CYTOTHERAPY
·
2025
·
IF 3.2
Jiaqi Lin,Ziwei Lin,Anqi Huang,Xinyi Wu,Wei Yan,Daojun Liu,Chiju Wei,Wencan Xu
Introduction The treatment of chronic refractory skin wounds still remains a serious clinical challenge. Stem cells and hydrogels are widely used in healing of skin wound of various types due to their superior bioactivities and biocompatibility. This study aimed to demonstrate the wound healing effect of a hydrogel compound loaded with enucleated stem cells expressing the platelet-derived growth factor (PDGF). Methods An injectable hydrogel was formulated using 22% poloxamer 407, 1% poloxamer 188 and 1% hyaluronic acid. A PDGF-B transgenic cell line of mouse bone marrow mesenchymal stem cells (BMSCs) was generated by lentiviral infection. Cells were enucleated and embedded in hydrogel. The healing effects of the compound was tested in a full-thickness skin wound model of Balb/c mice. The wound models were randomly divided into four groups: the control group applied with PBS buffer; the hydrogel group with hydrogel only; the BMSC group with hydrogel mixed with normal BMSCs; and the BMSC-PDGF group with hydrogel mixed with enucleated BMSCs expressing PDGF. Results Overexpression of PDGF-B in transgenic cell line of BMSCs was verified by RT-PCR, immunofluorescence staining and western blot. When enucleated, the viability measured by Calcein-AM staining reduced to 54.29% at 48 h. Conditioned medium was collected with or without hydrogel layered over cells. PDGF concentration measured by ELISA reached 14.66 ng/μL and 257.89 ng/μL respectively after 48-h cultivation, suggesting a possible slow releasing effect in the presence of hydrogel. When applied to the skin wound, the healing rates of the BMSC-PDGF group was significantly higher than that of the control group on day 3. BMSC-PDGF group had significantly more neovascularization and cutaneous appendages from day 7. The proliferation of collagen fibers in BMSC-PDGF group was significantly higher than the control group on day 3 and day 7. Finally, BMSC-PDGF group had significantly lower amount of the inflammatory factors TNF-α, IL-1β, IL-6, MMP-3 and MMP-9 than that of the control group on day 7. Conclusion PDGF-stem cell-hydrogel compound significantly improved wound healing and reduced wound inflammatory factor expression in Balb/c mice. This biomaterial-based approach provides a new powerful reference for the treatment of chronically wounded skin.
研究领域:
生物医学
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再生医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2024
·
IF 8
Susu Cui,Fan Wang,Weiwei Yang
Split aptamers have attracted extensive attention in sensing benefit of optimized concise structure and low-cost, but with lower binding affinity and stability. Here, we successfully engineer three pairs of split aptamers for PDGF-BB protein and develop a highly sensitive electrochemical sensor based on protein-templated split aptamer ligation reaction. The protein template directs the reassembly of split aptamers and accelerates the ligation reaction between azide and alkyne groups attached to the split fragments. The ligation yields of RS Split1 and RS Split2 with reserved binding sites are found to be 72.6 ± 1.8 % and 82.5 ± 1.3 %, respectively, while broken binding sites also obtain a ligation yield of 61.5 ± 2.1 % for BS Split3. We utilize the chemically modified split aptamers in place of the “capture” and “detection” antibodies used in ELISA, directly enabling the capture of electrochemically sensitive ligated aptamer to report target binding. This protein-templated ligation strategy improves the stability and sensitivity of the electrochemical sensor, with a low detection limit of 7 pM for PDGF-BB. The saturated electrochemical signal is approximately 3 times that of the non-ligated system. The proposed electrochemical sensor is also successfully applied to 50 % serum due to its excellent selectivity and bio-orthogonality. This strategy avoids the signal loss caused by traditional binding interruption during washing step via converting the ternary complex of aptamer/protein/aptamer to the binary complex of ligated aptamer/protein. This research offers a general sensing platform for other protein biomarkers and, more importantly, does not rely on expensive antibodies.
