Bioactive Materials
·
2024
·
IF 18
An Shao,Lulu Jin,Yanni Ge,Ziqiang Ye,Mingyu Xu,Yifan Zhou,Yingyu Li,Linyan Wang,Pinglong Xu,Kai Jin,Zhengwei Mao,Juan Ye
Retinal neovascularization (RNV), a typical pathological manifestation involved in most neovascular diseases, causes retinal detachment, vision loss, and ultimately irreversible blindness. Repeated intravitreal injections of anti-VEGF drugs were developed against RNV, with limitations of incomplete responses and adverse effects. Therefore, a new treatment with a better curative effect and more prolonged dosage is demanding. Here, we induced macrophage polarization to anti-inflammatory M2 phenotype by inhibiting cGAS-STING signaling with an antagonist C176, appreciating the role of cGAS-STING signaling in the retina in pro-inflammatory M1 polarization. C176-loaded and phosphatidylserine-modified dendritic mesoporous silica nanoparticles were constructed and examined by a single intravitreal injection. The biosafe nanoparticles were phagocytosed by retinal macrophages through a phosphatidylserine-mediated “eat me” signal, which persistently release C176 to suppress STING signaling and thereby promote macrophage M2 polarization specifically. A single dosage can effectively alleviate pathological angiogenesis phenotypes in murine oxygen-induced retinopathy models. In conclusion, these C176-loaded nanoparticles with enhanced cell uptake and long-lasting STING inhibition effects might serve as a promising way for treating RNV.
研究领域:
眼科学
·
纳米技术
·
免疫学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2016
·
IF 3.902
Hao Chang,He Zhang,Mi Hu,Jia-yan Chen,Bo-chao Li,Ke-feng Ren,M.Cristina L. Martins,Mário A. Barbosa,Jian Ji
Endothelialization has proved to be critical for maintaining long-term success of implantable vascular devices. The formation of monolayer of endothelial cells (ECs) on the implant surfaces is one of the most important factors for the endothelialization. However, endothelial function of regenerated EC monolayer, which plays a much more important role in preventing the complications of post-implantation, has not received enough attention. Here, a vascular endothelial growth factor (VEGF)-incorporated poly( l -lysine)/hyaluronan (PLL/HA) polyelectrolyte multilayer film was fabricated. Through varying the crosslinking degree, stiffness of the film was manipulated, offering either soft or stiff film. We demonstrated that ECs were able to adhere and proliferate on both soft and stiff films, subsequently forming an integrated EC monolayer. Furthermore, endothelial functions were evaluated by characterizing EC monolayer integrity, expression of genes correlated with the endothelial functions, and nitric oxide production. It demonstrated that EC monolayer on the soft film displayed higher endothelial function compared to that on the stiff film. Our study highlights the influence of substrate stiffness on endothelial function, which offers a new criterion for surface design of vascular implants.
研究领域:
生物材料
·
组织工程
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Jintao Zhong,Wenhua Li,Hetong Li,Jin Zhang,Zuoxu Hou,Xiao Wang,Enhui Zhou,Ke Lu,Weida Zhuang,Hongxun Sang
The periosteum, a highly specialized thin tissue, is instrumental in contributing to as much as 70% of early bone formation. Recognizing the periosteum's vital physiological roles, the fabrication of a biomimetic periosteum has risen as an auspicious strategy for addressing extensive bone defects. In the study, we obtained such biomimetic periosteum by utilizing periosteum-derived stem cells (PDSCs) spheroids. These spheroids are induced to spontaneously generate a bioactive membrane on a delicate 3D-printed polycaprolactone (PCL) substrate. This process yields a biomimetic periosteum rich in the resources needed for bone repair. The in vitro evaluations demonstrated that this membrane can act as a repository for growth factors and stem cells. The release kinetics confirmed a sustained delivery of BMP-2 and VEGF, which promoted enhanced osteogenesis and angiogenesis in vitro , respectively. The in vivo results further highlighted robust bone regeneration from critical cranial defects upon the application of this biomimetic periosteum. The biomimetic periosteum, easily harvested and potent in bioactivity, presents substantial clinical potential, particularly for the treatment of critical-sized bone defects. Statement of Significance PDSC theoretically demonstrates substantial potential in membrane construction, a value we've harnessed in this pioneering application. By employing cell spheroids, we've successfully integrated a substantial number of cells into the membrane framework. PDSC spheroids exhibit the remarkable ability to self-assemble into functional membranes, endowing them with robust biological capabilities that enhance their performance in biological systems. The in vitro evaluations demonstrated that this membrane can act as a repository for growth factors and stem cells. The in vivo bone repair facilitated by this membrane is notably effective, characterized by superior bone quality and accelerated formation rates. This process mirrors the natural intramembrane ossification, offering a promising approach to bone integration and regeneration.
