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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2022 ·Vol. 23 ·期 3 ·1249 · IF 6.208

Chitosan/Alginate Hydrogel Dressing Loaded FGF/VE-Cadherin to Accelerate Full-Thickness Skin Regeneration and More Normal Skin Repairs

Lai Wei,Jianying Tan,Li Li,Huanran Wang,Sainan Liu,Junying Chen,Yajun Weng,Tao Liu

The process of full-thickness skin regeneration is complex and has many parameters involved, which makes it difficult to use a single dressing to meet the various requirements of the complete regeneration at the same time. Therefore, developing hydrogel dressings with multifunction, including tunable rheological properties and aperture, hemostatic, antibacterial and super cytocompatibility, is a desirable candidate in wound healing. In this study, a series of complex hydrogels were developed via the hydrogen bond and covalent bond between chitosan (CS) and alginate (SA). These hydrogels exhibited suitable pore size and tunable rheological properties for cell adhesion. Chitosan endowed hemostatic, antibacterial properties and great cytocompatibility and thus solved two primary problems in the early stage of the wound healing process. Moreover, the sustained cytocompatibility of the hydrogels was further investigated after adding FGF and VE-cadherin via the co-culture of L929 and EC for 12 days. The confocal 3D fluorescent images showed that the cells were spherical and tended to form multicellular spheroids, which distributed in about 40–60 μm thick hydrogels. Furthermore, the hydrogel dressings significantly accelerate defected skin turn to normal skin with proper epithelial thickness and new blood vessels and hair follicles through the histological analysis of in vivo wound healing. The findings mentioned above demonstrated that the CS/SA hydrogels with growth factors have great potential as multifunctional hydrogel dressings for full-thickness skin regeneration incorporated with hemostatic, antibacterial, sustained cytocompatibility for 3D cell culture and normal skin repairing.Keywords:hydrogel dressing;full-thickness skin regeneration;3D cell culture;FGF;VE-cadherin

CAS / MDL: 9012-76-4
研究领域: 生物医学工程 · 组织工程 · 伤口愈合
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EUROPEAN JOURNAL OF PHARMACOLOGY · 2020 · IF 3.263

Involvement of FGF-2 modulation in the antidepressant-like effects of liquiritin in mice

Min Chen,Qiu-Ping Zhang,Ji-Xiao Zhu,Jie Cheng,Qing Liu,Guang-Hui Xu,Cheng-Fu Li,Li-Tao Yi

It has been reported that liquiritin produced an antidepressant-like effect in rodents. However, little information is known regarding its antidepressant activity with the regulation of fibroblast growth factor 2 (FGF-2), a protein maintaining development and maturation of the nervous central system . Therefore, the aim of the present study was to investigate the underlying FGF-2 modulation involved in the antidepressant-like effects of liquiritin. In the present study, mice were orally administrated with liquiritin for 7 days prior to LPS injection. The depressive-like behaviors , levels of FGF-2, number of Iba1 positive cells, expression of proinflammatory cytokines and density of dendritic spines were evaluated. The results showed that liquiritin significantly ameliorated the depressive-like behaviors in mice response to LPS injection. Liquiritin reversed the reduction of FGF-2 levels in the hippocampus of LPS induced mice. In addition, the microglial activation caused by LPS was attenuated by liquiritin, in accordance with downregulation in mRNA levels of proinflammatory cytokines. Moreover, liquiritin also increased the density of dendritic spines in the hippocampus, which was suppressed by LPS. In conclusion, our findings demonstrated that liquiritin exerted the antidepressant-like effects in LPS-induced depression through FGF-2 enhancement by inhibiting neuroinflammation and maintaining synaptogenesis .

研究领域: 药理学 · 神经科学 · 免疫学
✓ 已验证 DOI PubMed 高影响因子
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PHYTOMEDICINE · 2020 · IF 4.268

Cyanidin-related antidepressant-like efficacy requires PI3K/AKT/FoxG1/FGF-2 pathway modulated enhancement of neuronal differentiation and dendritic maturation

Xin Shan,Jing Chen,Shilin Dai,Jie Wang,Zhiheng Huang,Zhiyang Lv,Qian Wang,Qinan Wu