研究领域:
生物化学
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医学检测
·
分子诊断
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Zhuangzhuang Cai,Zhendong Mo,Qing Zhou,Xujie Zhou,Feng Huang,Jiaqi Jiang,Hang Li,Shunqing Tang
Chitosan-based hydrogels are considered to be ideal materials for promoting wound healing due to their nontoxic, biodegradable, and biocompatible properties. However, the weak mechanical strength, hemostatic properties, and adhesive properties of chitosan hydrogels limit their potential applications. In this study, we synthesized methacrylimide-chitosan (MAC)-4-arm polyethylene glycol (PEG)-dopamine (DMA) (MAC-PEG-DMA) hybrid hydrogels containing A-chain homodimers of platelet-derived growth factor (PDGF-AA) through one-pot photo-crosslinking. The resulting hydrogel exhibited improved mechanical strength and hemostatic properties as demonstrated by both in vitro blood clotting assay and rat liver hemorrhage assay. Furthermore, The PDGF-AA loaded hydrogel was also able to accelerate cell migration and proliferation. Data from skin wounds treated with this hybrid hydrogel showed faster wound closure and collagen maturation. Therefore, MAC-PEG-DMA (PDGF-AA) has great potential as a dressing to promote wound healing.
研究领域:
生物材料
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组织工程
·
伤口愈合
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
·
2018
·
IF 3.309
Yanting Zhu,Fangwei Li,Wenhua Shi,Cui Zhai,Jian Wang,Xin Yan,Qingting Wang,Qianqian Zhang,Lan Yang,Li Gao,Manxiang Li
Up-regulation of mammalian COP9 signalosome subunit 6 (CSN6) and consequent reduction of SCF ubiquitin ligase substrate receptor β-transduction repeat-containing protein (β-TrCP) have been shown to be associated with cancer cells proliferation . However, it is unclear whether CSN6 and β-TrCP are also involved in PDGF-induced pulmonary arterial smooth muscle cells (PASMCs) proliferation. This study aims to address this issue and further explore its potential mechanisms. Our results indicated that PDGF phosphorylated Akt, stimulated PASMCs proliferation; while inhibition of PDGF receptor (PDGFR) by imatinib prevented these effects. PDGF further up-regulated CSN6 protein expression , this was accompanied with β-TrCP reduction and increase of Cdc25A. Inhibition of PDGFR/PI3K/Akt signaling pathway reversed PDGF-induced such changes and cell proliferation. Prior transfection of CSN6 siRNA blocked PDGF-induced β-TrCP down-regulation, Cdc25A up-regulation and cell proliferation. Furthermore, pre-treatment of cells with MG-132 also abolished PDGF-induced β-TrCP reduction, Cdc25A elevation and cell proliferation. In addition, pre-depletion of Cdc25A by siRNA transfection suppressed PDGF-induced PASMCs proliferation. Taken together, our study indicates that up-regulation of CSN6 by PDGFR/PI3K/Akt signaling pathway decreases β-TrCP by increasing its ubiquitinated degradation, and thereby increases the expression of Cdc25A, which promotes PDGF-induced PASMCs proliferation.
研究领域:
细胞生物学
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分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2017
·
IF 8.402
Qiu Li,Yiming Niu,Huajia Diao,Lintao Wang,Xiuping Chen,Yitao Wang,Lei Dong,Chunming Wang
Recapitulating the typical features of extracellular matrix (ECM) in engineered biomaterials is crucial for preparing a suitable niche to activate endogenous tissue repair. Here, we report the design and evaluation of an ECM-mimetic scaffold that successfully accelerated wound healing through enriching endogenous platelet-derived growth factor-BB (PDGF-BB). Specifically, we prepared a electrospun hydrogel sponge (EGS) comprising a PDGF-BB-binding polysaccharide (EUP3) and gelatin. The two polymers in concert exerted a ‘retention-and-release’ function: upon the application of EGS in vivo , EUP3 started to bind and sequester endogenous PDGF-BB at the wound site; gradually, gelatin was degraded to free the PDGF-BB/EUP3 complex that acted on the cells in situ . Our serial in vitro and in vivo tests validated the efficacy of EGS in retaining PDGF-BB, releasing PDGF-BB/EUP3 in response to collagenase, and promoting various PDGF-BB-mediated regenerative activities. Particularly, EGS accelerated the repair of a full-thickness skin wound in mice and induced optimal neo-tissue formation, without the addition of any exogenous GFs, cells or genes. Collectively, our results suggest that, by mimicking the distinctive GF-affinitive feature of ECM, EGS as an engineered biomaterial can effectively harness the endogenous regenerative power of the native tissue. Our investigation may inspire the design of new, effective and safer approaches for tissue regeneration.
