Advanced Science
·
2023
·
IF 15.1
Dan Li,Yucan Jiang,Ping He,Yeming Li,Yan Wu,Wei Lei,Nanxin Liu,Joost D. de Bruijn,Hua Zhang,Hongmei Zhang,Ping Ji,Huipin Yuan,Mingzheng Li
Heterotopic ossification (HO) is a double-edged sword. Pathological HO presents as an undesired clinical complication, whereas controlled heterotopic bone formation by synthetic osteoinductive materials shows promising therapeutic potentials for bone regeneration. However, the mechanism of material-induced heterotopic bone formation remains largely unknown. Early acquired HO being usually accompanied by severe tissue hypoxia prompts the hypothesis that hypoxia caused by the implantation coordinates serial cellular events and ultimately induces heterotopic bone formation in osteoinductive materials. The data presented herein shows a link between hypoxia, macrophage polarization to M2, osteoclastogenesis, and material-induced bone formation. Hypoxia inducible factor-1 α (HIF-1 α ), a crucial mediator of cellular responses to hypoxia, is highly expressed in an osteoinductive calcium phosphate ceramic (CaP) during the early phase of implantation, while pharmacological inhibition of HIF-1 α significantly inhibits M2 macrophage, subsequent osteoclast, and material-induced bone formation. Similarly, in vitro, hypoxia enhances M2 macrophage and osteoclast formation. Osteoclast-conditioned medium enhances osteogenic differentiation of mesenchymal stem cells, such enhancement disappears with the presence of HIF-1 α inhibitor. Furthermore, metabolomics analysis reveals that hypoxia enhances osteoclastogenesis via the axis of M2/lipid-loaded macrophages. The current findings shed new light on the mechanism of HO and favor the design of more potent osteoinductive materials for bone regeneration.
研究领域:
生物材料
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骨生物学
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组织工程
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Research
·
2025
·
IF 9.6
Shenhui Ren,Junchao Liu,Hongji Pu,Penghui Wang,Xiaodong Wu,Jinbao Qin,Xiaobing Liu,Minyi Yin,Xinwu Lu,Bo Li,Zhen Zhao
Atherosclerosis is the leading cause of global cardiovascular morbidity and mortality associated with inflammatory and immunological mechanisms. Immunotherapy has demonstrated promising efficacy in the management of atherosclerosis. Nevertheless, certain immunotherapeutic approaches are associated with limitations, including suboptimal efficacy and non-negligible adverse effects. Upon the pivotal role of macrophage phenotypes in atherosclerosis progression, naringenin-loaded manganese-doped mesoporous silica nanoparticles (MMSN@NAR) were designed and synthesized to reprogram M1 macrophages toward the M2 phenotype, thereby offering a potential therapeutic strategy for atherosclerosis treatment. High loading capacity of naringenin was achieved in MMSN carriers, with superior biocompatibility profiles compared to naringenin dissolved in dimethyl sulfoxide, while maintaining pH-dependent release behavior as demonstrated by dialysis assays. MMSN@NAR is preferentially phagocytosed by M1 macrophages, attenuates inflammatory responses, protects against oxidative stress, and promotes M2 polarization via the AMP-activated protein kinase (AMPK) pathway in vitro. In the ApoE −/− mouse unilateral carotid artery ligation model of atherosclerosis, MMSN@NAR demonstrated marked accumulation in plaques and excellent biocompatibility. Compared to using naringenin or MMSN alone, it could further reduce plaque area by approximately 40% or 60% by inducing macrophage phenotype transformation, which was confirmed by section staining and immunofluorescence. Collectively, this study highlights enhanced macrophage M2 polarization inhibiting atherosclerosis by MMSN@NAR as a promising nanoplatform, offering a novel therapeutic approach based on anti-inflammatory immune regulation.