Background Cyanidin (CY) is one of the most abundant anthocyanidins found in red-purple diet sources such as grapes, blueberries and purple corns . CY has been proven to exhibit a wide range of biological functions including antioxidant, antiviral, anticarcinogenic and anti-inflammatory properties. Purpose This study investigated the anti-depressive activity of CY and its related mechanism. Methods In the behavioral tests, CY-related effects on depressive symptoms were evaluated. Then the changes in PI3K/AKT/FOXG1/FGF-2 signaling and adult neurogenesis including doublecortin (DCX+) cell number, dendritic length, secondary and third dendrites number in the hippocampus were investigated by Immunofluorescence and Western blot analyses. PI3K antagonist LY 294,002 was used to verify the unique impact of PI3K/AKT/FoxG1/FGF-2 signaling on CY-related antidepressant efficacy. Results CY grossly reversed CUMS-induced behavioral defects, The DCX+ cell number and protein levels increased in CUMS mice receiving CY administration. LY 294,002 successfully blocked CY-induced improvements in depressive behaviors, neurogenesis, and protein levels in CUMS mice. Conclusion The findings demonstrated that CY was efficacious in alleviating depression-like symptoms, which was dependent on PI3K/AKT/FoxG1/FGF-2 signaling-modulated neurogenesis enhancement.

CAS / MDL: 54910-89-3
研究领域: 药理学 · 神经科学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF ETHNOPHARMACOLOGY · 2021 · IF 4.36

Paeoniflorin exerts antidepressant-like effects through enhancing neuronal FGF-2 by microglial inactivation

Jie Cheng,Min Chen,Hui-Qi Wan,Xue-Qin Chen,Cheng-Fu Li,Ji-Xiao Zhu,Qing Liu,Guang-Hui Xu,Li-Tao Yi

Ethnopharmacological relevance Paeonia lactiflora is a famous Traditional Chinese medicine widely used for immunological regulation. Paeoniflorin , the main component of Paeonia lactiflora , exerts neuroprotective and antidepressant-like effects in rodents. Aim of the study Fibroblast growth factor 2 (FGF-2) is essentially required in the central nervous system as it acts as both a neurotrophic factor and an anti-inflammatory factor participating in the regulation of proliferation, differentiation and apoptosis of neurons in the brain. However, it is unclear whether paeoniflorin could exert antidepressant effects via regulating FGF-2. Materials and methods In the present study, the effects of paeoniflorin were evaluated in depressive mice induced by the endotoxin lipopolysaccharide (LPS) injection. Results The results showed that paeoniflorin markedly increased sucrose preference and reduced immobility time in LPS mice, indicating antidepressant effects. Consistent with the results from molecular docking showing paeoniflorin antagonizes TLR4 , NF-κB and NLRP3, the biochemical analysis also indicated paeoniflorin inhibited TLR4/NF-κB/NLRP3 signaling, decreased proinflammatory cytokine levels and microglial activation in the hippocampus of LPS induced mice. In addition, the levels of neuronal FGF-2 and the density of dendritic spine were improved by paeoniflorin. More importantly, the FGFR1 inhibitor SU5402 prevented the antidepressant effects of paeoniflorin and blocked the neuroinflammatory and neurogenic regulatory effects of paeoniflorin, indicating that FGF-2/FGFR1 activation was required for the effects of paeoniflorin. Conclusion Taken together, the results demonstrate that paeoniflorin exhibits neuroprotective and antidepressant effects in mice, which may be mediated by activating neuronal FGF-2/FGFR1 signaling via the inhibition of microglial activation in the hippocampus.

研究领域: 药理学 · 神经科学 · 免疫学 · 中医
✓ 已验证 DOI PubMed 高影响因子
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Materials Today Bio · 2026 · IF 11

Injectable self-healing polysaccharide hydrogel with slow-release b-FGF for adipose tissue regeneration

Shuhan Wu,Wenjun Shu,Xulong Zhu,Yong Mei Chen,Zhenxiu Liu,Yue Wang,Hengtao Song,Dong Xiao,Chao Zhai,Nan Jiang,Jianhui Li

b-FGF and an autologous adipose tissue suspension were incorporated into the self-healing injectable hydrogel through a Schiff base reaction to crosslink carbohydrazide-modified gelatin (Gel-CDH) and oxidized hyaluronic acid (OHA). • The b-FGF@OHA/Gel-CDH hydrogel demonstrated advantageous mechanical properties, injectability, self-healing ability, microstructural integrity, and biocompatibility. • The bioactive hydrogel with slow release of b-FGF promotes adipogenesis in vitro and in vivo . Soft tissue defects require the application of adipose tissue reconstruction techniques; however, these approaches often face challenges such as low survival rates due to mechanical pressure and inadequate blood supply. This study presents the development of an injectable, self-healing polysaccharide hydrogel designed for the slow release of basic fibroblast growth factor (b-FGF) that utilizes oxidized hyaluronic acid (OHA) and carbohydrazide-modified gelatin (Gel-CDH) as foundational components. The hydrogel is characterized by an optimal pore size, porosity, mechanical properties, and degradation behavior, in addition to excellent biocompatibility, all of which facilitate adipose tissue growth. In vitro experiments revealed that the OHA/Gel-CDH polysaccharide hydrogel significantly enhanced the adipogenic differentiation of adipose-derived stem cells. Furthermore, the implantation of the polysaccharide hydrogel in conjunction with an autologous fat graft suspension into the subcutaneous of the rat dorsal region resulted in improved adipose tissue survival and the regeneration of vascularized adipose tissue. These results suggest that the use of an injectable, self-healing OHA/Gel-CDH polysaccharide hydrogel with slow-released b-FGF in combination with autologous fat grafting is a promising strategy for the repair of soft tissue defects.