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
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伤口愈合
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2020
·Vol. 10
·期 32
·18601-18607
·
IF 3.119
Na Cheng,Yujie Liu,Omar Mukama,Xiaobo Han,Hualin Huang,Shuai Li,Peng Zhou,Xuewen Lu,Zhiyuan Li
Platelet-derived growth factor BB (PDGF-BB) is a potential biomarker of tumor angiogenesis. For the first time, we developed a highly sensitive aptasensor for PDGF-BB with an enhanced test line signal by using two different gold nanoparticles (AuNPs). Herein, we describe a highly sensitive biosensor for PDGF-BB detection that combines biotinylated aptamer on a sample pad and poly thymine-Cy3-AuNP-monoclonal antibody complexes against PDGF-BB immobilized on conjugate pad A. Streptavidin (SA) and rabbit anti-mouse polyclonal antibody were also immobilized in the nitrocellulose membrane at the test and control zones, respectively. When the target PDGF-BB protein was added, it first bound the aptamer, and later the monoclonal antibody to form a biotinylated complex that was captured by SA, resulting in a visual red line on the test zone. In addition, to enhance the sensitivity, another monoclonal antibody against Cy3 was conjugated on AuNP B and immobilized on conjugate pad B to form a AuNPs (A&B)-antibody-(PDGF-BB-Cy3)-aptamer-biotin-SA complex on the test line when a loading buffer was subsequently added. This approach showed a linear response to PDGF-BB from 3 ng mL−1 to 300 ng mL−1 with a limit of detection as low as 1 ng mL−1 obtained in 10 minutes. Our biosensor displayed results through red lines readable by the naked eye. Interestingly, our approach has been successfully applied for real sample verification, proving its applicability for cancer monitoring and diagnosis.
研究领域:
生物传感器
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纳米技术
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癌症诊断
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分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Fei Li,Chuwei Zhang,Xiaoping Zhong,Bo Li,Mengnan Zhang,Wanqian Li,Lifei Zheng,Xinghua Zhu,Shixuan Chen,Yi Zhang
Diabetic foot ulcers, pressure ulcers, and bedsores can easily develop into chronic wounds with bacterial infections, complicating wound healing. This work reports a two-step strategy for treating infected chronic wounds. Firstly, LL37 mimetic peptide-W379 peptides were rapidly released to eliminate the bacterial biofilm on the wound. Then, 3D radially aligned nanofiber scaffolds loaded with W379 antimicrobial peptide and PDGF-BB were used to treat the wound to prevent bacterial infection recurrence and promote angiogenesis and granulation tissue regeneration, thereby accelerating wound healing. In the presented study, we found that the combined use of burst and controlled release of W379 antimicrobial peptide effectively clears the bacterial biofilm and prevents the recurrence of bacterial infection. Additionally, we found that the removal of the bacterial biofilm contributed to modulating the local inflammatory response from a pro-inflammatory type to a pro-regenerative type. Furthermore, the use of PDGF-BB significantly promotes neovascularization and granulation tissue regeneration in the wound bed, resulting in accelerating re-epithelialization and wound closure. Our study provides a promising treatment method for the repair of infected chronic wounds.
