Acta Biomaterialia
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2024
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IF 9.4
Yuye Huang,Kai Ye,Andong He,Shaobo Wan,Miaoben Wu,Donghao Hu,Kailei Xu,Peng Wei,Jun Yin
Peripheral nerve injuries (PNIs) can cause neuropathies and significantly affect the patient's quality of life. Autograft transplantation is the gold standard for conventional treatment; however, its application is limited by nerve unavailability, size mismatch, and local tissue adhesion. Tissue engineering, such as nerve guidance conduits, is an alternative and promising strategy to guide nerve regeneration for peripheral nerve repair; however, only a few conduits could reach the high repair efficiency of autografts. The healing process of PNI is frequently accompanied by not only axonal and myelination regeneration but also angiogenesis, which initializes nerve regeneration through vascular endothelial growth factor A (VEGF-A). In this study, a composite nerve conduit with a poly (lactic-co-glycolic acid) (PLGA) hollow tube as the outer layer and gelatin methacryloyl (GelMA) encapsulated with VEGF-A transfected Schwann cells (SCs) as the inner layer was established to evaluate its promising ability for peripheral nerve repair. A rat model of peripheral nerve defect was used to examine the efficiency of PLGA/GelMA-SC (VA) conduits, whereas autograft, PLGA, PLGA/GelMA, and PLGA/GelMA-SC (NC) were used as controls. VEGF-A-transfected SCs can provide a stable source for VEGF-A secretion. Furthermore, encapsulation in GelMA cannot only promote proliferation and tube formation of human umbilical vein endothelial cells but also enhance dorsal root ganglia and neuronal cell extension. Previous animal studies have demonstrated that the regenerative effects of PLGA/GelMA-SC (VA) nerve conduit were similar to those of autografts and much better than those of other conduits. These findings indicate that combination of VEGF-A-overexpressing SCs and PLGA/GelMA conduit-guided peripheral nerve repair provides a promising method that enhances angiogenesis and regeneration during nerve repair. Statement of significance Nerve guidance conduits shows promise for peripheral nerve repair, while achieving the repair efficiency of autografts remains a challenge. In this study, a composite nerve conduit with a PLGA hollow tube as the outer layer and gelatin methacryloyl (GelMA) encapsulated with vascular endothelial growth factor A (VEGF-A)-transfected Schwann cells (SCs) as the inner layer was established to evaluate its potential ability for peripheral nerve repair. This approach preserves growth factor bioactivity and enhances material properties. GelMA insertion promotes Schwann cell proliferation and morphology extension. Moreover, transfected SCs serve as a stable VEGF-A source and fostering angiogenesis. This study offers a method preserving growth factor efficacy and safeguarding SCs, providing a comprehensive solution for enhanced angiogenesis and nerve regeneration.
研究领域:
组织工程
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神经科学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Communications Biology
·
2021
·Vol. 4
·期 1
·1-14
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IF 6.268
Geng Yingnan,Duan Huichuan,Xu Liang,Witman Nevin,Yan Bingqian,Yu Zheyuan,Wang Huijing,Tan Yao,Lin Liqin,Li Dong,Bai Shanshan,Fritsche-Danielson Regina,Yuan Jie,Chien Kenneth,Wei Min,Fu Wei
Bone has a remarkable potential for self-healing and repair, yet several injury types are non-healing even after surgical or non-surgical treatment. Regenerative therapies that induce bone repair or improve the rate of recovery are being intensely investigated. Here, we probed the potential of bone marrow stem cells (BMSCs) engineered with chemically modified mRNAs (modRNA) encoding the hBMP-2 and VEGF-A gene to therapeutically heal bone. Induction of osteogenesis from modRNA-treated BMSCs was confirmed by expression profiles of osteogenic related markers and the presence of mineralization deposits. To test for therapeutic efficacy, a collagen scaffold inoculated with modRNA-treated BMSCs was explored in an in vivo skull defect model. We show that hBMP-2 and VEGF-A modRNAs synergistically drive osteogenic and angiogenic programs resulting in superior healing properties. This study exploits chemically modified mRNAs, together with biomaterials, as a potential approach for the clinical treatment of bone injury and defects.
研究领域:
再生医学
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组织工程
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分子生物学
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骨科
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产品关联
DOI
PubMed
高影响因子
iScience
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2023
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IF 5.8
Yating Xie,Wenya Guo,Xi Shen,Weina Yu,Yanping Kuang,Qiuju Chen,Hui Long,Qifeng Lyu,Li Wang
Summary Progestin-primed ovarian stimulation (PPOS) is a new ovulation stimulation protocol, and its role in ovulation and regulatory mechanism is unclear. The clinical PPOS protocol was simulated in mice. The ovulated oocytes, estradiol, progesterone, and luteinizing hormone (LH) levels were analyzed at different hours after trigger. mRNA extraction and real-time PCR, hematoxylin and eosin staining, and immunofluorescence of ovaries were used to explore the involved signaling pathways. The PPOS group had a delayed ovulation at 12.5 h after trigger. Its suppressed LH level reduced the expression of luteinizing hormone/choriogonadotropin receptor (LHCGR) on the preovulatory follicles before trigger and significantly decreased the following progesterone synthesis, blood progesterone level, and progesterone receptor (PGR) expression within 4–6 h after trigger. Furthermore, the important ovulatory genes regulated by PGR including ADAMTS-1, VEGF-A, and EDN2 were downregulated, ultimately delaying the ovulation. PPOS suppresses the LH level before trigger and decreases the synthesis of progesterone after trigger, thus delaying the ovulation by downregulating the LHCGR-PGR pathway.