研究领域:
纳米医学
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免疫治疗
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心血管疾病
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药物递送
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炎症研究
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生物化学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2021
·
IF 7.561
Li Qiuju,Yuan Ming,Jiao Xue,Huang Yufei,Li Jing,Li Dong,Ji Miaomiao,Wang Guoyun
Background: Endometriosis is a common nonmalignant gynecological disorder that affects 10–15% women of reproductive age and causes several symptoms that result in decreased quality of life and a huge social burden. In recent decades, extracellular vesicles (EVs) have gained attention as a potential therapeutic tool; however, the therapeutic effects of EVs against endometriosis have not been reported. Accordingly, in this study, we investigated the feasibility of nanovesicles (NVs) derived from M1 macrophages (M1NVs) in treating endometriosis.Methods: M1NVs were prepared by serial extrusion. Co-culture assays were performed to investigate changes in tube formation and migration/invasion of eutopic endometrial stroma cells (ESCs) obtained from patients with endometriosis (EM-ESCs). A mouse model of endometriosis was established, and mice were treated with phosphate-buffered saline, M0NVs, or M1NVs to evaluate the efficacy and safety of M1NV for treating endometriosis.Results: M1NVs directly or indirectly inhibited the migration and invasion of EM-ESCs and reduced tube formation. In the mouse model, M1NVs suppressed the development of endometriosis through reprogramming of M2 macrophages, without causing damage to the organs.Conclusions: M1NVs inhibit the development of endometriosis directly, or through repolarizing macrophages from M2 to M1 phenotype. Hence, administration of M1NVs may represent a novel method for the treatment of endometriosis.
研究领域:
妇科学
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免疫学
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纳米技术
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Hao Meng,Jianlong Su,Qi Shen,Wenzhi Hu,Pinxue Li,Kailu Guo,Xi Liu,Kui Ma,Weicheng Zhong,Shengqiu Chen,Liqian Ma,Yaying Hao,Junli Chen,Yufeng Jiang,Linlin Li,Xiaobing Fu,Cuiping Zhang
Chronic diabetic wounds are characterized by prolonged inflammation and excessive accumulation of M1 macrophages, which impede the healing process. Therefore, resolving inflammation promptly and transitioning to the proliferative phase are critical steps for effective diabetic wound healing. Exosomes have emerged as a promising therapeutic strategy. In this study, a smart hydrogel capable of responding to pathological cues in the inflammatory microenvironment to promote the transition from inflammation to proliferation by delivering M2 macrophage-derived exosomes (M2-Exos) is developed. The smart hydrogel is synthesized through the cross–linking of oxidized dextran, a matrix metalloproteinase (MMP)-9-sensitive peptide, and carboxymethyl chitosan containing M2-Exos. In response to elevated MMP-9 concentrations in the inflammatory microenvironment, the hydrogel demonstrates diagnostic logic, adjusting the release kinetics of M2-Exos accordingly. The on-demand release of M2-Exos facilitated macrophage polarization from the M1 to the M2 phenotype, thereby promoting the transition from the inflammatory to the proliferative phase and accelerating diabetic wound healing. The transcriptomic analysis further reveals that the MMP-9-responsive hydrogel with M2-Exos delivery exerts anti-inflammatory and regenerative effects by downregulating inflammation-related pathways. This study introduces an innovative, microenvironment-responsive exosome delivery system that enables precise control of therapeutic agent release, offering a personalized approach for the treatment of chronic diabetic wounds.