研究领域:
生物医学工程
·
伤口愈合
·
组织工程
·
感染控制
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL BIOLOGY INTERNATIONAL
·
2019
·Vol. 44
·期 2
·402-411
·
IF 2.127
Guiling Zhu,Bin Ma,Penghong Dong,Junjun Shang,Xiaochuan Gu,Ying Zi
Melatonin has been reported to participate in bone metabolism in recent studies. However, the underlying mechanism in melatonin-mediated osteoblastic differentiation remains largely unknown. The aim of this study is to investigate the role of melatonin in osteoblastic differentiation. In the present study, additional melatonin significantly promoted osteoblastic differentiation of MC3T3-E1 cells as evidenced by increased messenger RNA (mRNA) levels of osteogenic markers, alkaline phosphatase (ALP), collagen type I α1 chain, osteocalcin, and runt-related transcription factor 2 (Runx2). It was noteworthy that the expression level of platelet-derived growth factor subunit B (PDGFB) and content of its homodimer PDGF-BB were remarkably increased after melatonin administration. Moreover, the mRNA levels of phosphorylated PDGFRβ (PDGF receptor β) and Akt, a serine/threonine-specific protein kinase, were significantly upregulated in melatonin-treated MC3T3-E1 cells determined by a real-time polymerase chain reaction. Besides, by performing alizarin red staining, osteoblastic differentiation of MC3T3-E1 cells was conspicuously promoted by melatonin, which could be partially attenuated by crenolanib, a PDGFR inhibitor. Similarly, results from immunofluorescence and western blot assay showed that melatonin-induced upregulation of Runx2 and phosphorylated Akt was suppressed by crenolanib. Akt inhibition by MK-2206 also suppressed osteoblastic differentiation. Furthermore, by in vivo assay, additional melatonin promoted osteoblastic differentiation in mice with femoral fracture, and obvious callus formation was observed in melatonin-treated mice 5 weeks after fracture. Melatonin supplement also inhibited osteoclastic differentiation in mice. All statistical analysis was performed using GraphPad Prism and a P < 0.05 was deemed to be significant. To summarize, we demonstrate that melatonin promotes osteoblastic differentiation in MC3T3-E1 cells and enhances fracture healing in mouse femoral fracture model and regulates PDGF/AKT signaling pathway.
研究领域:
骨骼生物学
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药理学
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细胞信号传导
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Ying Zhang,Shiqi Lin,Xiao Xu,Yufan Yao,Shufan Feng,Sida Jiang,Yuqian Wang,Wei He,Ran Mo
Dysregulation of growth factor expression causes impaired healing of diabetic foot ulcer (DFU). Platelet-derived growth factor (PDGF)-containing gel has been clinically applied for topical treatment of DFU. Recruitment of neutrophils stimulated by PDGF favors the wound healing of DFU. However, overactivation of neutrophils induced by hyperglycemia causes massive generation and long-term persistence of neutrophil extracellular traps (NETs), ultimately leading to unexpected skin damage and delayed wound repair. Here, we engineer a hierarchically-assembled hydrogel to achieve local release of the growth factor, PDGF-BB and the NET scavenger, deoxyribonuclease (DNase) I with distinct kinetics for enhanced healing of DFU. The hydrogel is constructed by crosslinking of anti-bacterial quaternized chitosan and hypochlorite-degradable nanogel via a copper-free click reaction, in which PDGF-BB is loaded in the hydrogel matrix while DNase I is encapsulated in the inner nanogel. Programmable release of combinatorial therapeutics is implemented by the hydrogel in response to the wound microenvironment. We show that the hierarchical hydrogel co-loaded with PDGF-BB and DNase I promotes neutrophil recruitment, increases endothelial cell migration, degrades excess NETs, and prevents wound infection for accelerating the wound closure in the diabetic mouse wound models.