研究领域:
生殖生物学
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内分泌学
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分子生物学
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DOI
PubMed
高影响因子
Oncology Letters
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2018
·Vol. 16
·期 2
·2289-2298
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IF 1.664
Chunyu Li,Qi Wang,Shen Shen,Xiaolu Wei,Guoxia Li
Metastasis is the primary cause of mortality in patients with breast cancer and lacks effective therapeutic agents. Oridonin, an active diterpenoid compound isolated from Rabdosia rubescens, was identified to be the most potent anti‑tumor ingredient. However, the molecular mechanisms responsible for its anti‑metastatic effects remain unclear. In the present study, oridonin significantly suppressed the migration, invasion and adhesion of MDA‑MB‑231 and 4T1 breast cancer cells, and inhibited tube formation of human umbilical vein endothelial cells in a dose‑dependent manner. The expression levels of epithelial‑mesenchymal transition (EMT)‑associated marker and the hypoxia inducible factor 1α (HIF‑1α)/vascular endothelium growth factor (VEGF) signaling pathway mRNA and proteins were determined by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively in vitro. The results demonstrated that oridonin effectively inhibited EMT as demonstrated by the significant increases in the expression levels of E‑cadherin, and decreased expression of N‑cadherin, Vimentin and Snail. In addition, oridonin exerted its anti‑angiogenesis activity through significantly decreasing HIF‑1α, VEGF‑A and VEGF receptor‑2 protein expression. Furthermore, oridonin was demonstrated to decrease the micro‑vessel density as evidenced by the decreased expression of cluster of differentiation 31, a marker for neovasculature. In brief, oridonin inhibits tumor cell migration, invasion and adhesion, as well as tumor angiogenesis, which are mediated by suppressing EMT and the HIF‑1α/VEGF signaling pathway. The results of the present study suggest that oridonin may be a promising anti‑metastatic agent in breast cancer treatment.
研究领域:
癌症生物学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2022
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IF 7.033
Wei Shang,Xin Zhao,Fan Yang,Dongyi Wang,Le Lu,Zihan Xu,Zhiming Zhao,Hui Cai,Junyi Shen
Background: Compared with traditional drugs, nanomaterial drugs have the benefits of improving the solubility, bioavailability, and absorption rate of insoluble drugs. Nanoporous complexes can increase the efficiency with which drugs can penetrate the blood-brain barrier and reach target organs. Ginsenoside Rg1 is an effective drug that promotes angiogenesis. Ginsenoside Rg1 composite nanoparticles were employed to induce the expression of several key epigenetic enzymes and then activate the VEGF and Notch pathways after the onset of ischemic brain lesions. Methods: We constructed nanoparticles to fully encapsulate the therapeutic drug (ginsenoside Rg1), which can be transferred into brain tissue via the receptor-mediated transfer of drug-encapsulated nanoparticles. Evaluation of the therapeutic effect of ginsenoside Rg1 complex nanovesicles (CNV) was performed by in vitro and in vivo experiments. Real-time polymerase chain reaction (RT- PCR), Western blot, immunohistochemistry staining (IHC), and Co-immunoprecipitation (co-IP) were employed to screen for epigenetic enzymes with an up-regulated expression post ginsenoside Rg1-CNV intervention. RNA sequencing, shRNA knockdown, and chromatin Immunoprecipitation (ChIP) sequencing were performed to detect the target genes of ginsenoside Rg1-CNV that regulate angiogenesis. Then, bioinformatic analysis was performed to investigate the mechanism of action of epigenetic modifying enzymes in regulating target genes. Results: The average of the synthesized ginsenoside Rg1-CNV was 203.78±6.83 nm, the polydispersion index was 0.135±0.007, and the Zeta potential was 23.13±1.65 mV. Through in vivo and in vitro experiments, we found that it promotes the proliferation, migration, and tubular formation of brain microvascular endothelial cells (BMECs). Meanwhile, the intervention of ginsenoside Rg1-CNV promoted the demethylation of H3K27me3 within the promoter region of VEGF-A and Jagged1 genes and reduced the H3K27me3 modification within this region. Conclusion: The ginsenoside Rg1 nanoparticles may be an available blood-brain barrier penetrating agent for ischemic stroke.
