG hydrogel demonstrates excellent biocompatibility, antibacterial properties, and hemostatic ability. Both in vitro and in vivo results showed that the CSDG hydrogel accelerated blood vessel regeneration by upregulating the expression of CD31, IL-6, FGF, and VEGF, thereby promoting rapid healing of wounds. In conclusion, this study successfully prepared the CSDG hydrogel wound dressings, providing a new approach and method for the development of hydrogel dressings based on natural macromolecules.

CAS / MDL: 538-75-0 1122-58-3
研究领域: 生物医学工程 · 材料科学 · 伤口愈合 · 组织工程
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SCIENCE OF THE TOTAL ENVIRONMENT · 2020 · IF 6.551

Toxicity of silver nanoparticles on wound healing: A case study of zebrafish fin regeneration model

Shaochen Pang,Yue Gao,Fengbang Wang,Yuanyuan Wang,Mengxi Cao,Wenjuan Zhang,Yong Liang,Maoyong Song,Guibin Jiang

Dressings coated with silver nanoparticle (AgNP) are widely used in the management of acute and chronic wounds. However, whether AgNP exerts toxicity on wound healing remains ambiguous. To demonstrate the effects of AgNP on wound healing, we precisely quantified the recovery speed of wound by taking advantage of the fin regeneration of zebrafish. This method also enabled assessment of the adverse effect of AgNP on various steps of wound healing in vivo . We revealed that AgNP treatment at the concentration of 2 μg/ml impaired fin regeneration when exposure was performed at the phases of epithelialization and the beginning of blastema formation. Cell proliferation of regenerative blastema was significantly decreased after AgNP exposure. But the canonical signals including Wingless/Integrated (Wnt), Notch and Fibroblast growth factor (Fgf) which play important roles in cell proliferation during fin regeneration were not modulated at 36 hours post amputation (hpa). Further study showed that AgNP impaired fin regeneration through declining amputation-induced ROS as early as epithelialized phase at 18 hpa, rather than inducing ROS generation. AgNP exposure also promoted recruitment of neutrophils in the early phase of wound healing, which suggests that this event dampened amputation-induced ROS. Overall, this study suggested that application of AgNP-coated dressings should be carefully considered at the beginning stage of wound healing.

研究领域: 纳米技术 · 伤口愈合 · 斑马鱼生物学 · 再生医学
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Journal of Materials Chemistry B · 2024 · IF 6.1

Development and evaluation of 3D composite scaffolds with piezoelectricity and biofactor synergy for enhanced articular cartilage regeneration

Bowen Xie,Hebin Ma,Fengyuan Yang,Hongguang Chen,Ya’nan Guo,Hongxing Zhang,Tengfei Li,Xiaogang Huang,Yantao Zhao,Xiaojie Li,Junjie Du

The inability of articular cartilage to self-repair following injuries frequently precipitates osteoarthritis, profoundly affecting patients' quality of life. Given the limitations inherent in current clinical interventions, an urgent need exists for more effective cartilage regeneration methodologies. Previous studies have underscored the potential of electrical stimulation in cartilage repair, thus motivating the investigation of innovative strategies. The present study introduces a three-dimensional scaffold fabricated through a composite technique that leverages the synergy between piezoelectricity and biofactors to enhance cartilage repair. This scaffold is composed of polylactic acid (PLLA) and barium titanate (BT) for piezoelectric stimulation and at the bottom with a collagen-coated layer infused with fibroblast growth factor-18 (FGF-18) for biofactor delivery. Designed to emulate the properties of natural cartilage, the scaffold enables controlled generation of piezoelectric charges and the sustained release of biofactors. In vitro tests confirm that the scaffold promotes chondrocyte proliferation, matrix hyperplasia, cellular migration, and the expression of genes associated with cartilage formation. Moreover, in vivo studies on rabbits have illustrated its efficacy in catalyzing the in situ regeneration of articular cartilage defects and remodeling the extracellular matrix. This innovative approach offers significant potential for enhancing cartilage repair and holds profound implications for regenerative medicine.