研究领域:
组织工程
·
再生医学
·
骨生物学
·
干细胞研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Yiming Ren,Liang Li
Probiotics have numerous biological functions and clinical studies have reported that consuming probiotic foods could promote hair growth and hair follicle health. Bifidobacterium longum BB536 was selected to investigate the possibility of treating hair loss with Cell-Free Supernatant (CFS) of B. longum BB536 and the alleviation mechanism of CFS on dihydrotestosterone (DHT)-damaged human dermal papilla cells (HDPCs). The results showed that HDPCs treated with 10% CFS of B. longum BB536 for 24 h could significantly promote cell proliferation, repair cell damage, accelerate the process of cell cycle and increase the secretion of VEGF. The CFS of B. longum BB536 reduced the apoptosis rate of DHT-damaged HDPCs. In addition, it could reduce the level of pro-inflammatory factors and improve the alkaline phosphatase (ALP) activity. Metabolites of B. longum BB536 may increase the protein expression of Wnt10b, β-catenin and LEF-1 by activating Wnt/β-catenin signaling pathway and inhibit the expression of DHT-induced negative feedback factors DKK1 and GSK-3β, which alleviates the damage of DHT on HDPCs, some protein expression levels such as LEF-1 are close to minoxidil (common drugs for hair loss). So, metabolites of B. longum BB536 can be used as new treatment for hair loss due to its safety. This study provides theoretical basis for probiotics to prevent androgenic alopecia.
研究领域:
微生物学
·
细胞生物学
·
药理学
·
皮肤病学
✓ 已验证
产品关联
DOI
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2024
·
IF 6.8
Siyue Chen,Yuming Liu,Yutian Zhang,Xu Guo,Tinghui Bai,Kai He,Yanfang Zhu,Yi Lei,Mei Du,Xiaohong Wang,Qiang Liu,Hua Yan
Background and Purpose Pathological retinal angiogenesis is a typical manifestation of vision-threatening ocular diseases. Many patients exhibit poor response or resistance to anti-vascular endothelial growth factor (VEGF) agents. Bruton's tyrosine kinase (BTK) controls the proliferation and function of immune cells. Therefore, we examined the anti-inflammatory and anti-angiogenic effects of BTK inhibition on retinal angiogenesis. Experimental Approach Retinal neovascularisation and vascular leakage in oxygen-induced retinopathy in C57/BL6J mice were assessed by whole-mount retinal immunofluorescence. PLX5622 was used to deplete microglia and Rag1 -knockout mice were used to test the contribution of lymphocytes to the effects of BTK inhibition. The cytokines, activation markers, inflammatory and immune-regulatory activities of retinal microglia/macrophages were detected using qRT-PCR and immunofluorescence. NLRP3 was detected by western blotting, and the effects of BTK inhibition on the co-culture of microglia and human retinal microvascular endothelial cells (HRMECs) were examined. Key Results BTK inhibition suppressed pathological angiogenesis and vascular leakage, and significantly reduced retinal inflammation, which involved microglia/macrophages but not lymphocytes. BTK inhibition increased anti-inflammatory factors and reduced pro-inflammatory cytokines that resulted from NLRP3 inflammasome activation. BTK inhibition suppressed the inflammatory activity of microglia/macrophages, and acted synergistically with anti-VEGF without retinal toxicity. Moreover, the supernatant of microglia incubated with BTK-inhibitor reduced the proliferation, tube formation and sprouting of HRMECs. Conclusion and Implications BTK inhibition suppressed retinal neovascularisation and vascular leakage by modulating the inflammatory activity of microglia and macrophages. Our study suggests BTK inhibition as a novel and promising approach for alleviating pathological retinal angiogenesis. Graphical