研究领域:
生物医学工程
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组织工程
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伤口愈合
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药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Qi Wang,Jiaxin Dong,Mengxian Du,Xinna Liu,Shiqi Zhang,Di Zhang,Wanyun Qin,Xikun Xu,Xianghui Li,Ruidong Su,Leyi Qiu,Baoqiang Li,Huiping Yuan
Introduction: Glaucoma is a prevalent cause of irreversible vision impairment, characterized by progressive retinal ganglion cells (RGCs) loss, with no currently available effective treatment. Rapamycin (RAPA), an autophagy inducer, has been reported to treat glaucoma in rodent models by promoting RGC survival, but its limited water solubility, systemic toxicity, and pre-treatment requirements hinder its potential clinical applications.Methods: Chitosan (CS)-RAPA carbon dot (CRCD) was synthesized via hydrothermal carbonization of CS and RAPA and characterized by transmission electron microscopy, Fourier transform infrared spectra, and proton nuclear magnetic resonance. In vitro assays on human umbilical cord vein endothelial and rat retinal cell line examined its biocompatibility and anti-oxidative capabilities, while lipopolysaccharide-stimulated murine microglia (BV2) assays measured its effects on microglial polarization. In vivo, using a mouse retinal ischemia/reperfusion (I/R) model by acute intraocular pressure elevation, the effects of CRCD on visual function, RGC apoptosis, oxidative stress, and M2 microglial polarization were examined.Results: CRCD exhibited good water solubility and anti-oxidative capabilities, in the form of free radical scavenging. In vitro, CRCD was bio-compatible and lowered oxidative stress, which was also found in vivo in the retinal I/R model. Additionally, both in vitro with lipopolysaccharide-stimulated BV2 cells and in vivo with the I/R model, CRCD was able to promote M2 microglial polarization by activating autophagy, which, in turn, down-regulated pro-inflammatory cytokines, such as IL-1β and TNF-α, as well as up-regulated anti-inflammatory cytokines, such as IL-4 and TGF-β. All these anti-oxidative and anti-inflammatory effects ultimately aided in preserving RGCs, and subsequently, improved visual function.Discussion: CRCD could serve as a potential novel treatment strategy for glaucoma, via incorporating RAPA into CDs, in turn not only mitigating its toxic side effects but also enhancing its therapeutic efficacy.
研究领域:
眼科
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药学
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神经科学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Yang Yuan,Daidi Fan,Shihong Shen,Xiaoxuan Ma
At present, approximately 19–34% of diabetic patients (nearly 450 million) may have complications involving diabetic foot ulcers (DFUs). Wound healing of DFUs still faces huge problems, such as long-term chronic inflammation and impaired angiogenesis . Therefore, an M2 macrophage-polarized anti-inflammatory hydrogel (HTHE-M@D) combined with mild heat stimulation is designed for DFUs treatment. The HTHE-M@D hydrogel is prepared by enzymatic cross-linking of epigallocatechin gallate dimer-grafted hyaluronic acid (HA-EGCG) and tyramine-grafted human-like collagen (HLC-TA) and integrating deferoxamine-loaded mesoporous polydopamine nanoparticles (M@D). The hydrogel exhibits prominent enhancement of angiogenesis, which is attributed to the combination of mild heat stimulation via photothermal effects and the angiogenic drugs (deferoxamine) released from the hydrogel. The hydrogel also promotes the transformation of macrophages from the M1 to M2 phenotype and exhibits good anti-inflammatory, antibacterial, antioxidant, hemostatic properties and biocompatibility. Additionally, the hydrogel has desirable mechanical strength, enhanced tissue adhesion and injectability, thus making it more adaptive to DFUs. The results demonstrate that the combination of the hydrogel and mild thermal stimulation promotes skin regeneration of diabetic wounds and shortens the healing time to 13 days. The combined treatment might offer a promising therapeutic strategy for DFUs.
研究领域:
生物医学工程
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糖尿病研究
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组织修复与再生
✓ 已验证
产品关联
DOI
高影响因子
Materials Today Bio
·
2023
·
IF 8.2
Qing Zhang,Mengyu Xin,Shuang Yang,Qiuyu Wu,Xi Xiang,Tianqi Wang,Wen Zhong,Marco N. Helder,Richard T. Jaspers,Janak Lal Pathak,Yin Xiao
Targeting macrophages to regulate the immune microenvironment is a new strategy for bone regeneration with nano-drugs. Nano-drugs have achieved surprising anti-inflammatory and bone-regenerative effects, however, their underlying mechanisms in macrophages remain to be clarified. Macrophage polarization, immunomodulation, and osteogenesis are governed by autophagy. Rapamycin, an autophagy inducer, has shown promising results in bone regeneration, but high dose-mediated cytotoxicity and low bioavailability hinder its clinical application. This study aimed to develop rapamycin-loaded virus-like hollow silica nanoparticles ( [email protected] ) which are easily phagocytosed by macrophages and translocated to lysosomes. [email protected] induced macrophage autophagy, promoted M2 polarization, and alleviated the degree of M1 polarization as indicated by the downregulation of inflammatory factors IL-6, IL-1β, TNF-α, and iNOS, and upregulation of anti-inflammatory factors CD163, CD206, IL-1ra, IL-10, and TGF-β. These effects were nullified by cytochalasin B-induced inhibition of [email protected] uptake in macrophages. The conditioned medium (CM) collected from [email protected] macrophages promoted osteogenic differentiation of mouse bone marrow mesenchymal stromal cells (mBMSCs). In a mouse calvaria defect model, free rapamycin treatment was inhibited, but [email protected] robustly promoted bone defect healing. In conclusion, silica nanocarrier-mediated intracellular rapamycin delivery to macrophages effectively triggers autophagy-mediated M2 macrophage polarization, further enhancing bone regeneration by triggering osteogenic differentiation of mBMSCs.
