MOLECULES
·
2024
·Vol. 29
·期 8
·1832
·
IF 4.2
Pin Luo,Wei Liu,Zhangyao Ye,Yuyu Zhang,Zekun Zhang,Jing Yi,Rong Zeng,Shenyu Yang,Mei Tu
Diabetic wound healing is a significant clinical challenge because abnormal immune cells in the wound cause chronic inflammation and impair tissue regeneration. Therefore, regulating the behavior and function of macrophages may be conducive to improving treatment outcomes in diabetic wounds. Herein, sulfated chitosan (26SCS)-containing composite sponges (26SCS-SilMA/Col-330) with well-arranged layers and high porosity were constructed based on collagen and silk fibroin, aiming to induce an appropriate inflammatory response and promote angiogenesis. The results indicated that the ordered topological structure of composite sponges could trigger the pro-inflammatory response of Mφs in the early stage, and rapid release of 26SCS in the early and middle stages (within the concentration range of 1–3 mg/mL) induced a positive inflammatory response; initiated the pro-inflammatory reaction of Mφs within 3 days; shifted M1 Mφs to the M2 phenotype within 3–7 days; and significantly up-regulated the expression of two typical angiogenic growth factors, namelyVEGFandPDGF-BB, on day 7, leading to rapid HUVEC migration and angiogenesis. In vivo data also demonstrated that on the 14th day after surgery, the 26SCS-SilMA/Col-330-implanted areas exhibited less inflammation, faster re-epithelialization, more abundant collagen deposition and a greater number of blood vessels in the skin tissue. The composite sponges with higher 26SCS contents (the (5.0) 26SCS-SilMA/Col-330 and the (7.5) 26SCS-SilMA/Col-330) could better orchestrate the phenotype and function of Mφs and facilitate wound healing. These findings highlight that the 26SCS-SilMA/Col-330 sponges developed in this work might have great potential as a novel dressing for the treatment of diabetic wounds.
研究领域:
生物医学工程
·
组织工程
·
伤口愈合
·
炎症
·
血管生成
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Zhao Jian,Zhang Haoqian,Ling Zhengyun,An Ziyan,Xiao Shuwei,Wang Pengchao,Fu Zhouyang,Shao Jinpeng,Sun Yanfeng,Fu Weijun
Bladder tissue engineering holds promise for addressing bladder defects resulting from congenital or acquired bladder diseases. However, inadequate vascularization significantly impacts the survival and function of engineered tissues after transplantation. Herein, a novel bilayer silk fibroin (BSF) scaffold was fabricated with the capability of vascular endothelial growth factor (VEGF) and platelet derived growth factor-BB (PDGF-BB) sequential release. The outer layer of the scaffold was composed of compact SF film with waterproofness to mimic the serosa of the bladder. The inner layer was constructed of porous SF matrix incorporated with SF microspheres (MS) loaded with VEGF and PDGF-BB. We found that the 5% (w/v) MS-incorporated scaffold exhibited a rapid release of VEGF, whereas the 0.2% (w/v) MS-incorporated scaffold demonstrated a slow and sustained release of PDGF-BB. The BSF scaffold exhibited good biocompatibility and promoted endothelial cell migration, tube formation and enhanced endothelial differentiation of adipose derived stem cells (ADSCs) in vitro. The BSF patch was constructed by seeding ADSCs on the BSF scaffold. After in vivo transplantation, not only could the BSF patch facilitate the regeneration of urothelium and smooth muscle, but more importantly, stimulate the regeneration of blood vessels. This study demonstrated that the BSF patch exhibited excellent vascularization capability in bladder reconstruction and offered a viable functional bioengineered patch for future clinical studies.