研究领域: 组织工程 · 再生医学 · 生物医用材料 · 骨科
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Biomaterials Science · 2017 ·Vol. 5 ·期 11 ·2251-2267 · IF 4.21

Hydration of hydrogels regulates vascularization in vivo

Jie Wu,Kunxi Zhang,Xi Yu,Jianxun Ding,Lei Cui,Jingbo Yin

The key barrier to the clinical application of tissue engineering scaffolds is the limitation of rapid and sufficient vascularization. Adipose-derived stem cells (ASCs), especially multicellular aggregates, exhibited a promising angiogenic activity. Herein, we designed a series of poly(L-glutamic acid) (PLGA)-based hydrogels with tunable hydration to control the in situ formation of multicellular spheroids. Oligo(ethylene glycol)s (OEGs) were employed to regulate the hydration of hydrogels. The hydrogel cross-linked with ethylene glycol (OEG1) supported the most excellent adhesion and proliferation of human ASCs in vitro. However, as the hydration of hydrogels strengthened, the adherent ASCs were gradually replaced with multicellular spheroids. Moreover, the in situ formation of spheroids was more effective in upregulating hypoxia-adaptive signals (e.g., hypoxia-inducible factor-1α, HIF-1α) and enhancing the secretion of angiogenic factors (e.g., vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2)) compared to adherent cells in OEG1 hydrogels. The hydrogel cross-linked with oligo(ethylene glycol)400 (OEG9) carrying spheroids induced a high angiogenic response of host tissue in vivo, resulting in an improved system vascularization, compared to adherent cells in the OEG1 hydrogel. These features indicated that the PLGA-based hydrogels were expected to be applied toward bone and fat tissue regeneration.

研究领域: 组织工程 · 生物材料 · 再生医学 · 细胞生物学 · 血管生成
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ACS Applied Materials & Interfaces · 2024 · IF 8.3

Wearable Magnetoelectric Stimulation for Chronic Wound Healing by Electrospun CoFe2O4@CTAB/PVDF Dressings

Qi Ke,Xinyi Zhang,Yuan Yang,Qi Chen,Jianyu Su,Youhong Tang,Liming Fang

Magnetoelectric stimulation is a promising therapy for various disorders due to its high efficacy and safety. To explore its potential in chronic skin wound treatment, we developed a magnetoelectric dressing, CFO@CTAB/PVDF (CCP), by electrospinning cetyltrimethylammonium bromide-modified CoFe2O4 (CFO) particles with polyvinylidene fluoride. Cetyltrimethylammonium bromide (CTAB) serves as a dispersion surfactant for CFO, with its quaternary ammonium cations imparting antibacterial and hydrophilic properties to the dressing. Electrospinning polarizes polyvinylidene fluoride (PVDF) molecules and forms a fibrous membrane with flexibility and breathability. With a wearable electromagnetic induction device, a dynamic magnetic field is established to induce magnetostrictive deformation of CFO nanoparticles. Consequently, a piezoelectric potential is generated on the surface of PVDF nanofibers to enhance the endogenous electrical field in the wound, achieving a cascade coupling of electric–magnetic–mechanical–electric effects. Bacteria and cell cultures show that 2% CTAB effectively balances antibacterial property and fibroblast activity. Under dynamic magnetoelectric stimulation, the CCP dressing demonstrates significant upregulation of TGF-β, FGF, and VEGF, promoting L929 cell adhesion and proliferation. Moreover, it facilitates the healing of diabetic rat skin wounds infected with Staphylococcus aureus within 2 weeks. Histological and molecular biology evaluations confirm the anti-inflammatory effect of CTAB and the accelerated formation of collagen and vessel by electrical stimulation. This work provides insights into the application of magnetoelectric stimulation in the healing of chronic wounds.

研究领域: 生物医学工程 · 材料科学 · 伤口愈合 · 生物材料 · 纳米技术 · 组织工程
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Bioactive Materials · 2025 · IF 20.3

Bioinspired scaffold recapitulating chondrogenic ontogeny and microenvironment for functional cartilage regeneration

Tianyu Yu,Xun Sun,Yang Liu,Yiming Dou,Ye Tian,Yiming Zhang,Genghao Wang,Lianyong Wang,Jianmin Han,Xiaohong Li,Xigao Cheng,Honglong Li,Haobo Pan,Lei Yang,Yanhong Zhao,Qiang Yang