✓ 已验证 DOI 高影响因子
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Biomaterials Advances · 2022 · IF 0

Polydopamine modified acellular dermal matrix sponge scaffold loaded with a-FGF: Promoting wound healing of autologous skin grafts

Lianglong Chen,Jun Ma,Yujia Chen,Chaoyang Huang,Zijun Zheng,Yanbin Gao,Ziwei Jiang,Xuerong Wei,Yujie Peng,Shengxiang Yu,Lei Yang

Despite increasing potentials as a skin regeneration template (DRT) to guide tissue healing, acellular dermal matrix (ADM) is still challenged by issues (like dense architecture, low cellular adhesion and poor vascularization), contributing to necrosis and shedding of upper transplanted skins. Modified with polydopamine (PDA), a novel and porous DRT capable of drug delivery was designed using porcine-derived ADM (PADMS) gels, termed PDA-PADMS. However, it was unclear whether it could efficiently deliver human acidic fibroblast growth factor (a-FGF) and regenerate skin defects. Herein, after being fabricated and optimized with PADMS gels in different ratios (1:6, 1:7, 1:8), PDA-PADMS loading a-FGF (PDA-PADMS-FGF) was evaluated by the morphology, physical& chemical properties, drug release and in-vitro biological evaluations, followed by full-thickness skin defects implanted with PDA-PADMS-FGF covered by transplanted skins. Apart from containing abundant collagen and elastin, porous PADMS (with a loose and uniform structure) was demonstrated to possess controlled release of a-FGF and biocompatibility attributed to PDA coating. Consistent with augmented cellular migration and proliferation in vitro, PDA-PADMS-FGF also accelerated wound healing and reduced scarring, improving collagen arrangement and neovascularization. In conclusion, PDA-PADMS-FGF has a good potential and application prospect as a matrix material for wound repair.

研究领域: 组织工程 · 伤口愈合 · 生物医用材料 · 药物递送系统 · 再生医学
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JOURNAL OF POLYMER SCIENCE · 2026 · IF 3.9

Mechanical Reinforcement and Warpage Mitigation of FGF 3D-Printed High-Density Polyethylene Composites by Incorporating Vinyl-Functionalized Carbon Fiber

Junqing Liu,Youqiang Yao,Shanglin Xiao,Bin Wang,Shanling Chen,Xiping Li

High-density polyethylene (HDPE) composites face severe warpage in fused granular fabrication (FGF) 3D printing due to crystallization shrinkage and poor fiber-matrix compatibility. Herein, vinyl-functionalized carbon fiber (mCF) was prepared via desizing, oxidation, and silane grafting to reinforce HDPE/POE blends. The modification enhanced interfacial adhesion, reduced porosity, and promoted formation of a percolated filler network, as confirmed by SEM, FTIR, and rheology. Compared to raw CF composites, mCF systems exhibited higher storage modulus, lower tanδ , and improved stress transfer, leading to superior mechanical strength and thermal resistance. Notably, warpage was significantly suppressed at moderate loadings, while high mCF content caused viscosity-driven porosity increase. The 12.4 wt% mCF composite achieved balanced reinforcement and dimensional stability. This work demonstrates that interfacial engineering via silane coupling is an effective strategy to mitigate warpage and enhance performance of polyolefin-based 3D-printed components. Graphical Surface engineering reconstructs the carbon fiber/polyethylene interface, as confirmed by FTIR, TGA, and SEM analyses, resulting in enhanced interfacial adhesion and efficient stress transfer. The interconnected carbon-fiber framework provides a multiscale thermo-mechanical constraint that suppresses shrinkage-induced deformation, leading to outstanding dimensional stability, superior mechanical performance, and near-zero warpage in extrusion-based 3D printed polyethylene composites.