研究领域:
组织工程
·
生物医学工程
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2022
·Vol. 50
·期 3
·1-13
·
IF 5.314
Zhen Shen,Wei Dong,Zehua Chen,Guoqian Chen,Yan Zhang,Zige Li,Haixiong Lin,Huamei Chen,Minling Huang,Ying Guo,Ziwei Jiang
Total flavonoids of Rhizoma Drynariae (TFRD), extracted from the kidney‑tonifying Traditional Chinese medicine Rhizoma Drynariae, can be effective in treating osteoporosis, bone fractures and defects. However, the pharmacological effects of TFRD on the specific vessel subtype CD31hiEmcnhi during distraction osteogenesis (DO) remains unclear. The present study aimed to investigate the effects of TFRD on CD31hiEmcnhi vessels in a rat model of DO. In the present study, tibial DO models were established using 60 rats with a distraction rate of 0.2 mm per day for 20 days. Co‑immunofluorescence staining of CD31 and endomucin (Emcn) was conducted to determine CD31hiEmcnhi vessels. Radiographic, angiographic and histological analyses were performed to assess bone and vessel formation. Tube formation, alkaline phosphatase (ALP) and Von Kossa staining assays were performed to test angiogenesis of endothelial precursor cells (EPCs) and osteogenesis of bone marrow‑derived mesenchymal stem cells (BMSCs). Additionally, expression levels of platelet‑derived growth factor (PDGF)‑BB, VEGF, runt‑related transcription factor 2 (RUNX2) and Osterix (OSX) were determined by western blotting and reverse transcription‑quantitative PCR. The in vivo assays demonstrated that TFRD markedly promoted CD31hiEmcnhi vessel formation during DO, whereas PDGF‑BB neutralizing antibody suppressed vessel formation. Furthermore, the ALP, Von Kossa staining and tube formation assays indicated that TFRD notably elevated the angiogenic capacity of EPCs and osteogenic capacity of BMSCs under stress conditions, which was significantly suppressed by blocking PDGF‑BB. The protein and mRNA levels of PDGF‑BB, VEGF, RUNX2 and OSX were upregulated by TFRD, but downregulated by blocking PDGF‑BB. Thus, TFRD could facilitate CD31hiEmcnhi vessel formation and subsequently enhance angiogenic‑osteogenic coupling to regenerate bone defects during DO via the PDGF‑BB/VEGF/RUNX2/OSX signaling axis, which indicated that CD31hiEmcnhi vessels could be a potential novel therapeutic target for DO, and TFRD may represent a promising drug for promoting bone regeneration in DO by increasing CD31hiEmcnhi vessels.
研究领域:
药理学
·
骨科
·
分子生物学
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2022
·Vol. 12
·期 1
·2201661
·
IF 11.092
Zonghan Xu,Liang Wu,Yu Tang,Kun Xi,Jincheng Tang,Yichang Xu,Jingzhi Xu,Jian Lu,Kaijin Guo,Yong Gu,Liang Chen
The bone immune microenvironment (BIM) regulates bone regeneration and affects the prognosis of fractures. However, there is currently no effective strategy that can precisely modulate macrophage polarization to improve BIM for bone regeneration. Herein, a hybridized biphasic bionic periosteum, inspired by the BIM and functional structure of the natural periosteum, is presented. The gel phase is composed of genipin-crosslinked carboxymethyl chitosan and collagen self-assembled hybrid hydrogels, which act as the “dam” to intercept IL-4 released during the initial burst from the bionic periosteum fiber phase, thus maintaining the moderate inflammatory response of M1 macrophages for mesenchymal stem cell recruitment and vascular sprouting at the acute fracture. With the degradation of the gel phase, released IL-4 cooperates with collagen to promote the polarization towards M2 macrophages, which reconfigure the local microenvironment by secreting PDGF-BB and BMP-2 to improve vascular maturation and osteogenesis twofold. In rat cranial defect models, the controlled regulation of the BIM is validated with the temporal transition of the inflammatory/anti-inflammatory process to achieve faster and better bone defect repair. This strategy provides a drug delivery system that constructs a coordinated BIM, so as to break through the predicament of the contradiction between immune response and bone tissue regeneration.