研究领域:
生物材料学
·
医学工程
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2022
·
IF 6.911
Yusi Li,Fang Yang,Shunmei Li,Ruo Yuan,Yun Xiang
Proteins play vital roles in regulating a series of living activities and can be potentially considered to be useful indicators for diagnosing various diseases. Here, a target-triggered transcription cascade amplification strategy with the use of the fluorescence switch-on RNA aptamer is constructed for label-free and sensitive platelet-derived growth factor-BB (PDGF-BB) protein biomarker detection. The target molecule of PDGF-BB binds a rationally designed multifunctional hairpin probe to switch its structure and to expose a primer binding region. The primer sequence further binds such a region to initiate the target recycling and lighting-up RNA aptamer transcription cascade cycles to yield tremendous RNA aptamers. And, the fluorescence of the organic dye is substantially enhanced upon binding to these RNA aptamers for realizing highly sensitive and label-free PDGF-BB detection with the detection limit being lowered to 0.8 pM. Moreover, the developed strategy has superior selectivity and exhibits a promising potential to detect PDGF-BB spiked into serums with buffer dilution, which makes this method an attractive sensing system for detecting other biomarkers at trace levels.
研究领域:
生物化学
·
分子生物学
·
医学诊断
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2017
·
IF 4.3
Yanyan Yu,Gaoxing Su,Hongyan Zhu,Qing Zhu,Yong Chen,Bohui Xu,Yuqin Li,Wei Zhang
In this study, we fabricated a novel electrochemical biosensing platform on the basis of target-triggered proximity hybridization-mediated isothermal exponential amplification reaction (EXPAR) for ultrasensitive protein analysis. Through rational design, the aptamers for protein recognition were integrated within two DNA probes. Via proximity hybridization principle, the affinity protein-binding event was converted into DNA assembly process. The recognition of protein by aptamers can trigger the strand displacement through the increase of the local concentrations of the involved probes. As a consequence, the output DNA was displaced, which can hybridize with the duplex probes immobilized on the electrode surface subsequently, leading to the initiation of the EXPAR as well as the cleavage of duplex probes. Each cleavage will release the gold nanoparticles (AuNPs) binding sequence. With the modification of G-quadruplex sequence, electrochemical signals were yielded by the AuNPs through oxidizing 3,3′,5,5′-tetramethylbenzidine in the presence of H2O2. The study we proposed exhibited high sensitivity toward platelet-derived growth factor BB (PDGF-BB) with the detection limit of 52 fM. And, this method also showed great selectivity among the PDGF isoforms and performed well in spiked human serum samples.
研究领域:
生物化学
·
分析化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2017
·
IF 5.401
Jing Zheng,Min Zhang,Xiaohui Guo,Jianping Wang,Jingli Xu
In this paper, we present a novel multifunctional magnetic composite with sandwich-like nanostructure, which is composed of a yolk-egg-like magnetic silica core and a continuous polydopamine(PDA)-Au coating. Firstly, yolk-egg-like magnetic composite(SiO 2 @Fe 3 O 4 @PDA) was prepared by a combined high temperature decomposition method with mussel chemistry. Then, Au nanoparticles(NPs) were in-situ generated on the surface of the SiO 2 @Fe 3 O 4 @PDA by reaction between the PDA shell and HAuCl 4 , forming a multilayer sandwich-like nanostructure. Benefiting from the good affinity of the PDA shell and Au NPs with thiol group, the 4-mercaptophenylboronic acid was successfully assembled on the surface of Au NPs and PDA layer. The hybrid magnetic composite functionalized with boronic acid was used as affinity probes to selectively capture PDGF from solution. Meanwhile, methylene blue(MB)-doped silica NPs (SiO 2 -MB) were prepared to immobilize aptamer. In the presence of PDGF, the aptamer labeled SiO 2 -MB (SiO 2 -MB-aptamer) specifically bound with the PDGF protein. By monitoring the change of the electrochemical signal of MB, we were able to detect the binding events between the aptamer and PDGF in homogeneous solutions. The sensor was highly selective and sensitive with a detection limit of 0.22 fM for PDGF. The developed method showed wide potential applications in protein monitoring and cancer diagnosis.
研究领域:
生物化学
·
纳米技术
·
分析化学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）