CAS / MDL: 7722-84-1 78-08-0
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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS · 2025 ·Vol. 113 ·期 1 ·e35533 · IF 3.4

Chitosan/Alginate-Based Hydrogel Loaded With VE-Cadherin/FGF as Scaffolds for Wound Repair in Different Degrees of Skin Burns

Sainan Liu,Lai Wei,Jinquan Huang,Jiayan Luo,Yajun Weng,Junying Chen

Burns are complex traumatic injuries that lead to severe physical and psychological problems due to the prolonged healing period and resulting physical scars. Owing to their versatility, hydrogels can be loaded with various functional factors, making them promising wound dressings. However, many hydrogel dressings cannot support cell survival for a long time, thereby delaying the process of tissue repair. Herein, based on chitosan (CS)/alginate (SA)/poly(ethylene glycol) diacrylate (PEGDA), a basic hydrogel with hemostasis and antibacterial properties was prepared, and loaded with vascular endothelial cadherin (VE-cadherin) and fibroblast growth factors (FGF) to promote the co-culture of various skin cells, suitable for treating various skin injury types: (1) Construct a three-dimensional microenvironment conducive to the release of drugs and factors using natural biological macromolecules CS/SA. (2) Promote the cell growth by loading growth factors. (3) Establish skin burn models of different degrees and observe the repair process. From the results, the 3D microenvironment provided by hydrogel could support the active growth of cells for 12 days. Furthermore, deep burns with full-thickness skin were substantially repaired within about 24 days. Collectively, CS/SA hydrogel containing VE-cadherin and FGF can promote tissue healing in wounds with necrotic tissue, making it an ideal candidate for burn treatment.

CAS / MDL: 9012-76-4
研究领域: 生物医学工程 · 组织工程 · 伤口愈合 · 生物材料科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Nature Communications · 2025 ·Vol. 16 ·期 1 ·1-17 · IF 15.7

Heparan sulfate regulates myofibroblast heterogeneity and function to mediate niche homeostasis during alveolar morphogenesis

He Hua,Ma Chong,Wei Wei,Wang Haonan,Lai Yutian,Liu Ming,Sun Shenfei,Ma Qing,Lai Jiashuang,Liu Hanxiang,Liu Hanmin,Sun Fei,Lin Xinhua

Postnatal respiration requires bulk formation of alveoli that produces extensive surface area for gas diffusion from epithelium to the circulatory system. Alveolar morphogenesis initiates at late gestation or postnatal stage during mammalian development and is mediated by coordination among multiple cell types. Here we show that fibroblast-derived Heparan Sulfate Glycosaminoglycan (HS-GAG) is essential for maintaining a niche that supports alveolar formation by modulating both biophysical and biochemical cues. Gli1-CreER mediated deletion of HS synthase gene Ext1 in lung fibroblasts results in enlarged and simplified alveolar structures. Ablation of HS results in loss of a subset of PDGFRα hi αSMA + alveolar myofibroblasts residing in the distal alveolar region, which exhibit contractile properties and maintain WNT signaling activity to support normal proliferation and differentiation of alveolar epithelial cells. HS is essential for proliferation while preventing precocious apoptosis of alveolar myofibroblasts. We show that these processes are dependent upon FGF/MAPK signaling and forced activation of MAPK/ERK signaling partially corrected alveolar simplification and restored alveolar myofibroblast number and AT2 cell proliferation in HS deficient mice. These data reveal HS-dependent myofibroblast heterogeneity and function as an essential orchestrator for developing alveolar niche critical for the generation of gas exchange units.

研究领域: 发育生物学 · 细胞生物学 · 呼吸系统医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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American Journal of Translational Research · 2020 · IF 3.375

Three-dimensional-printed titanium alloy porous scaffold combined with trans-cinnamaldehyde for repairing osteonecrosis of the femoral head in a dog model

Runzi Gao,Wenhui Ji,Tianwei Xia,Yanxing Fan,Wei Wei,Le Shi,Jinzhu Liu,Chao Zhang,Lezhen Xue,Jirong Shen