研究领域:
组织工程
·
再生医学
·
免疫学
·
生物医学工程
·
骨生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBON
·
2018
·
IF 7.082
Jingwen Gao,Huiwen Xiong,Wei Zhang,Ying Wang,Hangxing Wang,Wei Wen,Xiuhua Zhang,Shengfu Wang
Here, an electrochemiluminescent aptasensor based on β-cyclodextrin/graphitic carbon nitride (β-CD/g-C 3 N 4 ) composite for selective and highly ultrasensitive assay of platelet derived growth factor BB (PDGF-BB) is fabricated. To achieve the sensitive and specific detection of PDGF-BB, it is an available strategy to explore excellent electrochemiluminescent (ECL) luminophores with the advantages of high electrochemical-driven luminescent activity and a specific recognition function. In this work, for the first time a novel β-CD non-covalently functionalized g-C 3 N 4 composite β-CD/g-C 3 N 4 was employed to construct the ECL detection platform for PDGF-BB based on its aptamer. The limit of detection was determined to be as low as 2.6 × 10 −13 g/mL. It was observed that β-CD was playing a key role in improving the adamantane-labeled DNA amount modified on the electrode surface. It can further help to amplify the ECL quenching effect by both energy transfer and photo-excited electron transfer processes between g-C 3 N 4 emitter and ferrocene quencher. It is anticipated that β-CD/g-C 3 N 4 may be a class of promising material for constructing ECL sensors.
研究领域:
分析化学
·
生物传感器
·
材料科学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Bio Materials
·
2024
·
IF 4.6
Juan Zhou,Yanling Zhao,Yan Ling,Peng Zhao,Hui Gao,Yang Yang,Jinghua Chen
By recruiting stem cells into scaffolds and differentiating them into osteoblasts, stem cells can be mobilized to directly repair bone defects, which avoids a series of disadvantages of exogenous stem cell implantation. In this study, a microsphere-composite hydrogel for the recruitment and osteogenic differentiation of stem cells was constructed. Methacrylic anhydride modified gelatin (GelMA) and heparin (HepMA), as well as nanohydroxyapatite (nHAP), were used to prepare microspheres followed by adsorbing platelet-derived growth factor BB (PDGF-BB) whose loading efficiency was 53.7 ± 2.2%. Then the microspheres were compounded to the GelMA hydrogel encapsulated with simvastatin (SIM) to obtain microsphere-composite hydrogel GHnH-P@GS. GHnH-P@GS hydrogel could slowly release SIM and PDGF-BB, and the extents of release within 7 days were 44.1 ± 2.0% and 32.8 ± 1.1%. The synergistic effect of small molecule drugs and growth factors not only induced the recruitment of rabbit bone marrow-derived mesenchymal stem cells, but also promoted the osteogenic differentiation of stem cells, which was confirmed by experiments of cell migration, alkaline phosphatase, and alizarin red staining. Collectively, the microsphere-composite hydrogel GHnH-P@GS has a certain reference significance for the design of scaffolds for alveolar bone repair and regeneration.
研究领域:
组织工程
·
再生医学
·
生物医学材料
·
干细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2019
·
IF 9.518
Rui Zhang,Na Lu,Jiaxing Zhang,Ruohong Yan,Jie Li,Lihua Wang,Na Wang,Min Lv,Min Zhang
In enzyme-based immunoassys, the use of natural enzyme has been remarkably restricted by the inconvenience in preparation and storage, especially for point-of-care testing. Nanozymes, which can mimic the functions of natural enzymes, have been regarded as promising alternatives due to their robust stability and convenience in fabrication. Here we fabricated one-dimensional Fe 3 O 4 @C core-shell nanostructures via a solvent-thermal method. Thus prepared nanocomposites showed excellent peroxidase-like activity, capable of catalyzing chromogenic substrates into colored products in the presence of H 2 O 2 . We then developed a nanozyme-linked aptamer sorbent assay (NLASA) in a sandwich format, in which the as-prepared Fe 3 O 4 @C nanowires were employed as catalytic labels for colorimetric detection by naked eyes. In the detection of platelet-derived growth factor BB (PDGF-BB), this assay reliably exhibited detection limits as low as 10 fM, with a working range from 10 fM to 100 nM. By incorporating G-quadruplex-hemin DNAzyme with Fe 3 O 4 @C nanowires, the detection limit could be further lowered to 50 aM. The detection limit of PDGF-BB in 50% human serum was 100 fM. This ultrasensitive, cost-effective and easy-to-operate sensing platform offers new opportunities for protein detection in clinical diagnosis.