研究领域:
纳米医学
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免疫学
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骨再生
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药理学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Research
·
2023
·
IF 9.9
Wu Guanghao,Mu Changwen,Zhao Qianru,Lei Yao,Cheng Ran,Nie Weidong,Qu Jiamin,Dong Yuping,Yang Ruili,Xie Haiyan
Atherosclerosis is the most common cause of cardiovascular diseases that contribute to the major morbidity worldwide, but still lacking of effective treatment strategy. Here, a hybrid cell is constructed for the sonodynamic effect promoted cell therapy of early atherosclerosis by fusing M2 macrophages with thylakoid (TK) membranes. After systemic administration, the obtained TK-M2 actively accumulates in the early atherosclerotic plaques, wherein M2 macrophages relieve the cholesterol accumulation and the inflammation in the foam cells. Meanwhile, the TK membranes decorated on the M2 macrophages exhibit both type I and type II sonodynamic effects under ultrasound (US) activation, inducing the direct apoptosis of foam cells. The cooperation of M2 and TK leads to significant outcome in eliminating atherosclerotic plaques without obvious side-effects, providing a new avenue for atherosclerosis treatment.
研究领域:
心血管疾病
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细胞治疗
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生物医学工程
·
超声治疗
✓ 已验证
DOI
高影响因子
MOLECULAR THERAPY
·
2024
·
IF 12.1
Xiaoyuan Huang,Yanhua Lan,Jiahui Shen,Xiaomin Zhao,Yanyan Zhou,Wenzhi Wu,Jiajie Mao,Yuzhu Wu,Zhijian Xie,Zhuo Chen
Osteoclast precursors (OCPs) are thought to commit to osteoclast differentiation, which is accelerated by aging-related chronic inflammation, thereby leading to osteoporosis. However, whether the fate of OCPs can be reshaped to transition into other cell lineages is unknown. Here, we showed that M2 macrophage-derived extracellular vesicles (M2-EVs) could reprogram OCPs to downregulate osteoclast-specific gene expression and convert OCPs to M2 macrophage-like lineage cells, which reshaped the fate of OCPs by delivering the molecular metabolite glutamate. Upon delivery of glutamate, glutamine metabolism in OCPs was markedly enhanced, resulting in the increased production of α-ketoglutarate (αKG), which participates in Jmjd3-dependent epigenetic reprogramming, causing M2-like macrophage differentiation. Thus, we revealed a novel transformation of OCPs into M2-like macrophages via M2-EVs-initiated metabolic reprogramming and epigenetic modification. Our findings suggest that M2-EVs can reestablish the balance between osteoclasts and M2 macrophages, alleviate the symptoms of bone loss, and constitute a new approach for bone-targeted therapy to treat osteoporosis.
研究领域:
免疫学
·
细胞生物学
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代谢研究
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骨骼研究
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Zhenhui Liao,Lu Liang,Hao Fang,Yumei Cui,Cun Liang,Guobin Huang,Zichao Dai,Zijun Song,Hefeng Yang,Jinhui Huang
Manipulating the immune microenvironment (including the macrophage phenotype) by tissue implants is an important direction in the field of tissue regeneration. This study reports a macrophage-loaded hybrid scaffold construction to improve the response efficiency of implant–macrophage–tissue regeneration axis and precisely polarize macrophages toward the pro-regenerative M2 phenotype in vitro, and constructed an M2 macrophage-loaded hybrid scaffold. The feasibility of using a macrophage-loaded hybrid scaffold for immune-mediated periodontal regeneration is studied in vivo and in vitro. The results illustrate that the M2 macrophage-loaded hybrid scaffolds promoted the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro and promoted cell recruitment and angiogenesis in vivo to perform well in early in vivo osteogenesis. The macrophage-loaded hybrid scaffold proposed in this study plays an important role in promoting periodontal regeneration, which enriches the theory and strategy of macrophage phenotype regulation-mediated periodontal regeneration, and provides inspiration and reference for using macrophage-loaded hybrid scaffolds in regenerating other tissues.