Osteonecrosis of the femoral head (ONFH) is a common disorder that may be idiopathic, caused by trauma, or associated with alcohol or glucocorticoid use. The goals of early treatment include delaying or avoiding hip replacement, but there are no effective treatments for early-stage disease. The aim of the present study was to evaluate the effects of treatment with 3D-printed porous titanium alloy scaffold combined with daily intraperitoneal trans-cinnamaldehyde (TCA) in a dog model of ONFH. Four weeks after creation of the ONFH model, MRI examination of the femoral head showed the characteristic “double line sign” of ONFH, verifying the validity of our model. After another 12 weeks, femoral head specimens were harvested and examined by gross inspection; micro-computed tomography; histologic staining (hematoxylin and eosin; Masson); immunohistochemical analysis and quantitative real-time polymerase chain reaction analysis. Gross inspection of the femoral head in untreated ONFH animals at 16 weeks after model creation showed pale, exfoliating articular cartilage and disordered trabecular bone. Treatment with 3D-printed titanium alloy porous scaffold combined with TCA ameliorated the pathologic ONFH changes and significantly reduced inmature bone tissue as well as imature collagen in the femoral head, as shown by Masson staining. This treatment also increased VEGF, BMP2, β-catenin, b-FGF, and RUNX2 expression and decreased PPARγ expression, compared with untreated ONFH. In conclusion, 3D-printed titanium alloy porous scaffold combined with TCA can effectively improve ONFH, which may be related to local repair. This provides the theoretical basis for a new treatment strategy for ONFH.

CAS / MDL: 76-03-9
研究领域: 骨科 · 再生医学 · 药理学 · 生物医学工程
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Journal of Materials Chemistry B · 2020 ·Vol. 8 ·期 43 ·9921-9932 · IF 5.344

PLGA/chitosan–heparin composite microparticles prepared with microfluidics for the construction of hMSC aggregates

Min Ge,Yaqi Sheng,Shuyue Qi,Lei Cao,Yan Zhang,Jun Yang

Incorporating poly(lactic-co-glycolic) acid (PLGA) microparticles into human mesenchymal stem cells (hMSC) aggregates has shown promising application prospects. However, the acidic degradation products and burst release of PLGA microparticles still need to be ameliorated. In this study, the PLGA/chitosan–heparin (P/C–h) composite microparticles were successfully fabricated by integrating the double emulsion and microfluidic technology through the precise manipulation of the emulsion composition and flow rate of the two-phase in a flow-focusing chip. The P/C–h microparticles were highly monodispersed with a diameter of 23.45 ± 0.25 μm and shell–core structure of the PLGA encapsulated C–h complex, which were suitable for the fabrication of hMSC aggregates. When the mass ratio of PLGA to the C–h complex was optimized to 2 : 1, the pH of the leach liquor of P/C–h microparticles remained neutral. Compared with those of PLGA microparticles, the cytotoxicity and the initial burst release (loaded FGF-2 and VEGF) were both significantly reduced in P/C–h microparticles. Furthermore, the survival, stemness, as well as secretion and migration abilities of cells in hMSC aggregates incorporating P/C–h microparticles were also enhanced. In summary, the P/C–h composite microparticles prepared by the droplet microfluidic technique support the optimal biological and functional profile of the hMSC aggregates, which may facilitate the clinical applications of MSC-based therapy.

研究领域: 生物医学工程 · 组织工程 · 干细胞生物学 · 药物递送系统
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BIOMEDICINE & PHARMACOTHERAPY · 2023 · IF 7.5

Folium crataegi boosts skin regeneration for burn injury in rats through multiple ways

Zhihong Deng,Lifeng Zhao,Xiuxue Li,Chang-Yun Wang,Yue Zhou,Mengfei Li,Yingfei Li,Xianjun Fu

Appropriate topical dressings for burn treatments are important to accelerate skin wound recovery and prevent external infections. This study aimed to evaluate the effect and investigate the mechanism of folium crataegi ( Crataegus pinnatifida Bge. ) for the treatment of burn wounds, as well as to compare the therapeutic effects of aqueous extracts ( HLW ) and alcoholic extracts ( HLE ) from folium crataegi . The results demonstrated that both HLW and HLE groups exhibited a higher wound contraction rate than the silver sulfadiazine ( SSD ) ointment group. Moreover, HLW showed more significant wound repair effects than HLE . HLW significantly increased levels of EGF and FGF-2 in wound tissue, as well as TGF-β1 , VEGF , CAT and IL-10 in serum. Folium crataegi extract, especially aqueous extracts, exerted good anti-inflammatory, anti-oxidant and anti-bacterial effects by upregulating the expression of lag3 , txn1 and slpi , respectively. Folium crataegi extract significantly inhibits the expression of npas2 , a key gene in the circadian rhythm pathway. In conclusion, this research illustrated that the folium crataegi extract, especially aqueous extracts, had better therapeutic effects on skin burns through multiple ways, possibly including a novel mechanism related to circadian rhythm pathway. These findings suggest that folium crataegi could be a valuable source of compounds for enhancing skin regeneration through multiple ways.

研究领域: 药理学 · 烧伤治疗 · 伤口愈合 · 分子生物学 · 免疫学
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