研究领域:
眼科学
·
免疫学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Jinwei Lin,Chenxi Lian,Leilei Xu,Zhengshang Li,Qiaoxin Guan,Wenying Wei,Honglian Dai,Jianguo Guan
Multifunctional nanoagents are robust to remodel environments for managing chronic diabetic wounds. However, their delivery primarily relies on Brownian motion and randomly enhanced diffusion. Here, taking advantage of wound heterogeneity, such as the uneven distribution of glucose, hyperglycemia targeting nanomotors are proposed. They are capable of efficiently targeting hyperglycemic interfaces in diabetic wounds for significantly accelerating their healing by employing endogenous glucose-activated cascade reactions and responding to local glucose gradients. Compared to previous counterparts, they show a four-fold enhancement in effective coverage within 60 s and a multiplied accumulation at hyperglycemic interfaces, facilitating deep penetration. Correspondingly, the downregulation of glucose levels is apparently enhanced, while pH-lowering and oxygen-supplying are both improved. In comparison to the counterparts delivered by passive diffusion and randomly enhanced diffusion, the hyperglycemia targeting nanomotor-based spray accelerates the wound healing upon diabetic mice by approximately 30% and 23%, resulting from the restricted inflammatory response, effective reactive oxygen species (ROS) scavenging and elevated vascular endothelial growth factor levels (VEGF). This study presents a generally efficient approach to facilitating the targeted delivery of nanoagents for the effective management of diabetic wounds by utilizing wound heterogeneity, which can be extended to other therapeutic systems.
研究领域:
纳米技术
·
生物医学工程
·
伤口愈合
·
糖尿病管理
✓ 已验证
产品关联
DOI
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-20
·
IF 14.7
Huang Zhusheng,Huang Shiqian,Song Simin,Ding Yankui,Zhou Hao,Zhang Shaoyin,Weng Lixing,Zhang Ying,Hu Yiqiao,Yuan Ahu,Dai Yunlu,Luo Zhimin,Wang Lianhui
The irradiated tumor itself represents an opportunity to establish endogenous in situ vaccines. However, such in situ cancer vaccination (ISCV) triggered by radiation therapy (RT) alone is very weak and hardly elicits systemic anticancer immunity. In this study, we develop two-dimensional risedronate-manganese nanobelts (RMn-NBs) as an adjuvant for RT to address this issue. RMn-NBs exhibit good T 2 magnetic resonance imaging performance and enhanced Fenton-like catalytic activity, which induces immunogenic cell death. RMn-NBs can inhibit the HIF-1α/VEGF axis to empower RT and synchronously activate the cGAS/STING pathway for promoting the secretion of type I interferon, thereby boosting RT-triggered ISCV and immune checkpoint blockade therapy against primary and metastatic tumors. RMn-NBs as a nano-adjuvant for RT show good biocompatibility and therapeutic efficacy, presenting a promising prospect for cancer radiotherapy and immunotherapy.