研究领域:
药理学
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神经科学
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分子生物学
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表观遗传学
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DOI
PubMed
高影响因子
Biomed Research International
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2022
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IF 3.246
Yan Xu,Mingwei Cheng,Peijun Zhu,Shuo Yang,Chunhua Lai,Shulan Xu
During bone tissue regeneration, neovascularization is critical, and the formation of a blood supply network is crucial for bone growth stimulation and remodeling. Previous studies suggest that bioelectric signals facilitate the process of angiogenesis. Owing to their biomimetic electroactivity, piezoelectric membranes have garnered substantial interest in the field of guided bone regeneration. Nevertheless, the knowledge of their influence due to varying surface potentials on the progression of angiogenesis remains ambiguous. Therefore, we proposed the preparation of an electroactive material, P(VDF-TrFE), and investigated its effects on the activity and angiogenic functions of human umbilical vein endothelial cells (HUVECs). The HUVECs were directly cultured on P(VDF-TrFE) membranes with different surface potentials. Subsequently, cell viability, proliferation, migration, tube formation, and expressions of related factors were assessed through appropriate assays. Our results revealed that the negative surface potential groups exerted differential effects on the modulation of angiogenesis in vitro. The P(VDF-TrFE) membranes with negative surface potential exhibited the greatest effect on cellular behaviors, including proliferation, migration, tube formation, and promotion of angiogenesis by releasing key factors such as VEGF-A and CD31. Overall, these results indicated that the surface potential of piezoelectric P(VDF-TrFE) membranes could exert differential effects on angiogenesis in vitro. We present a novel approach for designing bioactive materials for guided bone regeneration.
研究领域:
生物材料
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组织工程
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再生医学
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细胞生物学
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生物医学工程
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DOI
PubMed
高影响因子
Advanced Science
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2024
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IF 14.3
Lanlan Zong,Runxin Teng,Huiqi Zhang,Wenshang Liu,Yu Feng,Zhengmao Lu,Yuxiao Zhou,Zhen Fan,Meng Li,Xiaohui Pu
Despite advancements in therapeutic agents for diabetic chronic wounds, challenges such as suboptimal bioavailability, intricate disease milieus, and inadequate delivery efficacy have impeded treatment outcomes. Here, ultrasound-responsive hydrogel incorporated with heparin-binding domain (HBD) peptide nanoparticles is developed to promote diabetic wound healing. HBD peptide, derived from von Willebrand Factor with angiogenic activity, are first engineered to self-assemble into nanoparticles with enhanced biostability and bioavailability. Ultrasound responsive cargo release and hydrogel collapses are first verified through breakage of crosslinking. In addition, desired antioxidant and antibacterial activity of such hydrogel is observed. Moreover, the degradation of hydrogel under ultrasound stimulation into smaller fragments facilitated the deeper wound penetration of ≈400 µm depth. Complete wound closure is observed from diabetic mice with chronic wounds after being treated with the proposed hydrogel. In detail, in vivo studies revealed that hydrogels loaded with HBD peptide nanoparticles increased the levels of angiogenesis-related growth factors (VEGF-A, CD31, and α-SMA) to effectively accelerate wound repair. Overall, this study demonstrates that ultrasound-responsive HBD peptide hydrogel provides a synergistic therapeutic strategy for external biofilm elimination and internal effective delivery for diabetic wounds with biofilm infection.
研究领域:
生物医学工程
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药学
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伤口愈合
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纳米技术
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生物材料
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2025
·
IF 11.5
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
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生物材料
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伤口愈合
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药剂学
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DOI
PubMed
高影响因子
Advanced Science
·
2023
·Vol. 10
·期 33
·2302622
·
IF 15.1
Yifan Ma,Lili Sun,Jingjing Zhang,Chi-ling Chiang,Junjie Pan,Xinyu Wang,Kwang Joo Kwak,Hong Li,Renliang Zhao,Xilal Y. Rima,Chi Zhang,Anan Zhang,Yutong Liu,Zirui He,Derek Hansford,Eduardo Reategui,Changsheng Liu,Andrew S. Lee,Yuan Yuan,Ly James Lee
Regenerative medicine in tissue engineering often relies on stem cells and specific growth factors at a supraphysiological dose. These approaches are costly and may cause severe side effects. Herein, therapeutic small extracellular vesicles (t-sEVs) endogenously loaded with a cocktail of human vascular endothelial growth factor A (VEGF-A) and human bone morphogenetic protein 2 (BMP-2) mRNAs within a customized injectable PEGylated poly (glycerol sebacate) acrylate (PEGS-A) hydrogel for bone regeneration in rats with challenging femur critical-size defects are introduced. Abundant t-sEVs are produced by a facile cellular nanoelectroporation system based on a commercially available track-etched membrane (TM-nanoEP) to deliver plasmid DNAs to human adipose-derived mesenchymal stem cells (hAdMSCs). Upregulated microRNAs associated with the therapeutic mRNAs are enriched in t-sEVs for enhanced angiogenic–osteogenic regeneration. Localized and controlled release of t-sEVs within the PEGS-A hydrogel leads to the retention of therapeutics in the defect site for highly efficient bone regeneration with minimal low accumulation in other organs.
研究领域:
再生医学
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组织工程
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干细胞生物学
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骨修复
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纳米技术
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）