研究领域:
组织工程
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免疫学
·
牙科医学
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再生医学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Polymer Materials
·
2023
·
IF 5
Yiwen Pan,Shaoqing Chen,Yanyan Meng,Mu He,Chun Liu,Cheli Wang,Xinye Ni
The treatment of bone defects caused by diseases, trauma, or tumor has always been a great clinical challenge. Implantation of bone biomaterials into bone defect areas is an effective method for bone injury repair. In this study, we used three-dimensional (3D) printing technology to prepare nano-hydroxyapatite (nHA)/sodium alginate (SA)/gelatin (Gel) hydrogel scaffolds loaded with different ratios (0, 0.13, 0.26, 0.39, 0.53, and 0.79‰) of emodin (EM) (EM/nHA/SA/Gel). Scanning electron microscopy showed that the scaffolds had a smooth surface without fracture and nHA was evenly distributed on the surface. The cell proliferation and migration results showed that the 0.39‰ EM group, in particular, could significantly promote the proliferation and migration of mouse embryonic osteoblast precursor (MC3T3-E1) cells and significantly increase the mRNA expression of osteogenic differentiation-related genes (bone morphogenetic protein/BMP-2, BMP-9, osteocalcin). In addition, the 0.39‰ EM group exhibited the best effect on osteogenic differentiation-related proteins (alkaline phosphatase, Runx 2, OSX). The expression of M2 polarization-related genes (arginase-1, CD206) also significantly increased after the treatment with the 0.39‰ EM group. Micro-CT showed that in the rat skull defect model, the EM/nHA/SA/Gel scaffold group significantly promoted bone regeneration after being implanted into the skull for 30 days. Our results indicate that the EM/nHA/SA/Gel hydrogel scaffolds can not only directly promote the proliferation and differentiation of osteoblasts but also indirectly promote osteogenic differentiation by supporting M2 polarization of macrophages. EM/nHA/SA/Gel hydrogel scaffolds are potential bone tissue engineering materials for bone regeneration.
研究领域:
生物医学工程
·
组织工程
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骨科
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Renhao Ni,Yang Luo,Lingjing Jiang,Xufeng Mao,Yuyao Feng,Subinuer Tuersun,Zeming Hu,Yabin Zhu
The treatment of gastric ulcer and perforation using synthetic and biomaterials has been a clinical challenge. In this work, a drug-carrying layer of hyaluronic acid was combined with a gastric submucosal decellularized extracellular matrix called gHECM. The regulation of macrophage polarization by the extracellular matrix's components was then investigated. This work proclaims how gHECM responds to inflammation and aids in the regeneration of the gastric lining by altering the phenotype of surrounding macrophages and stimulating the body's whole immune response. In a nutshell, gHECM promotes tissue regeneration by changing the phenotype of macrophages around the site of injury. In particular, gHECM reduces the production of pro-inflammatory cytokines, decreases the percentage of M1 macrophages, and further encourages differentiation of macrophage subpopulation to the M2 phenotype and the release of anti-inflammatory cytokines, which could block the NF-κB pathway. Activated macrophages are capable of immediately delivering through spatial barriers, modulating the peripheral immune system, influencing the inflammatory microenvironment, and ultimately promoting the recovery of inflammation and healing of ulcers. They contribute to the secreted cytokines that act on local tissues or enhance the chemotactic ability of macrophages through paracrine secretion. In this study, we focused on the immunological regulatory network of macrophage polarization to further develop the mechanisms behind this process. Nevertheless, the signaling pathways involved in this process need to be further explored and identified. We think that our research will encourage more investigation into how the decellularized matrix affects immune modulation and will help the decellularized matrix perform better as a new class of natural biomaterials for tissue engineering.
研究领域:
组织工程
·
免疫学
·
胃肠病学
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生物材料
✓ 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）