研究领域:
癌症研究
·
纳米技术
·
免疫治疗
·
放射治疗
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Polymeric Materials and Polymeric Biomaterials
·
2024
·
IF 2.5
Runzhi Xiang,Jialu Chen,Jiarui Dang,Hong Zhu,Zhihui Ran,Yuehan Dong,Xiangjie Wu,Yuran Yang,Huan Deng,Chengjie Xiong,Zhijun Huang,Peihu Xu,Wenjin Xu,Haixing Xu
Angiogenesis plays a crucial role in peripheral nerve regeneration after injury. We introduce a proangiogenic hydrogel-filled nerve conduit, designed to promote peripheral nerve regeneration. The hydrogel was synthesized by chemically crosslinking carboxylated silk fibroin (cSF) and chitosan (CS), enriched with vascular endothelial growth factor (VEGF) to initiate angiogenesis. Complementarily, a nerve conduit was fabricated using coaxial electrospinning of poly-lactic acid (PLA), silk fibroin (SF), and ibuprofen (IBU) was incorporated to further support nerve regeneration. The hydrogel exhibited optimal properties including rapid gelation, uniform porosity and full biodegradation within four weeks. The nerve conduit, on the other hand, displayed enhanced mechanical strength, elasticity, and controlled biodegradability. In vitro assays demonstrated a sustained release of VEGF and IBU, which significantly enhanced cell adhesion, proliferation, migration and angiogenesis in Human umbilical vein endothelial cells (HUVEC), as well as promoted adhesion and proliferation in rat Schwann cells (RSC96). This proangiogenic hydrogel-filled nerve conduit thus emerged as a potent candidate for advancing peripheral nerve regeneration.
研究领域:
组织工程
·
生物材料
·
神经科学
·
再生医学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
·
2018
·Vol. 18
·期 4
·2379-2386
·
IF 1.354
Gong Xiaojin,Zhao Qian,Song Mu,Xue Feng
In our study, we report on the design and characterization of a combined angiogenesis therapy for breast cancer based on well-formed amine-functionalized silica nanoparticles (SLNs). The aminefunctionalized SLNs was employed to simultaneously deliver angiostatin (ANG) plasmid and candesartan
(CD) to the same cancer cell. The well-formed ANG/CD/SLNs exhibited small particle size, reasonable positive charges, excellent loading of drug and gene in vitro. Moreover, aminefunctionalized SLNs were almost no cytotoxicity. ANG/CD/SLNs resulted in enhanced gene transfection compared
to naked plasmid. More importantly, ANG/CD/SLNs as a co-delivery system achieved a stronger inhibitory effect on angiogenesis in vitro, possibly resulting from significant downregulation of vascular endothelial growth factor (VEGF) expression via different pathways. In particular, in
vivo investigation on nude mice bearing MCF-7 xenografts confirmed that ANG/CD/SLNs codelivery system exerted strong anti-tumor efficacy by synergistic antiangiogenic mechanism.
研究领域:
纳米技术
·
癌症治疗
·
分子生物学
·
药剂学
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Xiang Wu,Fuxiao Wang,Ruiyang Li,Biao Yu,Tianhang Qi,Yunpeng Li,Xiao Chen,Jian Wang,Zhen Geng,Peiran Song,Long Bai,Dongyang Zhou,Hou-Feng Zheng,Qin Zhang,Jiacan Su
Conventional hydrogel drug delivery systems are limited in recapitulating the natural spatiotemporal progression of bone regeneration due to their passive release mechanisms. Here, an enzyme-responsive deoxyribonucleic acid (DNA)-polyethylene glycol (PEG) hydrogel is developed to actively coordinate the sequential processes of angiogenesis, osteogenesis, and mineralization through rational material design. The hydrogel integrates matrix metalloproteinase (MMP)-cleavable peptide-crosslinked PEG networks conjugated with actin-stabilized vascular endothelial growth factor (VEGF)-binding DNA strands, enabling spatiotemporally controlled therapeutic release. Upon implantation, MMPs trigger the hydrogel degradation, releasing VEGF to induce angiogenesis while simultaneously promoting osteogenic differentiation. The actin-stabilized DNA framework maintains structural integrity during this stage, preventing premature phosphate release. Subsequent matrix remodeling liberates nuclease that catalyzes DNA to generate phosphate ions, which synergize with peptides in hydrogels and endogenous calcium to drive mineralization. Molecular dynamics simulations reveal the underlying mechanism of hydrogel-mediated mineralization, demonstrating enhanced calcium phosphate formation. Such temporally controlled cascade significantly improves vascular density, osteogenic marker expression, and mineral deposition compared to controls. This work establishes a bioresponsive platform that dynamically interacts with the biological microenvironment to orchestrate multi-phase bone regeneration, offering new possibilities for complex tissue repair.