Focal articular cartilage defects often progress to osteoarthritis, imposing a substantial global health burden. Current neglect of cartilage developmental regulation and cartilage microenvironment compromises therapeutic efficacy. We developed an innovation CE-SKP/CPH/P2G3 scaffold which effectively repairs focal cartilage defects and emulates native cartilage ontogeny: the superficial CE-SKP hydrogel layer recruits SMSCs and promotes chondrogenesis; the middle CPH hydrogel layer induces chondrocyte hypertrophic calcification, forming cartilage calcified layer; and the basal P2G3 nanofiber membrane isolates subchondral cells, enforcing a top-down developmental sequence and preserving a localized hypoxic niche. In vitro characterization confirms that the porosity, swelling ratio, biodegradation rate, and biocompatibility are optimal for sequential SMSC recruitment, cartilage differentiation, hypertrophic mineralization, and cells isolation. In vivo , the biomimetic tri-layer scaffold promotes regeneration of both cartilage and calcified cartilage by recapitulating the native ontogenetic progression from cartilage to calcified cartilage within the in vivo microenvironment, successfully restoring the normal physiological structure of articular cartilage by 24 weeks post-implantation. ScRNA-seq revealed SMSCs and a novel chondrocyte subpopulation CHON_5 as key repair populations, SMSCs mediated early repair via hypoxia response and migration, while CHON_5 promoted ECM remodeling, synergistically enhancing regeneration in late repair stage. Furthermore, we identified FGF signaling (FGF2-FGFR1/2 and FGF18-FGFR1/2 pairs) was crucial for MSC-CHON_5 communication during sequential cartilage regeneration. Overall, by recapitulating native developmental dynamics and microenvironmental cues, this scaffold offers a novel and effective strategy for functional cartilage regeneration and osteoarthritis treatment.

CAS / MDL: 920-66-1
研究领域: 组织工程 · 再生医学 · 生物医学材料 · 发育生物学 · 骨科
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JOURNAL OF CONTROLLED RELEASE · 2025 · IF 11.5

A dual-modified glucomannan polysaccharide selectively sequesters growth factors for skin tissue repair

Xiaotong Hu,Daping Xie,Yuwei Li,Yiming Niu,Rongwei Tan,Zhending She,Chunming Wang

Artificial dermal matrixes (ADMs) are valuable clinical options for treating large soft tissue defects, but their suboptimal bioactivities compared with the real tissue limit their therapeutic potential. For example, glycosaminoglycan (GAG) polysaccharides in the native skin vitally and differentially regulate endogenous growth factors (GFs) to maintain tissue homeostasis. However, the GAG used in the current ADMs has often lost such delicate regulation. Here, we developed a novel polysaccharide-based ADM that can promote skin tissue repair through selective modulation of specific pro-healing GFs. First, we prepared a plant-derived backbone of glucomannan (named BSP) – representing the two dominant monosaccharide components in the human body – in mass and homogenic quality. Then, we modified this backbone with sulfate and acetyl groups in a controlled manner to yield an optimized BSP derivative (S M A L -BSP) as a main composition to generate a new ADM. In vitro, S M A L -BSP enabled the ADM to selectively sequester pro-angiogenic GFs of VEGF-A and FGF-2 in situ for stimulating endothelial cell growth. Moreover, the addition of the acetyl group induced macrophages to secrete nitric oxide (NO) with antibacterial activities. Further in vivo tests in a rat model of full-thickness skin wounds indicated that S M A L -BSP ADM could sequester GFs in situ to promote angiogenesis and thus tissue regeneration, with superior effects than conventional chondroitin sulfate-based ADM, while showing no adverse effects often associated with animal-derived products. Our study represents a novel strategy for ADM design, targeting selective GF sequestration towards optimal skin tissue regeneration.

研究领域: 组织工程 · 生物材料 · 伤口愈合 · 药剂学
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International Journal of Electrochemical Science · 2023 · IF 1.5

An enzyme-free electrochemical immunosensor based on MOF/SWCN nanocomposites for rapid and sensitive detection of fibroblast growth factor 21

Tianxiao Yu,Shikuan Hou,Xizhenzi Fan,Yanxia Qiao,Guohua Zhang,Lingli Wang,Jun Ge

In this work, an enzyme-free electrochemical immunosensor based on metal-organic framework (MOF) and single-wall carbon nanotube (SWCN) nanocomposite coated glassy carbon electrode (GCE) for rapid and sensitive detection of fibroblast growth factor 21 (FGF-21) was proposed. The synthesized MOF/SWCN were characterized by transmission electron microscopy (TEM). It exhibited high-speed charge mobility, excellent conductivity and high surface area, significantly amplifying the current signal response. Furthermore, to immobilize the FGF-21 capture antibody on the MOF/SWCN electrode surface in an ordered orientation, staphylococcal protein A (SPA) was introduced as a connecting element, which significantly increased the antigen-binding ability and immunosensor stability. Under optimal conditions, the wide linear range of the immunosensor was 1.00 pg mL -1 to 500 ng mL -1 , with a low detection limit was 0.35 pg mL -1 . Additionally, the immunosensor also showed excellent reproducibility and selectivity. It was also successfully used to detect FGF-21 in human serum samples with satisfying recoveries. Thus, the strategy provides a simple and sensitive method for FGF-21 detection, indicating significant potential applications in clinical diagnostics.