研究领域:
生物化学
·
纳米技术
·
分析化学
·
临床诊断
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Jiayuan Wang,Huan Wang,Yong Wang,Zhao Liu,Zexi Li,Jiaying Li,Qixin Chen,Qingchen Meng,Wenmiao Will Shu,Junxi Wu,Can Xiao,Fengxuan Han,Bin Li
In bone tissue engineering, vascularization is one of the critical factors that limit the effect of biomaterials for bone repair . While various approaches have been tried to build vascular networks in bone grafts, lack of endothelialization still constitutes a major technical hurdle. In this study, we have developed a facile technique to fabricate endothelialized biomimetic microvessels (BMVs) from alginate-collagen composite hydrogels within a single step using microfluidic technology. BMVs with different sizes could be readily prepared by adjusting the flow rate of microfluids. All BMVs supported perfusion and outward penetration of substances in the tube. Endothelial cells could adhere and proliferate on the inner wall of tubes. It was also found that the expression of CD31 and secretion of BMP-2 and PDGF-BB were higher in the rat umbilical vein endothelial cells (RUVECs) in BMVs than those cultured on hydrogel. When co-cultured with bone marrow mesenchymal stem cells (BMSCs), endothelialized BMVs promoted the osteogenic differentiation of BMSCs compared to those in acellular BMV group. In vivo , markedly enhanced new bone formation was achieved by endothelialized BMVs in a rat critical-sized calvarial defect model compared to those with non-endothelialized BMVs or without BMVs. Together, findings from both in vitro and in vivo studies have proven that endothelialized BMVs function to facilitate osteogenesis and promote bone regeneration , and therefore might present an effective strategy in bone tissue engineering. Statement of significance In bone tissue engineering, limited vascularization is one of the critical factors that limit the effect of biomaterials for bone repair. In this study, we developed a facile technique to fabricate endothelialized biomimetic microvessels (BMVs) from alginate-collagen composite hydrogels within a single step using microfluidic technology. Both in vitro and in vivo studies have proven that endothelialized BMVs function to facilitate osteogenesis and promote bone regeneration, and therefore might present an effective strategy in bone tissue engineering.
研究领域:
组织工程
·
生物医学工程
·
再生医学
·
骨生物学
·
微流控技术
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 18
·2954-2961
·
IF 5.047
Wenbing Wan,Feng Cai,Jiayu Huang,Shixuan Chen,Qi Liao
Diabetic wounds are characterized by sustained chronic inflammation, and decreased granulation tissue formation and vascularization, and it is a great challenge for researchers to promote chronic wound healing. In this study, we fabricate a bilayer skin substrate composed of a top layer made of silver-loaded gelatine cryogel and a bottom layer made of a platelet-derived growth factor-BB (PDGF-BB) loaded 3D printed gelatine scaffold for diabetic wound healing. In vitro, the concentration of loaded silver has no effect on the proliferation of fibroblasts, keratinocytes and immune cells cocultured with silver-loaded 3D bilayer hydrogel extract medium. In addition, the CFU quantification results showed that the release of silver nanoparticles was able to significantly kill bacteria including Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli. In vivo, PDGF-BB-loaded scaffolds, and silver and PDGF-BB coloaded scaffolds were able to accelerate wound closure, re-epithelialization, granulation tissue formation and angiogenesis compared to the scaffold and silver-loaded scaffold groups at each indicated time point. The silver and PDGF-BB coloaded bilayer hydrogel scaffolds show great potential for promoting diabetic wound healing and against bacterial infections.
研究领域:
生物医学工程
·
组织工程
·
伤口愈合
·
感染控制
✓ 已验证
DOI
高影响因子
Stem Cell Research & Therapy
·
2022
·Vol. 13
·期 1
·1-16
·
IF 8.079
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.
研究领域:
细胞生物学
·
分子生物学
·
血管生物学
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）