研究领域:
生物医学工程
·
组织工程
·
药物递送系统
·
生物材料
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Mengtian He,Dayang Xie,Qiannan Cao,Mingxia Jiang,Hongqian Liu,Yingli Yao,Wenming Zheng,Huilin Yuan,Pijun Su,Siting Zhang,Yuxuan He,Shuting Zeng,Yaqing Zeng,Huapan Fang,Hong Wu,Huayu Tian
Retinal neovascularization is one of the most prevalent fundus neovascular diseases, affecting vision and potentially leading to severe complications, such as retinal detachment or irreversible blindness. Current treatments primarily involve intravitreal injections (IVT) of anti-vascular endothelial growth factor (anti-VEGF) agents. However, such treatment often requires repeated injections, develop incomplete responses, and are associated with adverse effects. Therefore, novel therapeutic agents need to be developed that exhibit low side effects and improved therapeutic efficacy of retinal neovascularization. Herein, we develop a novel polymeric gene carrier, phenylboronic acid-modified linear polyethylenimine (LPEI-PBA) that is capable of loading plasmid expressing short hairpin RNA ( p shVEGF), which self-assembles with dexamethasone sodium phosphate (DSP) via electrostatic interactions to form a polymer-based gene-drug co-delivery system ( D SP/L P EI- P BA/ p sh V EGF, DPPV ) for combined neovascularization inhibition. DSP not only exerts anti-inflammatory effects but also enhances the transfection efficiency of LPEI-PBA. DPPV demonstrated favorable anti-neovascular effects both in vitro and in vivo . In an oxygen-induced retinopathy model, a single intravitreal administration of DPPV can significantly inhibited pathological neovascularization, accompanied by the downregulation of glial activation markers glial fibrillary acidic protein (GFAP) and ionized calcium-binding junction molecule 1 (IBA-1), as well as the pro-inflammatory factor interleukin-1β (IL-1β), and the upregulation of the anti-inflammatory factor ARG-1. In conclusion, DPPV nanoparticles effectively inhibit pathological retinal neovascularization through dual anti-inflammation and anti-angiogenesis, showing a promising therapeutic option for fundus neovascularization diseases.
研究领域:
纳米医学
·
基因治疗
·
眼科学
·
药物递送系统
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2022
·
IF 9.417
Lanjie Lei,Xiangguo Wang,Yulin Zhu,Wentao Su,Qizhuang Lv,Dong Li
Growth factors are vital to regulate cellular responses for wound healing process. Engineered microspheres provide a promising tool for developing effective growth factor-loaded matrix for regenerative medicine therapy. Here, we report a novel multifunctional chitosan microsphere that enables facile one-step capture and efficient growth factor delivery for enhanced wound repair. The microfluidic technique was used to fabricate magnetic chitosan (MCS) microspheres. By immobilization with Zn 2+ ions, the biohybrid MCS allowed for the flexible operation to capture histidine-tagged vascular endothelial growth factor (VEGF) produced in Escherichia coli (E. coli) . The VEGF-conjugated MCS were then applied onto the wounds to examine their capabilities in promoting wound healing. Zn 2+ and chitosan in MCS exhibited a synergetic antibacterial effect towards both Gram-positive and Gram-negative bacteria. Using a rat model, we further demonstrated that the microspheres significantly promoted wound healing process, as evidenced by rapid wound closure, induced epithelialization and angiogenesis, and reduced inflammation response. Together, our data indicated the presented MCS as a versatile tool for capturing and locally delivering growth factors, which can be applied to wound repair. Moreover, with the functional flexibility, this biohybrid MCS could be empolyed in a wide range of biomedical applications by conjugating proteins of interest.
研究领域:
再生医学
·
生物医学工程
·
伤口愈合
·
药物递送系统
·
组织工程
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）