CAS / MDL: 68-12-2 64-18-6
研究领域: 电化学 · 纳米技术 · 生物传感器 · 临床诊断 · 分析化学
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Stem Cell Research & Therapy · 2022 ·Vol. 13 ·期 1 ·1-16 · IF 8.079

Identification of a new way to induce differentiation of dermal fibroblasts into vascular endothelial cells

Cui XiaoLing,Wang XiaoTan,Wen Jie,Li Xiao,Li Nan,Hao XuXiao,Zhao BaoXiang,Wu Xunwei,Miao JunYing

Background Human dermal fibroblasts (HDFs) have the potential to differentiate into vascular endothelial cells (VECs), but their differentiation rate is low and the mechanism involved is not clear. The small molecule pathway controls the phenotype of fibroblasts by activating cellular signaling pathways, which is a more convenient method in the differentiation strategy of HDFs into VECs. Methods In this study, HDFs were treated with the different doses of CPP ((E)-4-(4-(4-(7-(diethylamino)-2-oxo-2H-chromene-3-carbonyl) piperazin-1-yl) styryl)-1-methylpyridin-1-ium iodide), and the mRNA and protein levels of HDFs were detected by qPCR, Western blot, flow cytometry and immunofluorescent staining. The matrigel assays, acetylated-LDL uptake and angiogenesis assays of chick embryo chorioallantoic membrane (CAM) and hindlimb ischemia model of nude mice were performed to evaluate the functions of VECs derived from HDFs. Results Here, we report that the small chemical molecule, CPP, can effectively induce HDFs to differentiate into VECs. First, we observed the morphological changes of HDFS treated with CPP. Flow cytometry, Western blot and qRT-PCR analyses showed that CPP effectively decreased the level of the HDFs-marker Vimentin and increased levels of the VEC-markers CD31, CD133, TEK, ERG, vWF, KDR and CDH5. Detection of the percentage of CD31-positive cells by immunofluorescent staining confirmed that CPP can effectively induce HDFs to differentiate into VECs. The results of Matrigel assays, DiI-ac-LDL uptake, angiogenesis assays on CAM and hindlimb ischemia model of nude mice showed that CPP-induced HDFs have the functions of VECs in vitro and in vivo. Western blot and qRT-PCR analysis showed that CPP induces HDFs to differentiate into VECs by promoting the expression of pro-angiogenic factors (VEGF, FGF-2 and PDGF-BB). Conclusions Our data suggest that the small chemical molecule CPP efficiently induces the differentiation of HDFs into VECs. Simultaneously, this new inducer provides a potential to develop new approaches to restore vascular function for the treatment of ischemic vascular diseases.

CAS / MDL: 3520-42-1
研究领域: 细胞生物学 · 分子生物学 · 血管生物学 · 再生医学
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CARBOHYDRATE POLYMERS · 2021 · IF 9.381

Chondroitin sulfate zinc with antibacterial properties and anti-inflammatory effects for skin wound healing

Guofeng Wu,Fenbo Ma,Yizhebang Xue,Ying Peng,Liqiu Hu,Xiaowo Kang,Qili Sun,Dong Fang Ouyang,Bin Tang,Lijun Lin

A chondroitin sulfate zinc (CSZn) complex was prepared by an ion-exchange method. The purified product was characterized by energy-dispersive X-ray spectroscopy, high-performance chromatography, elemental analysis , Fourier transform infrared spectroscopy , inductively coupled mass spectrometry , and nuclear magnetic resonance spectroscopy . The CSZn demonstrated antibacterial activity against Escherichia coli and Staphylococcus aureus and satisfied MTT cell viability (NIH3T3 fibroblasts) at ≤50 μg/mL. RT-PCR demonstrated significant promotion by CSZn of fibroblast growth factor beta (β-FGF), collagen III (COLIIIα1), vascular endothelial growth factor (VEGF) and reduction of cytokines IL-6, IL-1β & TNF-alpha. An in vivo rat full-thickness wound healing model demonstrated significant wound healing of CSZn relative to controls of saline treatment, zinc chloride treatment and chondroitin treatment. CSZn has demonstrated promising antibacterial and wound healing properties making it deserving of consideration for more advanced wound healing applications.

CAS / MDL: 9007-28-7
研究领域: 药学 · 伤口愈合 · 生物材料 · 生物医学工程 · 微生物学 · 细胞生物学
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